Plabable 2020 Hematology Mfa

HAEMATOLOGY
Questions&Answers
Q-1
A 35 year old first time donor suddenly passes out as she is donating blood. She
is not known to have any medical problems in the past. Which of the following
steps would be the least useful in managing this adverse event?
A. Ensure donor is adequately hydrated and has not skipped a meal

B. Elevating the donor’s legs as this is usually due to a vasovagal syncope
C. Ensure haemoglobin of the donor meets the minimum requirements for
donation
D. The donation is continued along with simultaneous normal saline infusion
E. The donor should be encouraged to mobilise after they have recovered
ANSWER:
The donation is continued along with simultaneous normal saline infusion
EXPLANATION:
This question may seem tricky, but it is actually really simple. You need to read the
question well; it states, ‘which would be the LEAST useful in managing the adverse
event’
A is correct. Blood donors should ensure they are well hydrated and have eaten well
before donating blood.
B is correct. Elevation of the legs would cause more blood to return to the heart and
hence more blood to be pumped to the brain.
C is correct. People should not donate blood if their haemoglobin level is below the
lower limit of normal.
E is correct. The donor should be encouraged to eat, rest and continue their normal
activities as soon as possible after the donation.
This leaves us with D. If a donor faints whilst giving blood, YOU IMMEDIATELY STOP
THE DONATION. You should never continue bleeding the donor if an adverse event
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has occurred or is about to occur.
In general, you should not take more than 30 seconds to answer these types of
questions.
Q-2
A 13 year old girl has mucosal bleeding and petechial rashes. She has been
feeling tired lately. She looks pale. A blood count shows:
Haemoglobin 74 g/L
White cell count 1.9 x 109/L
Neutrophils 0.1 x 109/L
Platelets 24 x 109/L
Blood film morphology was unremarkable. Reticulocytes are absent. A bone

marrow aspirate shows a gross reduction in all haematopoietic tissue that is
replaced by fat spaces. What is the SINGLE most likely underlying diagnosis?
A. Pernicious anaemia
B. Chronic myeloid leukaemia
C. Aplastic anaemia
D. Acute myeloid leukaemia
E. Acute lymphoblastic leukaemia
ANSWER:
Aplastic anaemia
EXPLANATION:
She has signs and symptoms of anaemia. The blood picture showspancytopenia which
rules out pernicious anaemia as an underlying cause.
Normal morphology rules out the possibility of acute myeloid leukaemia,and acute
lymphoblastic leukaemia.
From the age alone we can exclude chronic myeloid leukaemia as it usuallypresents at
age 40 to 50 years old (middle-age)
A bone marrow aspirate that shows a gross reduction in all haemopoietictissue that is
replaced by fat spaces is seen classically in aplastic anaemia.Absent reticulocytes
support the diagnosis.
Aplastic anaemia
Aplastic anaemia is a rare, potentially life-threatening failure ofhaemopoiesis
characterised by pancytopenia and hypoplastic marrow (themarrow stops making cells).
Causes
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Most cases are autoimmune, triggered by drugs (viruses, eg parvovirus,hepatitis) or
irradiation.
Presentation
Aplastic anaemia can present abruptly over, or insidiously over, weeks tomonths.
Clinical manifestations are proportional to the peripheral-blood cytopeniasand include:
• Symptoms of anaemia (pallor, headache, palpitations, dyspnoea,fatigue, or ankle
oedema) Note: Anaemic symptoms are usually lesssevere due to the chronic onset
• Symptoms of thrombocytopenia (skin or mucosal haemorrhage,visual disturbance due
to retinal haemorrhage, petechial rashes)
• Infection (a less common presentation) particularly upper and lowerrespiratory tracts,
skin, mouth, and peri-anal
• There is no lymphadenopathy or hepatosplenomegaly (in theabsence of infection).
Diagnostic tests:
Marrow examination is needed for the diagnosis
Note: To define aplastic anaemia based on FBC and bone marrow findings,
at least two of the following must be present:
• Haemoglobin <10 g/dL
• Platelet count < 50 x 109/L
• Neutrophil count <1.5 x 109/L
It is also important to note that the blood film morphology is unremarkable

which differentiates it from some other types of leukaemias.
Q-3
A 5 year old child presents with fever and pallor. His parents say he always feels
tired and is not as active as the other children around his age. On examination,
splenomegaly was noted. Blood results show:
Hb 7 g/dL
WCC 2 x 109/L
What is the SINGLE most likely diagnosis?
A. Acute myeloid leukaemia

B. Acute lymphoblastic leukaemia
C. Chronic myeloid leukaemia
D. Chronic lymphocytic leukaemia
E. Hodgkin’s lymphoma
ANSWER:
Acute lymphoblastic leukaemia
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EXPLANATION:
Acute lymphoblastic leukaemia (ALL)
Aetiology
Most cases of acute leukaemia arise with no apparent cause. There areseveral well
known associations with the development of acute leukaemiathat are sometimes
present. These include radiation exposure,chemotherapeutic agents, as well as some
retroviruses.
Clinical Presentation
The most common presentation results from the effects of the leukaemicblast cells
crowding out the normal marrow cells, resulting in symptoms ofpancytopenia even if the
total white blood cell count is normal.
• Fatigue from anaemia is the most common presenting complaint.
• Bleeding, petechiae, purpura or ecchymoses (due tothrombocytopenia)
• Recurrent and severe infections (oral, throat, skin, perianalinfections commonly). This
is because of the underproduction orabnormal function of white blood cells.
• Left upper quadrant fullness and early satiety due to splenomegaly(10-20%)
Acute lymphocytic leukaemia (ALL) is more common in children, and

acutemyelogenous leukaemia (AML) is more common in adults, but they
areindistinguishable clinically. This means you cannot determine the diagnosisonly from
the clinical presentation.
ALL is more often associated with infiltration of other organs, but AML cando it as well.
Enlargement of the liver, spleen, and lymph nodes and bonepain are common at
presentation.
Diagnosis
The FBC is the first clue to the diagnosis. Depression of all three cell lines is
common at presentation.
FBC
• Anaemia is usual and Hb may be below 5 g/L
• The white cell count can be low, normal, or elevated
• Thrombocytopenia
Many other disorders can present as pancytopenia similar to leukaemiasuch as aplastic

anaemia, infections involving the marrow, metastaticcancer involving the marrow,
vitamin B12 deficiency, SLE, hypersplenism,and myelofibrosis. However, none of these
will have leukaemic blastscirculating in the peripheral blood. Although pancytopenia can
cause all ofthe above, in PLAB, when pancytopenia is in the options, it is
usuallyleukaemia, or aplastic anaemia.
A bone marrow biopsy showing numerous blasts confirms the diagnosis ofacute
leukaemia.
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It is very unlikely that the PLAB questions would ask you to differentiate theAML from
ALL using specific test. However, if a child (young age) is givenwith signs and
symptoms of pancytopenia, ALL would be the most likely asit is the commonest
childhood leukaemia.
Note:
• ALL is the commonest childhood leukaemia. Peak age is 2–4 yearsold.
• The Philadelphia chromosome occurs in 15–30% (mostly adults) andis associated
with a poor prognosis.
LEUKAEMIA COMPARISONS
ACUTE LEUKEMIAS
Acute Lymphoblastic Leukaemia (ALL) Acute Myeloid Leukaemia (AML)
• Fatigue from anaemia • Symptoms of anaemia
• Bleeding caused by thrombocytopenia • Bleeding caused by thrombocytopenia
• Recurrent and severe infections • Infection
• Splenomegaly • Gingivitis is common, with swollen,
bleeding gums
Acute lymphocytic leukaemia (ALL) is
more common in children, and acute FBC: Auer rods
myelogenous leukaemia (AML) is more Total WBC count is often high.
common in adults, but they are Neutrophils are usually depleted and blast
indistinguishable clinically cells are seen in their place
Bone marrow aspiration is the diagnostic
In the exam, when pancytopenia is in the procedure
options, it is usually leukaemia, or aplastic
anaemia. A bone marrow biopsy showing
numerous blasts confirms the diagnosis of
acute leukaemia
CHRONIC LEUKAEMIAS
Chronic Lymphocytic Leukaemia (CLL) Chronic Myeloid Leukaemia (CML)
CLL can often present as an asymptomatic Mnemonic: CML – Crazy Massive Large
elevation of white cells found on routine Spleen
evaluation of patients during investigations
for other health problems. These patients Usually presents at age 40 to 50 years old
are exclusively older (majority over 50 (middle-age)
years old)
• Fatigue (due to anaemia)
When patients do have signs and • Weight loss
symptoms they are usually non-specific • Night sweats
• Massive splenomegaly
When should you suspect CLL? • Gout due to rapid cell turnover
• Leukocytosis is common (often > 100
When an older patient has marked x 109/L
elevation in white cell count with marked
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lymphocytic predominance. The characteristic feature in CML is the
Ph chromosome, found in about 90% of
“Smudge cells” are seen on smear cases.
In the exam, look for massive

enlargement of spleen
Q-4
A 33 year old woman complains of tiredness for the last 3 months. On routine
blood test, she is found to have a haemoglobin of 85 g/L, low mean cell volume,
and low ferritin. What is the SINGLE most likely diagnosis?
A. Iron deficiency
B. Folate deficiency
C. Thalassaemia
D. Anaemia of chronic disease
E. Sideroblastic anaemia
ANSWER:
Iron deficiency
EXPLANATION:
The table below is a short summary of common findings given in the exam to help you
differentiate between the cause of the anaemia.
Microcytic Macrocytic
Iron deficiency Megaloblastic
• Fe ↓ • Hypersegmented neutrophils
• Ferritin ↓
• TIBC ↑ B12 deficiency
• Neurological problems
Thalassamia • Subacute combined degeneration of the cord
• Normal iron studies • Serum B12 ↓
• Electrophoresis to see type
Folate deficiency
Anaemia of chronic disease • Serum folate ↓
• Fe ↓
• Ferritin ↑
• TIBC ↓
Sideroblastic anaemia
• Fe ↑
• Ferritin ↑ Normoblastic (Non-megaloblastic
• In sideroblastic anaemia, the body has iron • Alcohol
available but cannot incorporate it into • Liver disease
haemoglobin • Hypothyroidism
• Pregnancy
• Reticulocytosis
• Myelodysplasia
• Drugs: cytotoxics
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Normocytic (normal MCV)
• Haemolytic anaemias: Bloods in general show ↑ LDH, ↑ unconjugated bilirubin,
↓haptoglobin, ↑ reticulocytes
Sickle cell
• Blood smear → Sickle cells
• Sickle solubility test → This test detects the presence of haemoglobin S but does not distinguish
between sickle cell disease and trait
• Hb electrophoresis → For asymptomatic patients to see if patient has trait
• Treatment: Acute → IV fluids, morphine, O2, antibiotics
• Prophylaxis → Hydroxyurea. Also needs pneumococcal vaccines
Autoimmune haemolysis
• COOMBS test
• Treat with steroids
Hereditary spherocytosis
• Blood film → spherocytes
• Osmotic fragility test
• Treatment: Splenectomy
G6PD deficiency
• Blood film → Heinz bodies
• Check G6PD levels
• Treatment: stop offending drugs
Q-5
A 41 year old man has fatigue and palpitations. Physical examination reveals a
red sore tongue, angular stomatitis and koilonychia. His blood tests show:
Haemoglobin 85 g/L
Mean cell volume 75 fL
A. Folate deficiency
B. Vitamin B12 deficiency
C. Iron deficiency
D. Vitamin E deficiency
E. Haemolytic anaemia
ANSWER:
Iron deficiency
EXPLANATION:
Angular stomatitis, sore red tongue can ben seen in both B12 deficiency andiron
deficiency although angular stomatitis is more of a sign of irondeficiency. Koilonychia is
usually seen in iron deficiency.
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But the key to the question is the mean cell volume. As this is decreased, itcannot be
B12 deficiency or folate deficiency. Iron deficiency leads tomicrocytic anaemia so we
would expect the MCV to be low.
Iron-deficiency anaemia
Aetiology
• Blood loss from the gastrointestinal (GI) tract is the most commoncause of iron-
deficiency anaemia in adult men and postmenopausalwomen
• Blood loss due to menorrhagia is the most common cause of irondeficiency in
premenopausal women
• In tropical countries, infestation of the gut may cause irondeficiencyanaemia ,
especially with hookworm and schistosomiasis
• Common causes of blood loss include:
• Non-steroidal anti-inflammatory drug (NSAID) use
• Colonic carcinoma
• Gastric carcinoma
• Gastric or duodenal ulceration
• Dietary inadequacy
• Failure of iron absorption: Malabsorption conditions such as coeliacdisease
• Excessive requirements for iron: Pregnancy
Laboratory tests
• Low Haemoglobin
• Low Mean cell volume (MCV)
• Low Mean cell haemoglobin concentration (MCHC)
• High Red cell distribution width (RDW)
• Low serum ferritin
• High Total iron-binding capacity
The above laboratory test are important to remember for PLAB as they maybe asked
Q-6
A 69 year old male presented to Accident & Emergency following a fall. He had
slippd and falledn in his home and his daughter had rushed him immediately to
A&E. His past medical history is significant for atrial fibrillation, which he takes
warfarin and atenolol for. He complains of a severe headache which he says is
getting worse. There is a small, tender bump on the right side of his head. His
Glasgow coma scale score is 15/15. A CT scan was done which shows a 1 cm by
2 cm right sided cerebral haematoma. Blood tests were also done and the results
are as follows:
Haemoglobin 158 g/L (130-180 g/L)

Platelets 253 x 109/L (150-400 x 109/L)
Prothrombin time (PT) 19 secs (10-14 secs)
Activated partial thromboplastin time (APTT) 39 secs (35-45 secs)
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International normalized ratio (INR) 3.3 (0.8-1.2)
Following the results of the CT scan and the results of the blood tests, he was
admitted and 5 mg of vitamin K1 was given intravenously. What is the SINGLE
next best treatment for this patient?
A. Intravenous mannitol
B. Intravenous prothrombin complex concentrate
C. Intravenous blood transfusion
D. Intravenous fresh frozen plasma
E. Intravenous prothrombin complex concentrate and fresh frozen plasma
ANSWER:
Intravenous prothrombin complex concentrate
EXPLANATION:
This patint has an INR (international normalised ratio) that is not within the therapeutic
range and he has a major bleed. For the purposes of the exam, a major bleed is an
intracranial or a gastrointestinal haemorrhage and a minor bleed is haematuria or
epistaxis.
If INR is higher than the target with a major bleed:

• Stop warfarin
• Give intravenous vitamin K 5 mg
• Prothrombin complex concentrate – if not available then give fresh frozen plasma
WARFARIN AND HIGH INR MANAGEMENT

NICE CKS has given clear guidance on actions required if the INR is above the target
range.
For major bleeding – stop warfarin, administer intravenous vitamin K1

(phytomenadione), administer prothrombin complex concentrate – if not available then
give fresh frozen plasma
For INR more than 8 with minor or no bleeding – stop warfarin, administer
intravenous or oral vitamin K1 (phytomenadione)
For INR between 6 and 8 with minor or no bleeding – stop warfarin, restart when
INR less than 5.
For INR between 5 and 6 but more than 0.5 units above the target range – reduce
the dose, or stop warfarin, restart when INR less than 5
For INR above target range but less than 5 – reduce or omit one or two doses and
measure INR in 2 to 3 days.
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Q-7
A 29 year old woman at 28 weeks gestation comes in for an antenatal visit. Her
blood tests reveal:
Hb: 11.0 g/dL

MCHC: normal range
MHC: normal
What is the SINGLE best explanation for these blood results?
A. Iron deficiency anaemia

B. Folate deficiency anaemia
C. Anaemia of chronic disease
D. Normal physiological phenomenon
E. Autoimmune anaemia
ANSWER:
Normal physiological phenomenon
EXPLANATION:
The British Committee for Standards in Haematology has defined anaemia
inpregnancy as the following values
Hb levels of:
<11.0g/dl in the first trimester
<10.5 g/dl in the second and third trimesters
<10.0 g/dl in the postpartum period.
Normal physiological changes in pregnancy
Haematological changes
• Plasma volume increases over the course of pregnancy by about50%. Dilutional
anaemia is caused by the rise in plasma volume.Elevated erythropoietin levels
increase the total red cell mass bythe end of the second trimester but haemoglobin
concentrationsnever reach pre-pregnancy levels.
• Usually mean corpuscular volume (MCV) and mean corpuscularhaemoglobin
concentration (MCHC) are unaffected.
• Serum iron falls during pregnancy whilst transferrin and total ironbinding capacity
rise.
Knowing the new British criteria for diagnosing anaemia in pregnancy isextremely
important for the PLAB 1 exam as is knowing the normalphysiological changes in
pregnancy. Many people get caught out with someof these physiological changes and
class them as pathological whereas infact, they are completely normal in pregnancy.
Q-8
A 67 year old man with history of weight loss complains of hoarseness of voice.
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Chest x-ray reveals opacity in the right upper mediastinum. He denies any
history of difficulty breathing. What is the SINGLE most appropriate
investigation?
A. Laryngoscopy
B. Bronchoscopy
C. Lymph node biopsy
D. Bronchoalveolar lavage
E. Barium swallow
ANSWER:
Lymph node biopsy
EXPLANATION:
Mediastinal masses are frequent and are sometimes discovered on a routine CXR in
lymphoma.
Tissue diagnosis is the best way to diagnose lymphoma. Lymph node excision biopsy
is what is usually done.
Q-9
A 21 year old man presents with mild jaundice.
Haemoglobin 75 g/L
Reticulocytes 7%
There are spherocytes seen on the blood film. He has no past medical history of
any significance. What is the SINGLE most appropriate investigation?
A. G6PD enzyme assay

B. Direct Coombs test
C. Indirect Coombs test
D. Bone marrow biopsy
E. Sickle solubility test
ANSWER:
Direct Coombs test
EXPLANATION:
The likely diagnosis here is the warm antibody induced haemolysis type of autoimmune
haemolytic anaemia. Most cases are idiopathic with no underlying pathology. The low
haemoglobin and high reticulocytes fit the picture. Mild jaundice and spherocytes can
also be seen.
Direct Coombs test is the investigation of choice.
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Autoimmune haemolytic anaemia
This occurs when RBCs react with autoantibody with or without a complement which
leads to premature destruction of RBCs by reticuloendothelial system.
Types of autoimmune haemolytic anaemia

• Warm antibody type:
• Idiopathic
• Secondary to other autoimmune diseases e.g. Systemic lupus erythematosus
(SLE)
• Secondary to lymphoproliferative diseases e.g. Lymphoma, Chronic lymphatic
leukaemia (CLL)
• Cold antibody type:
• Idiopathic
• Mycoplasma pneumoniae
• Infectious mononucleosis
Warm antibody induced haemolysis

• Most cases are idiopathic with no underlying pathology
• Affects predominantly individuals >50 years of age
• Clinical features
o Highly variable symptoms, asymptomatic or severely anaemic
o Mild jaundice
o Splenomegaly
• Diagnosis
o Anaemia
o Spherocytes on peripheral blood film
o Increased reticulocytes
o Detect on direct Coombs test
Cold haemagglutinin disease (CHAD)

• Describes syndrome associated with acrocyanosis in cold weather due to RBC
agglutinates in blood vessels of skin. Caused by RBC antibody that reacts most
strongly at temperatures below 32°C.
• May be idiopathic or secondary to infection with Mycoplasma or EBV (infectious
mononucleosis)
• Clinical features
o Acrocyanosis (blue discoloration of extremities e.g. fingers, toes) in cold conditions
o Splenomegaly
• Diagnosis
o Anaemia
o Increased reticulocytes
o Positive direct Coombs test
Q-10
A 47 year old man who is on warfarin therapy is due for a hemicolectomy. He is
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on warfarin for recurrent pulmonary embolism. What advice would you give him
prior to his surgery?
A. Continue with warfarin

B. Continue with warfarin and add heparin
C. Stop warfarin and start aspirin
D. Stop warfarin and start heparin
E. Stop warfarin
ANSWER:
Stop warfarin and start heparin
EXPLANATION:
Warfarin should always be stopped 5 days before planned surgery. Heparin is used
instead of warfarin prior to surgery in patients with intermediate to high risk of
thromboembolism, recent TIA or patients with mechanical cardiac valves.
Surgery and Warfarin

If the person needs to have surgery or any other invasive procedure, they may need to
temporarily stop taking warfarin.
Surgery — in general, warfarin is usually stopped 5 days before planned surgery, and
once the person's international normalized ratio (INR) is less than 1.5 surgery can go
ahead.
Warfarin is usually resumed at the normal dose on the evening of surgery or the next
day if haemostasis is adequate.
(In practice, you would need to adhere to local guidelines in Perioperative Bridging of
Warfarin in Adult Patients Undergoing Elective Surgery). See example of local
guidelines of guys and st thomas.)
Q-11
A 62 year old man presents with bone pain at his ribs and back pain which have
been present for the last couple of months. He has been feeling tired lately and
finds himself always thirsty. Blood tests were requested on his last visit which
show:
Haemoglobin 90 g/L
Calcium 4.0 mmol/L
Alkaline phosphatase (ALP) 118 U/L
Erythrocyte sedimentation rate (ESR) 88 mm/h
eGFR 45
What cell type is most likely to be found in abundance in the bone marrow?
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A. Plasma cell
B. Myeloid cell
C. Bence-Jones protein
D. Megakaryocytyes
E. Reticulocytes
ANSWER:
Plasma cell
EXPLANATION:
The clinical picture here is one of multiple myeloma. Multiple myeloma is a clonal
abnormality of plasma cells. Bone pain that is at the back and ribs are common
presentations. Hypercalcaemia and an elevated ESR are features of multiple myeloma.
Around 50% of patients with multiple myeloma would have renal impairment as seen in
this stem by having an eGFR of 45.
Bence-Jones is a protein not a cell.
MULTIPLE MYELOMA
A clonal abnormality of plasma cells resulting in their overproduction replacing the bone
marrow as well as the production of large quantities of functionless immunoglobulins.
• Bone disease
• Bone pain is the most common clinical manifestation.
• This is most commonly in the back and the ribs, secondary to pathologic fractures.
• Recurrent bacterial infection
• Due to abnormal immunoglobulin production which are functionally impaired
Remember, although there are large quantities of immunoglobulins, they do not
function well)
• Renal failure
• Anaemia → may present with weakness, fatigue, and pallor
• Hypercalcaemia → may present with polyuria, polydipsia, and altered mental status
Rarely, symptoms of a hyperviscosity syndrome such as blurry vision, and confusion,

may occur.
Diagnosis
• Although a normochromic, normocytic anaemia is the most common laboratory finding,
this is not specific for myeloma.
• A serum protein electrophoresis with a markedly elevated monoclonal immunoglobulin
spike is present in almost all cases
• Urine protein electrophoresis: looks for the presence of Bence Jones' protein.
• Plain x-ray of the skeletal system and skull will reveal the punched out lytic lesion
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caused by the overproduction of osteoclast activating factor from the plasma cells.
• Hypercalcaemia from the destruction of bone. Note that the hypercalcaemia is
associated with normal alkaline phosphatase.
• Elevation in the BUN and creatinine from the damage to the kidney from the
immunoglobulins
• A bone marrow biopsy with abundance of plasma cells confirms a diagnosis of multiple
myeloma
• Rouleaux formation can be seen on blood film (rouleaux means a cylindrical packet of
coins)
Management
This is beyond what will be asked in PLAB part 1
Q-12
A 39 year old woman presents with yellowing of her sclera and the complaint of
feeling tired all the time. She has no other complaints however, she mentions
that she had an upper respiratory tract infection a week ago. Her blood tests are
as follows:
Haemoglobin: 95 g/L
Bilirubin 28 micromol/L
Mean cell volume (MCV): 98 fL
Alanine transferase (ALT): 25 U/L
Aspartate transaminase (AST): 23 U/L
Alkaline phosphatase (ALP): 72 U/L
Gamma glutamyl transferase (GGT): 33 U/L
A peripheral blood smear is significant for polychromasia and scattered

spherocytes but no fragmented red blood cells or target cells were seen. What is
the SINGLE best diagnostic investigation?
A. Direct antiglobulin test

B. Indirect antiglobulin test
C. Osmotic fragility test
D. Bone marrow aspiration
E. Ultrasound of spleen
ANSWER:
Direct antiglobulin test
EXPLANATION:
This patient has a haemolytic anaemia. A direct antiglobulin test is a synonym for a
direct Coombs test.
The direct Coombs test is used to test for autoimmune haemolytic anaemia or in other
words any condition of an anaemia caused by immune system lysis or destruction of red
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blood cells.
Some examples of diseases that test positive for a direct Coombs test include
alloimmune haemolysis (such as Rhesus disease), autoimmune haemoloysis (such as
systemic lupus erythematosus) or drug-induced immune-mediated haemolysis.
The term “polychramasia” used in this stem refers to a disorder where there is an
abnormally high amount of immature red blood cells. A haemolytic anaemia such as
this case (or any other form of anaemia) would trigger erythropoeitin release and
increase the rate of which red blood cells are produced and released from the bone
marrow. When levels of erythropoeitin are high, immature red cells would be released
into the bloodstream.
COOMBS TEST
There are two Coombs tests:
1. The direct Coombs test (DCT, also known as direct antiglobulin test or DAT)
2. The indirect Coombs test (also known as indirect antiglobulin test or IAT)
Direct Coombs test

• Used to test for autoimmune haemolytic anaemia
• It is used to detect these antibodies or complement proteins that are bound to the
surface of red blood cells. Basically, it is used to test patients RED BLOOD
CELLS.
• A positive Coombs test indicates that an immune mechanism is attacking the
patient's
own RBCs. Examples:
• Common examples of alloimmune haemolysis
o Haemolytic disease of the newborn (also known as HDN or erythroblastosis
fetalis)
o Rh D haemolytic disease of the newborn (also known as Rh disease)
o ABO haemolytic disease of the newborn
o Alloimmune haemolytic transfusion reactions
• Common examples of autoimmune haemolysis
o Cold agglutinin disease : Infectious mononucleosis
• Drug-induced immune-mediated hemolysis
o Penicillins, Cephalosporins
Indirect Coombs test

• Used in prenatal testing of pregnant women and in testing blood prior to a blood
transfusion.
• It detects antibodies against RBCs that are present unbound in the patient's serum.
In this case, serum is extracted from the blood sample taken from the patient and
tested. Basically, it is used to test patients SERUM (not red blood
cells)
• If agglutination occurs, the indirect Coombs test is positive.
• Examples of use:
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o Blood transfusion preparation : Antibody screening, cross matching
o Antenatal antibody screening: to screen pregnant women for IgG antibodies
that are likely to pass through the placenta into the fetal blood and cause
haemolytic disease of the newborn
Direct Coombs test Indirect Coombs test

Tests a patient’s RED BLOOD CELLS Tests a patient’s SERUM
How the test works: How the test works

1. Blood sample is taken 1. Blood sample is taken
2. The RBCs are washed (patient’s plasma is 2. Serum is extracted from the blood sample
removed)
3. RBCs are incubated with anti-human globulin 3. Serum incubated with RBCs of known
(Coombs reagent) antigenicity, that is, RBCs with known reference
values from another patient’s blood sample.
4. If this produces agglutination of RBCs, the 4. Anti-human globulin is then added
direct Coombs test is positive.
5. A positive Coombs test indicates that an 5. If agglutination occurs, the indirect Coombs test
immune mechanism is attacking the patient’s is positive.
own RBCs
Q-13
A 6 year old boy is brought to the hospital by his mother with bleeding from his
gums and nose. His mother complains that he has been having recurrent sore
throats that come and go in last couple of months. Pale conjunctivae is noticed
on examination. What is the SINGLE most likely single cell type associated with
his diagnosis?
A. Clumped platelets
B. Microcytes
C. Granulocyte without blast cells
D. Blast cells
E. Mature lymphocytes
ANSWER:
Blast cells
EXPLANATION:
Before looking at the cell types, think of the diagnosis. The most likely diagnosis here is
Acute lymphoblastic leukaemia (ALL) as he is young, suffering recurrent infections (due
to abnormal WBCs), and having pale conjunctiva (anaemia). The bleeding gums and
nosebleeds tell you that he has thrombocytopaenia.
Acute lymphoblastic leukaemia (ALL) and acute myeloid leukaemia (AML) both have
numerous blast cells.
Aetiology
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Most cases of acute leukaemia arise with no apparent cause. There are several well
known associations with the development of acute leukaemia that are sometimes
present. These include radiation exposure, chemotherapeutic agents, as well as some
retroviruses.
The most common presentation results from the effects of the leukaemic blast cells
crowding out the normal marrow cells, resulting in symptoms of pancytopenia even if
the total white blood cell count is normal.
• Fatigue from anaemia is the most common presenting complaint.
• Bleeding, petechiae, purpura or ecchymoses (due to thrombocytopenia)
• Recurrent and severe infections (oral, throat, skin, perianal infections commonly). This
is because of the underproduction or abnormal function of white blood cells.
• Left upper quadrant fullness and early satiety due to splenomegaly (10-20%)
Acute lymphocytic leukaemia (ALL) is more common in children, and acute

myelogenous leukaemia (AML) is more common in adults, but they are indistinguishable
clinically. This means you cannot determine the diagnosis only from the clinical
presentation.
ALL is more often associated with infiltration of other organs, but AML can do it as well.
Enlargement of the liver, spleen, and lymph nodes and bone pain are common at
presentation.
Diagnosis
The FBC is the first clue to the diagnosis. Depression of all three cell lines is
common at presentation.
FBC
• Anaemia is usual and Hb may be below 5 g/L
• The white cell count can be low, normal, or elevated
• Thrombocytopenia
Many other disorders can present as pancytopenia similar to leukaemia such as aplastic
anaemia, infections involving the marrow, metastatic cancer involving the marrow,
vitamin B12 deficiency, SLE, hypersplenism, and myelofibrosis. However, none of these
will have leukaemic blasts circulating in the peripheral blood. Although pancytopenia
can cause all of the above, in PLAB, when pancytopenia is in the options, it is usually
leukaemia, or aplastic anaemia.
A bone marrow biopsy showing numerous blasts confirms the diagnosis of acute
leukaemia.
It is very unlikely that the PLAB questions would ask you to differentiate the AML from
ALL using specific test. However, if a child (young age) is given with signs and
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symptoms of pancytopenia, ALL would be the most likely as it is the commonest
Note:
• ALL is the commonest childhood leukaemia. Peak age is 2–4 years old.
• The Philadelphia chromosome occurs in 15–30% (mostly adults) and is associated
with a poor prognosis.
Q-14
A 55 year old man presents with “rubbery” painless lump on his neck. He also
has significant weight loss over the past 6 months, fever and night sweats. The
diagnosis of Hodgkin’s lymphoma was later confirmed with a lymph node
excision biopsy. What type of cell is associated with Hodgkin’s lymphoma?
A. T-cells
B. Reed-Sternberg cells
C. B-cells
D. Macrophages
E. Auer rods
ANSWER:
Reed-Sternberg cells
EXPLANATION:
A very easy and direct question. The diagnostic cells in Hodgkin’s lymphoma are Reed-
Sternberg cells.
HODGKIN'S LYMPHOMA
Hodgkin's lymphoma is a malignant tumour of the lymphatic system that is
characterised histologically by the presence of multinucleated giant cells (Reed-
Sternberg cells)
There are subtypes of Hodgkin's lymphoma but these are not commonly asked.
Presentation
• Enlarged but otherwise asymptomatic lymph node, typically in the lower neck or
supraclavicular region.
• The lymph nodes are described as painless, non-tender, and ‘rubbery’
• Mediastinal masses are sometimes discovered on a routine CXR.
• Systemic symptoms of drenching night sweats, unexplained fever >38°C, and weight
loss of >10% over six months are termed B symptoms and are identified in
approximately 25% of patients.
• Pruritus
• Lethargy
• Other findingsinclude splenomegaly (30%) and hepatomegaly (10%)
• Superior vena cava syndrome (SVC syndrome may occur due to ta compresion from
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mediastinal lymph node
Diagnosis
• Tissue diagnosis: Lymph node excision biopsy if possible
Q-15
A 90 year old woman is brought to the hospital complaining of back pain and has
been referred to the orthopaedic surgeon. She has been saying that her mother
is due to visit her today and that somebody must have broken her lower back as
she is in agony. Her blood tests show:
Haemoglobin 109 g/L

Serum urea 7.5 mmol/L
Serum creatinine 293 micromol/L
Serum calcium 3.02 mmol/L
What SINGLE investigations is most likely to lead to a diagnosis?
A. Ultrasound KUB
B. X-ray Spine
C. Intravenous urogram
D. Urine protein electrophoresis to look for Bence-Jones protein
E. Mental state exam
ANSWER:
Urine protein electrophoresis to look for Bence-Jones protein
EXPLANATION:
Multiple myeloma is the suspected diagnosis here and needs to be dealt with by the
haematologist.
Elevation in the BUN and creatinine is seen due to the damage to the kidney from the
immunoglobulins. Anaemia is the most common laboratory finding in multiple myeloma.
She is 90 years old. It is unlikely that her mother is still alive. The statement that she
thinks her mother is going to visit her today points to some sort of confusion. This
confusion can be seen in multiple myeloma due to hyperviscosity and also
hypercalcaemia.
Q-16
A 63 year old man presents with back pain, polydipsia and polyuria which have
been present for the last couple of weeks. He complains of being tired lately. He
has recurrent nose bleeds which started 6 months ago. His previous full blood
count shows a normocytic, normochromic anaemia. His eGFR was found to be
40. Monoclonal proteins were seen during further investigations of which he was
referred to secondary care. What is the SINGLE most appropriate investigation to
perform next that would lead to a diagnosis?
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A. Bone marrow biopsy
B. Vitamin D levels
C. Electrophoresis
D. Computed tomography scan of whole body
E. Renal biopsy
ANSWER:
Bone marrow biopsy
EXPLANATION:
The signs and symptoms together with the normochromic, normocytic anaemia are
indicative of multiple myeloma. Nosebleeds occur because the abnormal plasma cells
found in multiple myeloma inhibit the production of platelets.
Electrophoresis is already performed in this quesiton as monoclonal proteins can only

be seen during electrophoresis.
Once monoclonal proteins are found on electrophoresis, patients are usually referred to
haematology under the 2 week wait pathway. 2 week wait pathway means that you are
considering malignancy and the patient would be seen in secondary caere within 2
weeks. Secondary care would arrange a bone marrow biopsy, skeletal survey and 24
hour urine collection before constructing a plan. Amongst the options of investigations,
bone marrow biopsy would show an increased amount of plasma cells.
Q-17
A 32 year old woman has just had a laparoscopic cholecystectomy a few hours
ago. The nurse notices that she has a sore left leg with swollen varicose vein
extending from the mid-thigh to the ankle. She informs the nurse that she has
had that before surgery. She has no calf tenderness or calf swelling. What is the
SINGLE most appropriate action?
A. Prescribe nonsteroidal anti-inflammatory drugs (NSAIDs)
B. Prescribe antibiotics
C. Request for D-dimers
D. Request thrombophilia screen
E. Reassure
ANSWER:
Prescribe nonsteroidal anti-inflammatory drugs (NSAIDs)
EXPLANATION:
The condition that is described here is superficial thrombophlebitis. NSAIDs have been
shown to be effective in managing the pain for superficial thrombophlebitis.
Thrombophilia is not required for investigation of patients with superficial

thrombophlebitis.
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D-dimers would not be beneficial as it would usually be high after surgery. Furthermore,
it would be raised in both superficial thrombophlebitis and deep vein thrombosis.
SUPERFICIAL THROMBOPHLEBITIS
Superficial thrombophlebitis also known as superficial venous thrombosis occurs when
there is both thrombosis and inflammation of superficial veins most commonly affecting
the great saphenous vein of the legs.
The vast majority of superficial thrombophlebitis do not require antibiotics as they are
not infective. However, if there are signs of infection, flucloxacillin can be used.
Treatment for superficial thrombophlebitis evolves around

• Symptom reduction
• Prevention of deep venous thrombosis and pulmonary embolism
Symptom reduction
• Treatment of pain
o Oral or topical NSAIDs
o Paracetamol
• Management of swelling
o Compression stockings
o Leg elevation
Prevention of deep venous thrombosis and pulmonary embolism

• If has other risk factors for a DVT present, subcutaneous low molecular weight
heparin or fondaparinux can be used to prevent DVT
• If no other risk factors for DVT, low molecular weight heparin or fondaparinux not
required.
• If thrombosis is within 3 cm of the saphenofemoral junction, the British Haematology
Society guidelines recommend considering patients for treatment with low molecular
weight heparin or fondaparinux.
Are ultrasounds needed?

The short answer is yes!
• SIGN guidelines state that if there are clinical signs of superficial thrombophlebitis
affecting the proximal long saphenous vein, ultrasound scan is required to exclude
concurrent deep vein thrombosis.
• British Haematology Society guidelines state that patients with lower limb superficial
venous thrombosis should have ultrasound assessment to exclude deep venous
thrombosis, particularly if affecting the proximal long saphenous vein.
Are D-dimers required?

D-dimer is of little value as it cannot differentiate superficial from deep venous
thrombosis. It is seen elevated in both.
Q-18
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A 66 year old woman is confused, and lethargic. Her son reports gradual
confusion over the last 4 months. On examination, she looks pale. Blood tests
have been done which shows a megaloblastic anaemia. Both B12 deficiency and
folate deficiency was diagnosed on further investigation. What is the SINGLE
most likely treatment for her anaemia?
A. Oral folic acid and start intramuscular vitamin B12 when folic acid levels
are normal
B. Intramuscular vitamin B12 and start oral folic acid when vitamin B12 levels
are normal
C. Oral folic acid only
D. Intramuscular vitamin B12 only
E. Iron tablets
ANSWER:
Intramuscular vitamin B12 and start oral folic acid when vitamin B12 levels are normal.
EXPLANATION:
It is important in a patient who is deficient in both vitamin B12 and folic acid to treat the
B12 deficiency first to avoid precipitating subacute combined degeneration of the cord.
Once the vitamin B12 levels are normal, then start oral folic acid
FOLATE DEFICIENCY
Folate deficiency represents the other main deficiency cause of megaloblastic anaemia.
(The other main deficiency is B12 deficiency).
What are megaloblastic anaemias?

• A heterogeneous group of disorders sharing common morphological characteristics.
Erythrocytes are larger and have higher nuclear-to-cytoplasmic ratios compared to
normoblastic cells.
o Neutrophils can be hypersegmented
o Megakaryocytes are abnormal.
Causes:
Dietary deficiency
• Malabsorption (eg, coeliac disease, jejunal resection, inflammatory bowel disease).
• Poor intake
• Alcohol excess (also causes impaired utilisation)
Antifolate drugs
Example: Sulfasalazine, methotrexate
Diagnosis:
Haematological features for folate deficiency are indistinguishable from those of B12
deficiency (macrocytic, megaloblastic anaemia). Distinction is on basis of demonstration
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of reduced red cell and serum folate. Vitamin B12 levels should be assessed at the
same time due to the close relationship in metabolism.
In PLAB, one distinction that may help you choose between B12 and folate deficiency is
the diet. Good food sources of folate include broccoli, brussels sprouts, asparagus,
peas (basically vegetables). Thus if the given scenario is a vegetarian, it is unlikely that
he is suffering from folate deficiency. In that case, pick B12 deficiency.
Management:
Folic acid 5 mg/d PO for 4 months.
Note: It is important in a patient who is also deficient in both vitamin B12 and folic acid
to treat the B12 deficiency first to avoid precipitating subacute combined degeneration
of the cord. Once the vitamin B12 levels are normal, then start oral folic acid.
Q-19
A 10 year old girl presents with pallor and features of renal failure. She has
haematuria as well as proteinuria. The serum urea and creatinine are elevated.
These symptoms started after an episode of bloody diarrhoea 4 days ago. What
is the SINGLE most likely diagnosis?
A. Thrombotic thrombocytopaenic purpura

B. Haemolytic uraemic syndrome
C. Idiopathic thrombocytopaenic purpura
D. Henoch-Schonlein purpura
E. Acute renal failure
ANSWER:
Haemolytic uraemic syndrome
EXPLANATION:
Most cases of haemolytic uremic syndrome develop in children after 2 to 14 days of
diarrhoea often bloody, due to infection with a certain strain of E. coli. Common features
include abdominal pain, fever, features of renal failure like nausea/vomiting can also
occur.
Renal function and electrolytes would show a rise in urea and creatinine. This is due to
dehydration but, if associated with haemolysis and thrombocytopenia, then it would
indicate the onset of HUS.
A brief description:
Henoch-Schönlein purpura (HSP) Vs Haemolytic uraemic syndrome (HUS) Vs

Thrombotic thrombocytopenic purpura (TTP)
Henoch-Scholein Purpura Haemolytic Uraemic Syndrome Thrombotic Thrombocytopenic
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Purpura
- Purpura Triad Pentad (Triad of HUS)
- Abdomnial pain 1. Acute renal failure +
- Arthritis 2. Microangiopathic haemolytic 4. Neurological manifestation
- Glomerulonephritis anaemia (MAHA) 5. Fever
- Periarticular disease 3. Thrombocytopenia
- Periarticular oedema
Features of IgA nephropathy may

occur e.g. haematuria, renal
failure
Seen in Children Seen in Children

Usually follows an upper Associated with E. coli Inhibition of ADAMTS 13
respiratory tract infection • ADAMTS 13 is responsible
for breakdown of VWF –
Without ADAMTS 13,
coagulation occurs
Haemolytic uraemic syndrome (HUS)

HUS consists of a triad of haemolytic anaemia, uraemia, and thrombocytopenia.
The anaemia will be intravascular in nature and will have an abnormal blood smear
showing schistocytes, helmet cells, and fragmented red cells.
LDH and reticulocyte count will be elevated and the haptoglobin decreased.
90% are caused by E. coli strain O157. This produces a verotoxin that attacks
endothelial cells. Occurs after eating undercooked contaminated meat.
Signs and Symptoms:

The classical presenting feature is profuse diarrhoea that turns bloody 1 to 3 days later.
It is rare for the diarrhoea to have been bloody from the outset. About 80-90% of
children from whom the organism is isolated will develop blood in the stool. It is usually
at this stage that they are admitted to hospital.
Most adults infected with E. coli O157 remain asymptomatic.
There is often fever, abdominal pain and vomiting
Management
• Treatment is supportive e.g. Fluids, blood transfusion and dialysis if required
• Do not give antibiotics to those with possible HUS. The organism may release more
toxins as it dies if antibiotics are given and may worsen the disease.
• The indications for plasma exchange in HUS are complicated. As a general rule
plasma exchange is reserved for severe cases of HUS not associated with diarrhoea
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Q-20
A 65 year old man is brought by ambulance to the hospital for a suspected
stroke. The patient is on warfarin as part of his management for atrial fibrillation.
INR was ordered as part of a series of investigations and results have returned to
show an INR of 7.9. A computed tomography scan was performed and reveals an
intracranial haemorrhage. He currently has a blood pressure of 90/50 mmHg and
a heart rate of 120 beats per minute. As part of the management for the high INR
and bleeding, vitamin K was administered intravenously. What other products
can be given as part of the management for warfarin overdose?
A. Cryoprecipitate
B. Fresh frozen plasma
C. Red cell concentrate
D. Prothrombin complex concentrate
E. Tranexamic acid
ANSWER:
Prothrombin complex concentrate
EXPLANATION:
For major bleedings, these are the necessary steps:
• Stop warfarin
• Give intravenous vitamin K 5 mg
• Prothrombin complex concentrate – if not available then give fresh frozen plasma
Q-21
A 15 year old boy has marked pallor and jaundice. He has to receive regular
blood transfusions to maintain his haemoglobin above a certain level. His
medical history includes diabetes. He has obvious skull bossing and
hepatosplenomegaly. What is the SINGLE most likely diagnosis?
A. Hereditary spherocytosis
B. Glucose-6-phosphate dehydrogenase (G6PD) deficiency
C. Alpha thalassemia trait
D. Beta thalassemia major
E. Hereditary sideroblastic anaemia
ANSWER:
Beta thalassemia major
EXPLANATION:
The signs and symptoms point towards a beta thalassaemia major.
Alpha thalassemia trait have mild anaemia and are usually clinically asymptomatic
Thalassaemias
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Thalassaemia is not a very commonly asked topic. You should only go through this if
you have time to spare. We have only included the important points of thalassaemia.
Important points to know:

• α thalassaemia major → is usually lethal in utero. It should be considered when
hydrops fetalis is diagnosed
• β thalassaemia major → Presents in infancy often includes failure to thrive, vomiting
feeds, sleepiness, stunted growth and irritability. In severe, untreated cases there may
be:
• Hepatosplenomegaly
• Bony deformities (frontal bossing). The extra medullary haemopoiesis occurs in
response to anaemia.
• Marked pallor and slight to moderate jaundice
• Iron overload can cause endocrinopathy with diabetes, thyroid, adrenal and pituitary
disorders
• β-thalassaemia carrier status is often confused with iron deficiency due to reduced
MCV and MCH. But note that in iron deficiency, serum ferritin and iron is low while in
thalassaemia they are usually high.
Management for thalassaemia major:

• Lifelong blood transfusions are needed to maintain a haemoglobin level higher than
9.5 g/dL (or some authors say 9.0 g/dL)
• Iron chelation to prevent overload syndrome (Oral deferiprone + desferrioxamine SC
twice weekly)
• A histocompatible marrow transplant can offer the chance of a cure
Q-22
A 50 year old man presents fatigue, weight loss and complaints of abdominal
fullness. An abdominal examination reveals splenomegaly extending towards the
right iliac fossa.
Blood report shows the following:
Haemoglobin 82 g/L
White cell count 102 x 109/L
Philadelphia chromosome was positive on cytogenetic analysis. What is the

SINGLE most likely diagnosis?
A. Acute lymphoblastic leukaemia (ALL)

B. Acute myeloid leukaemia (AML)
C. Chronic myeloid leukaemia (CML)
D. Chronic lymphocytic leukaemia (CLL)
E. Lymphoma
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ANSWER:
Chronic myeloid leukaemia (CML)
EXPLANATION:
Anaemia, raised WBC count are known features of chronic myeloid leukaemia (CML).
Splenomegaly (particularly if massive) is very suggestive of chronic myeloid leukaemia
(CML) and Philadelphia chromosome is diagnostic of chronic myeloid leukaemia (CML).
Note that platelets can be normal in CML.

CML is a clonal bone marrow stem cell disorder in which a proliferation of mature
granulocytes (neutrophils, eosinophils and basophils) and their precursors is found.
CML typically progresses through three stages:

1. Chronic phase
The immune system is competent and patients are asymptomatic for prolonged periods
- (typically 4-5 years) More than 90% of patients are diagnosed in the initial chronic
phase.
2. Accelerated phase
In about two thirds of patients, the chronic phase transforms into an accelerated phase
characterised by a moderate increase in blast cells, increasing anaemia or
thrombocytopenia.
3. Blast crisis or blastic phase

After a variable amount of time (usually months) the accelerated phase progresses to
acute blastic transformation. Features of blastic phase include bone marrow or
peripheral blasts ≥30%, severe constitutional symptoms due to tumour burden (weight
loss, fever, night sweats, bone pain), infection and bleeding
Usually presents at age 40 to 50 years old (middle-age)
85-90% of patients are diagnosed in the chronic phase and in recent years
about 40% of patients have been diagnosed before any symptoms developed, with
incidental abnormalities spotted on a blood test.
• Fatigue (due to anaemia)

• Weight loss
• Night sweats
• Abdominal discomfort → from massive enlargement of spleen (this is common)
• Splenomegaly → this is the most common physical finding, which may extend towards
the right iliac fossa (Seen in >75%)
• Hepatomegaly
• Enlarged lymph nodes (rare)
• Low grade fever
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• Gout due to rapid cell turnover
Note: Enlarged lymph nodes are rare and infection are uncommon because these white
cells retain the majority of their function
Investigations at presentation
• FBC:
• Leukocytosis is common (often >100 x 109/L)
• Differential shows granulocytes at all stages of development (increased numbers of
neutrophils, myelocytes, basophils, eosinophils)
• Platelets may be elevated, decreased or normal levels
• A mild-to-moderate, usually normochromic and normocytic, anaemia is common
• Peripheral blood smear - all stages of maturation seen
• Biochemistry - U&Es are usually normal at presentation, lactate dehydrogenase is
usually raised, serum urate may be raised.
• Bone marrow aspiration and biopsy are essential to quantify the percentage of blasts
and basophils, to assess the degree of fibrosis and to obtain material for cytogenetic-
molecular analyses.
• Cytogenetics - the characteristic feature in CML is the Ph chromosome, found in about
90% of cases. (oxford says > 80%). This can be found on cytogenetic analysis of
blood or bone marrow.
Take home notes:

• The main feature of the disease is an elevated white blood cell count consisting
predominantly of neutrophils. Blasts are either absent or present in very small
amounts.
• The Philadelphia chromosome is present in more than 90% of patients with chronic
myeloid leukaemia (CML).
• In PLAB, look for the massive enlargement of spleen
Q-23
A 4 year old boy presents with haemrthrosis following a minor fall. His
grandfather and uncle have similar bleeding problems throughout their lives.
What is the SINGLE most likely mode of inheritance.
A. Autosomal co-dominant
B. Autosomal dominant
C. Autosomal recessive
D. X-linked
E. Mitochondrial gene defect
ANSWER:
X-linked
EXPLANATION:
Haemophilia A and B
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• Are congenital bleeding disorders with low levels of factor VIII (haemophilia A,
classical haemophilia) or IX (haemophilia B, Christmas disease).
• Sex-linked inheritance.
• Males are typically affected
• Female carriers are rarely symptomatic
Clinical presentation
• Haemophilia A and B are clinically indistinguishable
• Symptoms depend on the factor level.
• History of spontaneous bleeding into joints, especially the knees, ankles and elbows,
without a history of significant trauma. Spontaneous haemarthrosis are virtually
pathognomonic
• Intramuscular haemorrhage may also occur. Spontaneous bleeding into arms, legs, or
any site. The bleeding may lead to nerve compression, or compartment syndrome
Investigations
• Prothrombin time, bleeding time, fibrinogen levels and von Willebrand factor are
normal
• Activated partial thromboplastin time (APTT) is usually prolonged but can be normal in
mild disease
• Factor VIII/XI assay to diagnose
Remember these test to distinguish haemophilia from Von Willebrand disease

• Haemophilia
• Only aPTT is prolonged
• Has factor type bleeding (deep bleeding into muscles and joints)
• Von willebrand disease
• aPTT and bleeding time are prolonged
• Has platelet type bleeding (mucosal bleeding)
Haemophilia A-specific treatment

• Desmopressin raises factor VIII levels, and may be sufficient to treat Haemophilia type
A
• Major bleeds (eg haemarthrosis): May need treatment with recombinant factor VIII
• Do not give IM injections when factor is low
Haemophilia B-specific treatment

• Recombinant factor IX is the treatment of choice
• Note: Desmopressin has no value in treatment of haemophilia B
Avoid NSAIDS and IM injections!

Questions may arise with this topic. In PLAB, in whichever scenario, avoid NSAIDS and
IM injection as the answer in Haemophilia. NSAIDs must not be employed for the fear of
gastrointestinal haemorrhage. If needed, give opiates for pain relief and if given
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parenterally, pick intravenously (IV) or possibly subcutaneously (SC) but not
intramuscularly (IM). IM injection will produce a large and painful haematoma.
Q-24
A 42 year old woman with septicaemia suddenly develops purpura all over his
legs and arms. Her blood tests show:
Haemoglobin 118 g/L

Prothrombin time, and activated partial thromboplastin time are prolonged. D-

dimers were elevated. What is the SINGLE most likely diagnosis?
A. Pulmonary embolism
B. Disseminated intravascular coagulation
C. Deep vein thrombosis
D. Factor V Leiden mutation
E. Warfarin interaction
ANSWER:
Disseminated intravascular coagulation
EXPLANATION:
Disseminated intravascular coagulation (DIC)
Presentation
• Ecchymoses or spontaneous bleeding at venepuncture sites, and the site of trauma
• Bleeding from ears, nose and throat, gastrointestinal tract
• Petechiae, purpura
Diagnosis
No single laboratory test that can establish or rule out the diagnosis of DIC, therefore
assess the whole clinical picture, taking into account the clinical condition of the patient,
and all available laboratory results.
• Thrombocytopenia (in up to 98% of cases) → around 50% of them would have a

platelets count less than 50 x 109/L
• Fibrin degradation products (inc. D-dimer) is elevated
• Prothrombin time (PT) is elevated
• Activated partial thromboplastin time (aPTT) is elevated
• Fibrinogen level low
Remember, everything is elevated except platelets and fibrinogen.
Treatment
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• Treat the underlying condition
• Transfusion of platelets or plasma (components) for patients with severe bleeds
• In bleeding patients with DIC and prolonged PT and aPTT, administer fresh frozen
plasma (FFP)
Q-25
A 51 year old vegan presents with complaints of peripheral paresthesia, mild
shortness of breath and fatigue. Examination reveals that she has angular
stomatitis and a sore red tongue. What is the SINGLE most likely cell type to be
seen on a blood film?
A. Numerous blast cells

B. Oval macrocytic red cells
C. Spherocytes
D. Microcytic hypochromic red cells
E. Heinz bodies
ANSWER:
Oval macrocytic red cells
EXPLANATION:
Angular stomatitis is a known sign for iron deficiency anaemia however vitamin B12
deficiency is sometimes responsible for angular stomatitis, and commonly occurs
together with folate deficiency
The appearance of the tongue in vitamin B12 deficiency is described as "beefy" or "fiery
red and sore".
Peripheral paresthesia is also a known symptom of vitamin B12.
Vitamin B12 deficiency has RBC changes which include oval macrocytosis
Q-26
A 53 year old man presents complaining of weight loss, lethargy, increasing
abdominal discomfort and gout for the past year. On examination, spleen is
palpated 5 cm below the left costal margin. His blood tests show:
Haemoglobin 105 g/L

85% neutrophils
Sodium 140 mmol/L
Potassium 4 mmol/L
Philadelphia chromosome positive
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A. Chronic myeloid leukaemia

B. Chronic lymphocytic leukaemia
C. Acute myeloid leukaemia
D. Malaria
E. Lymphoma
ANSWER:
Chronic myeloid leukaemia
EXPLANATION:
The clincher here is the massive spleen. Although there are many causes of massive
spleen, for the purpose of PLAB, massive spleen can only be caused by chronic
myeloid leukaemia (CML) or Malaria
Weight loss, lethargy, increasing abdominal discomfort support the diagnosis of CML.
If you see a middle aged man/woman with a huge spleen → likely to be Chronic myeloid
leukaemia (CML). Malaria would likely have a travel history of some sort.
Mnemonic: CML → Crazy Massive Large Spleen
Q-27
A 75 year old man with chronic back pain and lethargy for several months was
referred to secondary care where further investigations were carried out.
Amongst the investigations was a bone marrow biopsy which was reported as
having abundance of plasma cells. What is the SINGLE most likely diganosis?
A. Multiple myeloma
B. Ankylosing spondylitis
C. Amyloidosis
D. Leukaemia
E. Myelofibrosis
ANSWER:
Multiple myeloma
EXPLANATION:
A bone marrow biopsy with abundance of plasma cells is diagnostic for multiple
myeloma.
Q-28
A 38 year old female presents with the complaint of worsening tiredness. She
says that she first began to notice her increasing fatigability two weeks ago. On
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examination, she appeaers to be mildly jaundiced. No other significant signs
appear on physical examination. Her heart rate is 79 beats/minute and her blood
pressure is 120/70 mmHg. Baseline bloods were taken and the results are as
follows:
Haemoglobin 92 g/L
Mean cell volume (MCV) 98 fL
White cell count (WCC) 8 x 109/L
Alanine transferase (ALT) 21 U/L
Aspartate transaminase (AST) 27 U/L
Alkaline phosphatase (ALP) 140 U/L
Gamma glutamyl transferase (GGT) 39 U/L
What is the SINGLE most appropriate diagnostic investigation for this patient?
A. Bone marrow aspiration

B. Direct antiglobin test
C. Faecal occult blood test
D. Serum antinuclear antibodies
E. Vitamin B12 levels
ANSWER:
Direct antiglobin test
EXPLANATION:
All the indications point toward this patient having a haemolytic anaemia.
A direct antiglobin test is a synonym for a direct Coombs test which would be
appropriate to test for autoimmune haemolytic anaemia.
Haemolysis causes an increase in the serum bilirubin levels, which is present in this
patient’s blood results.
The only blood values that are not within the normal range for this patient are her
haemoglobin levels, her MCV value and her bilirubin levels. Everything else is within
the normal range.
What about the increased MCV?

While it is true that most cases of an increased mean cell volume can be seen in the
macrocytic anaemias notably B12 deficiency and folate deficiency which are, by
definition, not haemolytic anaemias, some immunologically-mediated haemolytic
anaemias may be seen to have spherocytes on microscopy and have an increased
MCV. These immunologically-mediated haemolytic anaemias would have a positive
direct Coombs test.
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Q-29
A 21 year old man has episodic right upper quadrant pain. An abdominal
ultrasound reveals gallstones. His father had a splenectomy when he was young.
His blood tests show:
Haemoglobin 91 g/L
Mean cell haemoglobin concentration 369 g/L
B. Glucose-6-dehydrogenase (G6PD) deficiency
C. Alpha thalassemia
D. Beta thalassemia
ANSWER:
Hereditary spherocytosis
EXPLANATION:
The evidence of increased MCHC, gallstones and family history points towards
hereditary spherocytosis.
Hereditary Spherocytosis
Hereditary Spherocytosis is the most common inherited RBC membrane defect
characterized by variable degrees of haemolysis, spherocytic RBCs with increased
osmotic fragility.
Approximately 75% of cases display an autosomal dominant pattern of inheritance; the

rest are recessive forms and de novo mutations.
Clinical features
• Patients may present at any age with haemolytic anaemia, jaundice (either from
haemolysis or gallstones) and splenomegaly
• 20-30% of patients have mild disease with an increased red cell turnover
compensated with adequate replacement. They are neither symptomatic nor anaemic,
but may have mild splenomegaly, slight reticulocytosis and minimal spherocytes
visible.
• 60-70% of patients have moderate disease and half of these present in childhood with
anaemia.
• Neonates with severe hereditary disease do not always present at birth with anaemia,
but haemoglobin may fall dramatically over the first few weeks of life and may be
severe enough to require exchange transfusion.
• Occasional aplastic crises occur, e.g. with parvovirus B19 infection.
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Diagnosis
(These are the 3 most important test that you need to know in the exam for Hereditary
Spherocytosis)
• Blood film shows spherocytes and increased reticulocytes
• MCHC would be elevated
• Osmotic fragility test → confirms presence of spherocytes but does not permit
hereditary spherocytosis to be distinguished from other spherocytic haemolytic
disorders such as autoimmune haemolytic anaemia. This is not reliable until six
months of age.
Some authors mention that osmotic fragility test is unreliable and is no longer
recommended. However, it is still considered the gold standard despite missing up to
20% of cases. In the PLAB exam, osmotic fragility test may be given as a choice for a
diagnostic test for Hereditary Spherocytosis. Pick it if it is.
Note:
Spherocytosis almost always refers to hereditary spherocytosis but note that
spherocytes are found in hereditary spherocytosis and also autoimmune haemolytic
anaemias. The test to distinguish the two would be a direct Coombs test. Hereditary
spherocytosis has a negative direct Coombs test but autoimmune haemolytic anaemias
have a positive direct Coombs test
Management
Steroid therapy
• effective in augmenting haemoglobin levels during haemolytic crises in patients with
moderate disease
Folate supplementation
Splenectomy
• eliminates anaemia and hyperbilirubinaemia and lowers the high reticulocyte number
to nearly normal levels
• Splenectomy is curative in most patients but increased recognition of the long-term
risks of splenectomy has led to re-evaluation of the role of splenectomy.
Mild cases do not usually require folate supplements or splenectomy
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Complications
• Rapid haemolysis can be triggered by viral infections and produce jaundice, anaemia
and occasionally abdominal pain and tender splenomegaly. Supportive treatment is
usually all that is needed.
• Aplastic crises (aplastic anaemia). They are most commonly caused by infection with
parvovirus B19 and usually last 10-14 days. This can be life-threatening.
When you see parvovirus B19 in the exam, immediately think of sickle cell anaemia or
hereditary spherocytosis
Parvovirus and anaemia

Although most patients have a decrease of erythropoiesis (production of red blood cells)
during parvovirus infection, it is most dangerous in patients with sickle cell anaemia or
hereditary spherocytosis, as they are heavily dependent on erythropoiesis due to the
reduced lifespan of the red cells.
Q-30
A 45 year old man presents fatigue. He is otherwise asymptomatic. Blood report
shows the following:
Haemoglobin 82 g/L
There was an increased number of neutrophils, basophils, eosinophils.

Peripheral blood smear shows all stages of maturation. What is the SINGLE most
likely diagnosis?

E. Lymphoma
ANSWER:
Chronic myeloid leukaemia
EXPLANATION:
Anaemia, raised WBC count are known features of chronic myeloid leukaemia (CML).
Myeloid cells include neutrophils, basophils, eosinophils, erythrocytes, and platelets. An

increased number of neutrophils, basophils, eosinophils are consistent with CML.
Note that platelets can be low, normal or raised in CML.
Q-31
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A 10 year old boy is brought to the hospital with a rash over his buttocks
associated with abdominal pain and vomiting. He is accompanied by his mother
and stepfather. His mother had left him for the weekend with the stepfather and
she was called to come back from holiday as he started to have blood in his urine
with the rash. Social services have been notified. What is the most likely
diagnosis?
A. Non accidental injury

B. Idiopathic thrombocytopenic purpura
C. Henoch Schonlein purpura
D. Acute lymphoblastic leukaemia (ALL)
E. Haemolytic uraemic syndrome
ANSWER:
Henoch-Schonlein purpura
EXPLANATION:
Rash over buttock, abdominal pain and vomiting, blood in urine or stool suggest
Henoch-Schönlein purpura.
A mixed picture question like this can be sometimes confusing as in this question there
are some features of a non accidental injury (stepfather). Be sure to evaluate all the
signs and symptoms before jumping to the conclusion that this is a non accidental
injury.
Henoch-Schönlein purpura (HSP)

Presentation:
• Purpura (non-blanching) over buttocks and extensor surfaces
• Arthralgia (especially in the knees and ankles)
• Abdominal pain
Diagnosis:
• Mainly a clinical diagnosis
• Look for elevated ESR, IgA
• Raised creatinine ; labs consistent with nephropathy
Treatment:
• Self-limiting; conservative management
• NSAIDs for arthralgic pain → beware of choosing this option if case stem has impaired
renal involvement!
• Corticosteroids can improve associated arthralgia and the symptoms associated with
gastrointestinal dysfunction
Q-32
A 7 year old boy has recurrent episodes of spontaneous bleeding into his knee
joints and muscles. Factor IX was found deficient. What is the SINGLE most
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likely diagnosis?
A. Haemophilia A
B. Christmas disease
C. Von Willebrand’s disease
D. Sickle cell anaemia
E. Thalassaemia
ANSWER:
Christmas disease
EXPLANATION:
Factor Ix deficiency is evidence of haemophilia B (Christmas disease)
Q-33
A 22 year old Greek man presents with rapid symptoms of anaemia and jaundice
following treatment of malaria. He is noted to have Heinz bodies on a blood film.
A. Glucose-6-phosphate dehydrogenase (G6PD) deficiency

B. Anaemia of chronic disease
C. Pernicious anaemia
D. Thalassaemia trait
ANSWER:
Glucose-6-phosphate dehydrogenase (G6PD) deficiency
EXPLANATION:
Heinz bodies are pathognomic for G6PD deficiency. In PLAB, if you see a question that
has Heinz bodies on a blood film, you can almost be certain that this is G6PD
deficiency.
Haemolysis in this case was elicited by treatment of malaria. Usually primaquine is the
culprit.

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is X-linked and clinically
important cause of oxidant haemolysis. It affects all races but is most common in those
of African, Asian or Mediterranean descent.
Deficiency of the G6PD enzyme results in reduced glutathione making the red cells
vulnerable to oxidative damage and thus liable to haemolysis.
↓ G6PD enzyme → ↓ glutathione → ↑ red cell susceptibility to oxidative stress
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• Being X-linked, the disease affects mainly men but in areas of high frequency it is
not uncommon to find homozygous women. (In the exam, it is usually always male
patient)
• Most individuals with the G6PD defect are asymptomatic and unaware of their
status
• Haemolysis occurs after exposure to oxidants or infection.
• Acute episodes of haemolysis with fava beans (termed favism)
There are many drugs that can elicit haemolysis in patients with G6PD deficiency. One
drug that you would definitely need to look out for in the exam is → antimalarials:
primaquine
Presentation:
• Most are asymptomatic
• May be a history of neonatal jaundice, severe enough to require exchange transfusion
• May have history of drug-induced haemolysis
• Gallstones are common
• Pallor from anaemia
• During a crisis jaundice occurs
• Back or abdominal pain (usually occurs when >50% haemolysis occurs)
• Splenomegaly may occur
There are typically 4 ways the patient might present in PLAB. Below are the
specifics:
Drug-induced haemolysis in G6PD deficiency

• Begins 1-3 days after ingestion of drug
• Anaemia most severe 7-10 days after ingestion
• Associated with low back and abdominal pain
• Urine becomes dark (black sometimes)
• Red cells develop Heinz body inclusions
• Haemolysis is typically self-limiting
Haemolysis due to infection and fever

• 1-2 days after onset of fever
• Mild anaemia develops
• Commonly seen in pneumonic illnesses
Favism
• Hours/days after ingestion of fava beans (broad beans)
• Urine becomes red or very dark
• Shock may develop and it may be fatal
Neonatal jaundice
• May develop kernicterus (possible permanent brain damage)
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Laboratory investigation (Important for exam)
• In steady state (i.e. no haemolysis) the RBCs appear normal
• Heinz bodies is seen on blood film in drug-induced haemolysis. Bite cells are also
seen. Bite cells are cells with Heinz bodies that pass through the spleen and have part
of the membrane removed
Laboratory investigations (Less important for exam)

• Spherocytes and RBC fragments on blood film is seen if there is
severe haemolysis
• Increased reticulocytes
• Increased unconjugated bilirubin
• decreased haptoglobins
Diagnosis
G6PD enzyme activity - is the definitive test
Diagnosis should not be done during the haemolytic episode but be done during the
steady state which is around 6 weeks after the episode of haemolysis. The reason
behind this is the diagnosis is difficult during haemolytic episode since reticulocytes
have increased levels of enzyme and may get abnormal result.
Management
• Avoidance of precipitating drugs, and broad (fava) beans
• Transfuse in severe haemolysis or symptomatic anaemia
• IV fluids to maintain good urine output
• In infants, exchange transfusion may be required
• Splenectomy may be of value in severe recurrent haemolysis
Q-34
A 49 year old lady complains of headaches, dizziness and pruritus. She says that
the pruritus is worsened after taking a hot bath. A recent FBC revealed that she
has a haemoglobin of 192 g/L. What is the SINGLE most useful test to establish
the diagnosis of polycythaemia rubra vera?
A. JAK mutation screen

B. Leukocyte alkaline phosphatase
C. Serum erythropoeitin
D. Oxygen saturation with arterial blood gas greater than 92%
E. Bone marrow aspiration
ANSWER:
JAK mutation screen
EXPLANATION:
It has recently been established that a mutation in JAK2 is present in approximately
95% of patients with PRV. JAK2 mutation is now a major criteria in the diagnosis of
polycythaemia rubra vera.
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Polycythaemia rubra vera (PRV)
Polycythaemia rubra vera (PRV) is the most common form of primary polycythaemia. It
is a malignant proliferation of a clone derived from one pluripotent marrow stem cell.
• There is excess proliferation of RBCs, WBCs, and platelets, leading to hyperviscosity
and thrombosis
• More commonly found in patients who are more than 60 years old
• A mutation in JAK2 is present in >90%
Presentation
• It may be discovered on routine blood count in a person with no related symptoms or
there may be nonspecific complaints of lethargy and tiredness
• About a third present with symptoms due to thrombosis. Features include stroke,
myocardial infarction, deep vein thrombosis and pulmonary embolism
• Headaches, dizziness, sweating, and tinnitus
• Bleeding from gums or easy bruising is usually mild but gastrointestinal haemorrhage
can be more severe. This is secondary to abnormal platelet function
• Pruritus which is typically worse after a hot shower or bath
• Splenomegaly is present in about 75% of patients (oxford says 60%)
• Hypertension is common
• Erythema, warmth, pain, and even sometimes infarction of the distal extremities.
Burning sensation in fingers and toes, are characteristic but not very common
• Facial plethora
• Gout from increased cell turnover
Note:
• There is usually an abnormally low serum erythropoietin
Management
• Venesection
• Chemotherapy options include:
• Younger than 40 years of age: first-line is interferon
• Older than 40 years of age: first-line is hydroxycarbamide (hydroxyurea)
• Low dose aspirin 75mg OD → To reduce thrombotic events
Q-35
A 32 year old man presents with fatigue, weakness, weight loss. On examination,
cervical lymphadenopathy and splenomegaly is noted. What is the SINGLE most
likely diagnosis?
A. Haemophilus influenzae infection

B. Streptococcal infection
C. Toxoplasmosis
D. Non-Hodgkin lymphoma
E. Pneumocystis infection
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ANSWER:
Non-Hodgkin lymphoma
EXPLANATION:
There are two major points mentioned here: cervical lymphadenopathy and
splenomegaly.
This combination makes Non-Hodgkin lymphoma as the most likely cause.
Toxoplasmosis although uncommon, may have cervical lymphadenopathy and

splenomegaly as well. But weight loss is not seen in toxoplasmosis hence non-
hodgkin's lymphoma remains the top choice.
This includes all lymphomas without Reed-Sternberg cells
Most are derived from B-cell lines; diffuse large B-cell lymphoma (DLBCL) is
commonest.
Common Signs and Symptoms

• Painless, slowly progressive peripheral lymphadenopathy is the most common
clinical presentation
• Primary extranodal involvement and systemic symptoms (fatigue, weakness, fever,
night sweats, weight loss) are not common at presentation but are common in
patients with advanced or endstage disease.
Note: fever, night sweats, weight loss are less common than in Hodgkin’s
lymphoma, and indicates disseminated disease
• Bone marrow is frequently involved and may be associated with pancytopenia -
anaemia, infection, bleeding (platelets).
• Splenomegaly
• Hepatomegaly
Q-36
A 20 year old man presents with development of low back pain, shortness of
breath and dizziness 3 days after taking primaquine to treat malaria. His past
medical history is significant for neonatal jaundice. What is the SINGLE most
likely diagnosis?
A. Haemolytic anaemia
B. Pulmonary embolism
C. Allergy to primaquine
D. Thalassaemia trait
ANSWER:
Haemolytic anaemia
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EXPLANATION:
Haemolysis in this case was elicited by the treatment of malaria using primaquine. This
patient has G6PD deficiency.
Q-37
A 51 year old man complains of headache and pruritus. He had a deep vein
thrombosis recently. Recent blood reports show the following:
Haemoglobin 192 g/L

Erythropoietin was found to be low. What is the SINGLE most likely diagnosis?
A. Myelofibrosis
B. Polycythaemia rubra vera (PRV)
C. Essential thrombocythemia
D. Chronic myeloid leukaemia (CML)
E. Chronic lymphocytic leukaemia (CLL)
ANSWER:
EXPLANATION:
The signs and symptoms are consistent with polycythaemia rubra vera (PRV)
About a third of patients with PRV present with symptoms due to thrombosis. This
includes DVT like in this question.
PCV is usually associated with a low serum level of the hormone erythropoietin (EPO).
Q-38
A 17 year old girl has prolonged bleeding after a routine dental extraction. Her
father and paternal grandomother have experienced similar problems. What is
the SINGLE most likely mode of inheritance?
A. Autosomal co-dominant
B. Autosomal dominant
C. Autosomal recessive
D. X-linked
E. Mitochondrial gene defect
ANSWER:
Autosomal dominant
EXPLANATION:
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Although type 3 von Willebrand disease is actually autosomal recessive, majority of von
Willebrand’s disease is autosomal dominant.
Von Willebrand disease

The 3 important points you need to know in Von Willebrand disease in PLAB is:
1. It presents with mucosal bleeding → Epistaxis, menorrhagia (behaves like a platelet
disorder)
2. AAutosomal dominant (type 3 is recessive)
3. Role of Von Willebrand's factor is:
a. Promotes platelet aggregation
b. Carrier molecule for factor VIII
Investigation
• Bleeding time → prolonged
• APTT → prolonged
• Factor VIII levels may be moderately reduced
• Defective platelet aggregation with ristocetin
Management
• Tranexamic acid for mild bleeding
• Desmopressin (DDAVP): raises levels of vWF by inducing release of vWF
• Factor VIII concentrate
Comparing the 3 important bleeding disorders in PLAB
Von Willebrand disease Haemophilia Disseminated

intravascular coagulation
(DIC)
Platelet type bleeding Factor type bleeding (deep Bleeding everywhere
(mucosal bleeding) bleeding into muscles and • Venepuncture sites
joints) • GI tract
• Ear nose throat
• Skin: Purpura
aPTT prolonged aPTT is prolonged aPTT prolonged
Bleeding time prolonged Bleeding time prolonged
PT prolonged
Q-39
A 5 year old boy has swelling at the knee after falling on the ground with rashes
on his buttocks. His blood tests show:
Haemoglobin 119 g/L
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Prothrombin time 12 seconds
Activated partial thromboplastin time 61 seconds
A. Haemolytic uraemic syndrome

B. Haemophilia
C. Henoch-Schonlein purpura
D. Osler Weber Rendu syndrome
E. Von Willebrand disease
ANSWER:
Haemophilia
EXPLANATION:
As a general rule, platelet deficiency causes petechial haemorrhages and ecchymoses
(bruising) whilst clotting factor deficiency produces haematomas and haemarthroses.
This question gives a mixed picture where there are descriptions of both platelet
deficiency (petechial haemorrhages seen on his buttocks) and factor deficiency
(bleeding/swelling at his knee). However, the prolonged aPTT supports the diagnosis of
haemophilia thus that is the answer. We can only hope that in PLAB, these mixed
picture questions are low in number for you exam.
Q-40
A 4 year old boy presents with fever, and decreased appetite. On examination,
there are palpable non-tender nodules along the deep cervical chain in the neck.
He has a history of recurrent throat infections. His mother describes him as
always feeling tired. On examination, splenomegaly was noted. Blood results
show:
Haemoglobin 9 g/dL
MCV 80 fl
A. Acute myeloid leukaemia

B. Acute lymphoblastic leukaemia
C. Chronic myeloid leukaemia
D. Chronic lymphocytic leukaemia
ANSWER:
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EXPLANATION:
This is a frequent topic on PLAB 1. Be sure to know the differentiations between all the
leukaemias and be able to classify them by the age groups. Acute lymphoblastic
leukaemia (ALL) is the most common paediatric cancer. The differentiating factor
between ALL and acute myeloid leukaemia (AML) is AML would present with massive
splenomegaly on examination. ALL would just have lymphadenopathy.
But in actual fact, AML and ALL are usually indistinguishable clinically. This means you
cannot determine the diagnosis only from the clinical presentation. ALL is more often
associated with infiltration of other organs, but AML can do it as well. Acute lymphocytic
leukaemia (ALL) is more common in children, and acute myelogenous leukaemia (AML)
is more common in adults
It is very unlikely that the PLAB questions would ask you to differentiate the AML from
ALL using specific test. However, if a child (young age) is given with signs and
symptoms of pancytopenia, ALL would be the most likely as it is the commonest
Q-41
A 72 year old man with a background of vascular dementia living alone has been
brought in by his daughter to the Emergency Department for the third time this
month for bruising around the head, face and forearms. His son in law has been
stayingwith him recently as the patient has not been able to manage alone. He is
on warfarin for atrial fibrillation and is otherwise not taking any other
medications. His blood results done in the department show the following:
Haemoglobin 82 g/L
International normalized ratio (INR) 1.1
What is the SINGLE most likely cause for these symptoms?
A. Non-accidental injury
B. Accidental falls
C. Heparin induced thrombocytopaenia
D. Increased prothrombin time
E. Side effect of warfarin
ANSWER:
Non-accidental injury
EXPLANATION:
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This elderly man is probably quite aggressive and difficult to manage. The presence of
bruising on the forearms is reflective of him trying to defend himself and push someone
away. The facial bruising is suspicious of abuse.
Option B. Accidental falls is incorrect. Most injuries in these cases involve hip joints or
shoulder joints. There is no mention of hip or shoulder pains in this case.
Option C. Heparin induced thrombocytopaenia is incorrect. There is no history of use

of heparin
Option D. Increased prothrombin time is incorrect. This disturbance of coagulation

does not cause bruising but can make it so that bruising can persist for longer than
normal.
Option E. Side effect of warfarin is incorrect. His INR is within normal limits.
Furthermore, one would expect more generalised bruising over the entire body as
opposed to the face and head.
Q-42
A11 year old boy has an upper respiratory tract infection followed by a low grade
fever with erythematous macular rash, especially on the back of the legs. A few
hours later, the macules evolve into purpuric lesions that are slightly raised and
do not blanch on a glass test. He also complains of a headache and joint
stiffness. His blood tests show:
Haemoglobin 123 g/L

A. Meningitis
B. Sepsis
D. Idiopathic thrombocytopenic purpura
E. Thrombotic thrombocytopenic purpura
ANSWER:
EXPLANATION:
The blood results are all normal. The rash in the legs that are non blanching and the
arthritis are hints towards Henoch-Schönlein purpura.
The disease occurs mostly in the winter months. About 50-90% of patients have a
preceding upper respiratory tract infection (URTI) which explains the cough in the given
question.
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The stem here gives a no history of fever. Generally, patients with Henoch-Schönlein
purpura appear to be mildly ill, with low-grade fever. But having no fever does not
exclude the diagnosis.
Q-43
A 26 year old man develops mild anaemia following a chest infection. A blood
film shows Heinz bodies. What is the SINGLE most likely diagnosis?
C. Alpha thalassaemia
D. Beta thalassaemia
ANSWER:
EXPLANATION:
Heinz bodies are pathognomic for G6PD deficiency. In PLAB, if you see a question that
has Heinz bodies on a blood film, you can almost be certain that this is G6PD
deficiency.
Q-44
A 5 year old child has bleeding gums and sore throat for the last 3 months. He
feels tired and lethargic all the time. On examination, splenomegaly was noted.
Blood results show:
Hb 7.8 g/dL
WCC 3 x 109/L

ANSWER:
EXPLANATION:
The commonest leukaemia in children is Acute lymphoblastic leukaemia (ALL)
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Bleeding gums (low platelet), feeling tired and lethargic, sore throat, splenomegaly are
all well known features of Acute lymphoblastic leukaemia (ALL)
Q-45
A 29 year old man has back pain and abdominal pain following treatment of
malaria. His urine has become dark and his eyes have a yellowish tinge. He has
had gallstones in the past. His past medical history includes jaundice when he
was a neonate. What is the SINGLE most likely diagnosis?
A. Glucose-6-phosphate dehydrogenase (G6PD) deficiency

B. Allergy to antimalaria medication
C. Steven-John syndrome
D. Peptic ulcer disease
E. Beta thalassaemia
ANSWER:
EXPLANATION:
Haemolysis in G6PD deficiency patients can be elicited by treatment of malaria. Back
pain and abdominal pain can be seen in severe haemolysis occurring in G6PD
deficiency.
History of gallstones and neonatal jaundice support the diagnosis of G6PD deficiency.
Q-46
A 7 year old boy presents with epistaxis of 2 hour duration. The bleeding has
been controlled. His blood tests show:

Bleeding time is normal
A. Haemophilia
B. Von Willebrand disease
C. Idiopathic thrombocytopenic purpura
D. Vitamin K deficiency
E. Anatomical defect
ANSWER:
Anatomical defect
EXPLANATION:
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All his blood results are normal. Anatomical defect is the only possiblity.
Q-47
A 16 year old boy presents with a palpable rash on his buttocks and extensor
surface of his arms and legs following a sore throat. He complains of joint
stiffness, joint pains and crampy abdominal pain. On urine testing, microscopic
haematuria and proteinuria are found. What is the SINGLE most probable
diagnosis?
A. Measles
B. Thrombotic thrombocytopenic purpura (TTP)
C. Meningococcal septicaemia
D. Idiopathic thrombocytopenic purpura (ITP)
E. Henoch-Schonlein purpura (HSP)
ANSWER:
Henoch-Schonlein purpura (HSP)
EXPLANATION:
The purpuric rash found in HSP is typically over buttocks and extensor surfaces of arms
and legs. Arthrlagia occurs in 80% of patients and gastrointestinal symptoms like
abdominal pain occur in around 30% of patients. Renal involvement is usually seen in
the older children which can be identified by microscopic haematuria or proteinuria.
Q-48
A 22 year old man is admitted to the hospital with lethargy. His medical history
includes hereditary spherocytosis. His blood tests show:
Haemoglobin 51 g/L
Reticulocytes 0.4%
What is the SINGLE most likely cause of his low haemoglobin and low
leukocytes?
A. Parvovirus B19 infection

B. Autoimmune haemolytic anaemia
C. Splenic sequestration crisis
D. Haemolytic transfusion reactions
E. Recent antibiotic treatment
ANSWER:
Parvovirus B19 infection
EXPLANATION:
Parvovirus B19 infection can cause an aplastic crises in patients with hereditary
spherocytosis. This can be life-threatening and often requires blood transfusion.
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Splenic sequestration crisis is a wrong answer. A patient with a sequestration crisis is
also severely anaemic , but the reticulocyte count will be high, in contrast to the aplastic
crisis where the reticulocyte count is low or zero. Splenic sequestration crisis is also
usually seen in sickle cell.
Q-49
A 55 year old man complains of fatigue. A blood test shows:
Haemoglobin 82 g/L
What is the most likely diagnosis?
B. Thalassaemia major
C. Iron deficiency anaemia
E. Sickle cell anaemia
ANSWER:
Folate deficiency
EXPLANATION:
The best option above is folate deficiency as it is a macrocytic anaemia (high MCV)
Q-50
A 45 year old man presents with a lump in the posterior triangle of his neck. It
has been growing for the past few months. He also complains of having
drenching night sweats, unexplained fever and weight loss. Lymph nodes are
palpable at the supraclavicular region. What is the SINGLE most likely
diagnosis?
A. Tuberculosis
B. Lymphoma
C. Lipoma
D. Reactive lymph nodes
E. Virchow’s nodes
ANSWER:
Lymphoma
EXPLANATION:
This is quite the classical presentation of lymphoma.
• Drenching night sweats, fever, weight loss
• Enlarged but otherwise asymptomatic lymph node, typically in the lower neck or
supraclavicular region
• Occasionally, findings on examination may reveal hepatomegaly or splenomegaly.
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In this question thankfully you do not need to differentiate between Hodgkin’s and non-
Hodgkin’s.
Q-51
A 51year old man complains of lethary, tiredness and pruritus. The pruritus is
worse after he takes a hot shower. He also says that he feels a burning sensation
in his fingers and toes. Splenomegaly was found during an abdominal
examination. His medical history is significant for gout. What is the SINGLE
most likely diagnosis?
A. Polycythaemia rubra vera (PRV)

B. Myelofibrosis
C. Rheumatoid arthritis
D. Scleroderma
E. Systemic lupus erythematosus
ANSWER:
EXPLANATION:
The signs and symptoms are consistent with polycythaemia rubra vera (PRV).
Gout can be seen in PRV. This is due to an increased cell turnover.
Q-52
A 51 year old male presents with malaise and tiredness. On physical exam, his
spleen is noted to be approaching his right iliac fossa. No lymphadenopathy was
noticed. What is the SINGLE most likely cell type to be seen on a blood smear?
A. Helmet shaped cell

B. Sickle cell
C. Granulocyte without blast cells
D. Blast cells
E. Target red cells
ANSWER:
Granulocyte without blast cells.
EXPLANATION:
The clincher here is the massive spleen that approaches the right iliac fossa. Although
there are many causes of massive spleen, for the purpose of PLAB, massive spleen
can only be caused by chronic myeloid leukaemia (CML) or malaria.
If you see a middle aged man/woman with a huge spleen → likely to be Chronic myeloid
leukaemia (CML). Malaria would likely have a travel history of some sort.
Mnemonic: CML → Crazy Massive Large Spleen
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Q-53
A 50 year old woman is investigated for anaemia. She has no past medical
history of note. Clinical examination reveals massive splenomegaly associated
with pale conjunctivae. A full blood count was requested and results show:
Haemoglobin 105 g/L

A. Chronic lymphocytic leukaemia

C. Myeloma
E. Malaria
ANSWER:
Chronic myeloid leukaemia.
EXPLANATION:
Please see Q-53
Q-54
A 7 year old boy has recurrent epidoses of spontaneous bleeding into his knee
and elbow joints. Mild joint deformity is noted. Factor VIII/IX assay shows a
decrease in factor VIII. What is the SINGLE most appropriate management?
A. Desmopressin
B. Recombinant factor IX
C. Heparin
D. Infusion of platelet concentrates
E. Vitamin K
ANSWER:
Desmopressin
EXPLANATION:
Factor VIII deficiency is evidence of haemophilia A. Desmopressin is one of the
treatment choices.
Q-55
A 28 year old man has sudden onset of bone pain. He also begins experiencing
bleeding from his gums. Looking retrospectively, he notes a decreased energy
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level over past weeks. He feels dizzy and has dyspnoea on exertion. He looks
pale and has numerous ecchymoses seen over his body. Hepatosplenomegaly is
noted. A full blood count shows WBC of 102 x 109/L. A bone marrow biopsy
shows numerous blasts. What is the SINGLE most likely diagnosis?
A. Mantle cell lymphoma

B. Infectious lymphocytosis
C. Waldenstrom’s macroglobulinemia
D. Acute myeloid leukaemia (AML)
E. Acute lymphoblastic leukaemia (ALL)
ANSWER:
Acute myeloid leukaemia (AML)
EXPLANATION:
This is actually an acute emergency. The leucocytosis is causing the bone pain.
Bleeding from the gum is commonly seen in acute myeloid leukaemia
(AML).
Note that gum bleeding can also be seen in ALL.
AML is the most common acute leukaemia in adults. Thus, majority of the acute
leukaemia in children questions asked in the PLAB test would be acute lymphoblastic
leukaemia (ALL) and not acute myeloid leukaemia (AML).
One needs to be careful with picking AML or ALL as there are often questions with a
very similar stem. In reality, it is difficult to diagnose them clinically as well. Flow
cytometry (immunophenotyping) is used to help distinguish AML from acute lymphocytic
leukemia (ALL).
Acute myeloid leukaemia (AML)

This neoplastic proliferation of blast cells is derived from marrow myeloid elements. It
progresses rapidly (death in about 2 months if untreated)
Children or young adults may present with acute symptoms over a few days to a few
weeks.
Most AML subtypes show more than 30% blasts of a myeloid lineage in the
blood, bone marrow, or both.
Presentation:
• Fatigue, pallor, dizziness and shortness of breath on exertion (symptoms of anaemia)
• Bleeding caused by thrombocytopenia. Thrombocytopenia often causes petechiae on
the lower limbs. DIC may aggravate the situation and cause larger lesions
• Infection
• Gingivitis is common, with swollen, bleeding gums
• There can also be bone pain
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• Hepatomegaly and splenomegaly may be found. Lymphadenopathy is less common.
Investigations
• FBC:
• Total WBC count is often high. However, it may also be normal or even low
• Neutrophils are usually depleted and blast cells are seen in their place
• Bone marrow aspiration is the diagnostic procedure. (The WHO classification requires
more than 20% blasts in the peripheral blood, to make a diagnosis of AML)
Q-56
A 34 year old woman developed a purpuric rash on the back of her legs. She also
reports frequent nose bleeds and menorrhagia. A blood count shows:
Haemoglobin 119 g/L

A. Idiopathic thrombocytopenic purpura

B. Thrombotic thrombocytopenic purpura
C. Von Willebrand’s diease
D. Antiphospholipid syndrome
E. Henoch-Schonlein purpura
ANSWER:
Idiopathic thrombocytopenic purpura
EXPLANATION:
Idiopathic thrombocytopenic purpura is usually seen in children but that does not mean
it can’t happen in adults.
Chronic ITP which is mainly seen in women can run a fluctuating course of bleeding,
purpura, epistaxis and menorrhagia.
The isolated thrombocytopenia in a well patient points to a diagnosis of idiopathic

thrombocytopenic purpura.
Idiopathic thrombocytopenic purpura in adults

Unlike ITP in children, adult ITP does not normally follow an infection and usually has
an insidious onset. It is more likely to follow a chronic course in affected adults than in
children.
Presentation:
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• As in children, adults with ITP may demonstrate a range of symptoms from none at all
through to severe haemorrhage
• Bleeding, purpura, epistaxis and menorrhagia
Laboratory diagnosis
• Isolated thrombocytopenia; blood count otherwise normal
Management:
• Prednisolone
• IV immunoglobulin
• Emergency platelet transfusion
• Only in life threatening haemorrhage. (usually platelet less than 20 x 109/L)
Q-57
A 26 year old Greek man has recently recovered from a haemolytic episode 6
weeks ago. The haemolytic episode occurred a day after he ate a traditional
Greek dish. Glucose-6-phosphate dehydrogenase deficiency is suspected. What
is the SINGLE most definitive diagnostic test?
A. Osmotic fragility test

B. G6PD enzyme assay
C. Heinz bodies seen on blood film
D. Bite cells seen on blood film
E. Decreased haptoglobins and increased reticulocytes
ANSWER:
G6PD enzyme assay
EXPLANATION:
G6PD enzyme activity is the definitive test
Osmotic fragility test is to diagnose Hereditary spherocytosis. Heinz bodies and bite
cells seen on blood film are important investigations that point towards G6PD but are
not the definitive diagnostic test.
Q-58
A 67 year old woman with a history of rheumatoid arthritis presents to her GP’s
office with complaints of epigastric discomfort, especially after eating. She has
been on long term methotrexate and NSAID therapy for her condition. On
examination, she appears pale but seems otherwise well. A full blood count
reveals the following:
Haemoglobin 105 g/L

MCV, MCH and MCHC are seen to be decreased
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A. Folate deficiency anaemia
B. Vitamin B12 deficiency anaemia
C. Haemolytic anaemia
D. Aplastic anaemia
E. Chronic gastrointestinal bleeding
ANSWER:
Chronic gastrointestinal bleeding
EXPLANATION:
The blood values are indicative of a microcytic anaemia. It is true that methotrexate can
cause a folic acid deficiency anaemia but since the blood results clearly show a
microcytic anaemia (and folic acid deficiency anaemia is a macrocytic anaemia) the only
correct conclusion that we can reach is that the long term NSAID therapy si the culprit
for her anaemia.
Q-59
A 20 year old woman has had bruising and petechiae for a week. She also
reports frequent nose bleeds and menorrhagia but is otherwise well. A blood
count showed:
Haemoglobin 111 g/L

A. Acute leukaemia
B. Aplastic anaemia
C. HIV infection
E. Systemic lupus erythematosus
ANSWER:
EXPLANATION:
Idiopathic thrombocytopenic purpura is usually seen in children but that does not mean
it can’t happen in adults.
As the patient is otherwise well, acute leukaemia, HIV and SLE are unlikely. A normal
WBC count excludes aplastic anaemia. Thus the likely diagnosis is ITP. Idiopathic
thrombocytopenic purpura fits with her symptoms of bruising and petechiae. Older girls
may have menorrhagia. Some experience nosebleeds.
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The isolated thrombocytopenia in a well patient points to a diagnosis of
idiopathic thrombocytopenic purpura.
Q-60
A 54 year old woman is diagnosed with deep vein thrombosis after taking a long
haul flight. She is started on warfarin. What is the target INR for her?
A. <1
B. 1-2
C. 2-3
D. 3-4
E. 2-5
ANSWER:
2-3
EXPLANATION:
INR is derived from the PT ratio and is a standardized method of reporting which
permits comparability between laboratories.
The INR range of 2 to 3 is appropriate for:

• Prophylaxis or treatment of venous thromboembolism
• Reduction of the risk of systemic embolism for people with atrial fibrillation and valvular
heart disease
For the purpose of PLAB, just remember that INR of 2 to 3 is the answer for majority of
cases. The only cases where a higher INR is required, is in the cases of a mechanical
heart valve replacement. Patients with metallic valves require lifelong anticoagulation
with a target INR of 3 to 4.
Q-61
A 65 year old man presents with back pain. Abdominal examination shows
splenomegaly
Blood report shows the following:
Haemoglobin 102 g/L

ESR 25
He has been found to have Philadelphia chromosome on cytogenetic analysis.


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E. Lymphoma
ANSWER:
EXPLANATION:
Anaemia, raised WBC count, low platelet (platelet may be variable) are known features
of Chronic myeloid leukaemia (CML)
Splenomegaly (particularly if massive) is very suggestive of Chronic myeloid leukaemia

(CML) and Philadelphia chromosome is diagnostic of Chronic myeloid leukaemia
(CML).
Q-62
A 55 year old HIV man presents with painless peripheral lymphadenopathy, fever,
night sweats and weight loss. Abdominal examination reveals an enlarged
spleen. What is the SINGLE most likely diagnosis?
A. Hodgkin’s lymphoma
B. Non-Hodgkin’s lymphoma
C. Acute lymphoblastic leukaemia (ALL)
D. Acute myeloid leukaemia (AML)
E. Chronic myeloid leukaemia (CML)
ANSWER:
Non-Hodgkin’s lymphoma
EXPLANATION:
Although both Hodgkin’s and Non-Hodgkin’s lymphoma present in similar ways with
lymphadenopathy, night sweats, fever, weight loss, non-Hodgkin’s is more associated
with HIV than hodgkin’s disease. Non-Hodgkin's lymphoma (NHL) is known as AIDS-
related lymphoma.
The most prevalent of the HIV-related lymphomas is diffuse large B-cell non-Hodgkin's
lymphoma, followed by Burkitt's lymphoma.
Although not considered an AIDS-defining illness, Hodgkin's lymphoma is increasing in

incidence in those with HIV infection and would be considered an answer to this
question if NHL was not present as one of the answers.
There is a clear correlation between the degree of immunosuppression and the risk of
developing NHL. The pathogenesis is rather the immunosuppression rather than the
HIV itself.
Q-63
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A 45 year old woman who is taking medication for the treatment of rheumatoid
arthritis presents with dizziness, fatigability and lack of energy. Blood results
show:
Haemoglobin 80 g/L
What is the SINGLE most likely cause of her anaemia?
A. Steroids
B. Chronic disease
C. NSAIDs
D. Methotrexate
E. Leflunomide
ANSWER:
Methotrexate
EXPLANATION:
Methotrexate is a folate antagonist. It causes folate deficiency which is shown as a
macrocytic anaemia like in the case above.
Anaemia of chronic disease would be considered as a cause if the MCV was normal or
low. Rheumatoid arthritis leading to anaemia of chronic disease has red cells that are
usually hypochromic, microcytic or normochromic, normocytic.
Q-64
A 30 year old woman presents with complaints of lethargy and frequent
infections. On examination, her spleen is not palpable and there are no
associated lymphadenopathy. A full blood count reveals the following:
Haemoglobin 85 g/L
What tissue biopsy will you do to prove the diagnosis?
A. Liver
B. Lymph node
C. Spleen
D. Bone marrow
E. Lung
ANSWER:
Bone marrow
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EXPLANATION:
According to her lab results, this woman appears to have a pancytopenia (reduction in
all three haematopoietic cell lines). In order to prove a diagnosis of aplastic anaemia, a
bone marrow biopsy must be done.
Please note that pancytopenia and aplastic anaemia are NOT interchangeable
terms.
• Pancytopenia is a decrease in all three haematopoietic cell lines. Pancytopenia can
be suspected from a full blood count with or without a peripheral blood smear.
• Aplastic anaemia is pancytopenia AND histological evidence of a hypoplastic bone
marrow. It is a diagnosis of exclusion and can only be made by a bone marrow
biopsy.
Q-65
A 25 year old lady has a chest infection which she is receiving antibiotics for.
She has shortness of breath, feels tired and weak. On examination, she looks
pale and purpura is seen on her legs. Blood results show the following:
Haemoglobin 76 g/L
Neutrophils 0.3 x 109/L
Plaletets 19 x 109/L
Reticulocytes 1%
Blood film morphology was unremarkable. A bone marrow aspirate shows a

reduction in haemopoietic cells. What is the SINGLE most likely underlying
diagnosis?
A. Pernicious anaemia
C. Aplastic anaemia
E. Acute lymphoblastic leukaemia
ANSWER:
Aplastic anaemia
EXPLANATION:
She has signs and symptoms of anaemia. The blood picture shows pancytopenia which
rules out pernicious anaemia as an underlying cause.
Normal morphology rules out the possibility of acute myeloid leukaemia, and acute
lymphoblastic leukaemia.
Chronic myeloid leukaemia usually has leucocytosis.
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A bone marrow aspirate that shows a gross reduction in all haemopoietic tissue is seen
classically in aplastic anaemia. Decrease reticulocytes support the diagnosis.
Q-66
A 30 year old woman complains of tiredness, lethargy and constipation. On
inspection, she has dry coarse skin, hair loss and cold peripheries. On
examination, a diffuse and lobulated goitre can be palpated on her anterior neck.
A full blood count and peripheral smear is done which shows a macrocytic
anaemia. What is the SINGLE most likely diagnosis?
A. Cushing’s syndrome
B. Hyperthyroidism
C. Crohn’s disease
D. Addison’s disease
E. Pernicious anaemia
ANSWER:
Pernicious anaemia
EXPLANATION:
This is a multi-part question. Her symptoms are indicative of hypothyroidism. Her signs
are indicative of Hashimoto’s Thyroiditis (an autoimmune thyroid disorder). Since
Hashimoto’s is an autoimmune disease and her blood smear shows a macrocytic
anaemia, a logical conclusion would be that she is suffering from pernicious anaemia
(also an autoimmune disease).
Some points to remember for the PLAB 1 exam:
Growth patterns of goitres

• Iodine deficiency (rare in the developed world): diffuse
• Hashimoto’s Thyroiditis: diffuse and lobulated
• Pituitary disease: diffuse
• Grave’s Disease: diffuse
• Thyroid cancer and benign thyroid growths: uninodular
If you have difficulty remembering this long list just remember: all goitres grow diffuse
except Hashimoto’s (diffuse AND lobulated) and benign/malignant thyroid growths
(uninodular).
Associations of hypothyroidism
• Obstructive sleep apnoea
• Carpal tunnel syndrome
• Galactorrhoea/hyperprolactinaemia
Q-67
A 20 year old man with sickle cell anaemia has shortness of breath, pallor,
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headache and lethargy. He has been having flu-like symptoms for the past week.
For the past few days, he has been having aches on his hands, knees and ankles.
His initial blood tests show:
Haemoglobin 53 g/L
Infection with parvovirus B19 is suspected and further blood tests have been sent
for specific IgM and IgG antibodies to parvovirus B19. What is the SINGLE most
likely diagnosis?
A. Aplastic crises
B. Haemolytic crises
C. Splenic sequestration crisis
D. Vaso-occlusive crises
E. Acute chest syndrome
ANSWER:
Aplastic crises
EXPLANATION:
When you see parvovirus B19 in the exam, immediately think of sickle cell anaemia or
hereditary spherocytosis with the diagnosis of aplastic crisis at hand.
Parvovirus is also a risk factor for splenic sequestration crisis however infection with
parvovirus B19 is more commonly associated with aplastic crisis in patients with sickle
cell anaemia.
In adults, parvovirus B19 can present with flu-like symptoms and symmetrical joint pain
and stiffness involving joints of the hands, knees, wrists and ankles. This usually
resolves in weeks.
Another group of people that you should be worried about parvovirus infections are
pregnant women as they can affect the fetal red blood cells causing aplastic anaemia.
The anaemia can be particularly severe due to the short life span of fetal erythrocytes.
Sickle cell crisis

Sickle cell anaemia is characterised by periods of good health with intervening crises
There are four main types of crises:
Thrombotic crises (Vaso-occlusive crises)

• Most common type of crisis
• Caused by obstruction of the microcirculation by sickled red blood cells, causing
ischaemia
• Precipitated by cold, infection, or dehydration – Some patients would know their
triggers and develop strategies to avoid them however majority of painful episodes
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have no identifiable cause.
• Occlusion causes pain which may be severe
• Infarcts occur in various organs
Commonly presenting scenarios in exams are
• Occlusion causing mesenteric ischaemia, mimicking an acute abdomen
• Avascular necrosis e.g. femoral head
Sequestration crises
• Is the sudden enlargement of the spleen, causing a decrease in haemoglobin
concentration, circulatory collapse and hypovolaemic shock
• Occurs mainly in babies and young children
• Occurs mainly in babies and young children
• Reticulocyte count would be increased
• Recurrent splenic sequestration is an indication for splenectomy
Aplastic crises
• Characterized by a rapid drop in haemoglobin level caused by a transient cessation of
erythropoiesis (production of red blood cells)
• Leads to a rapid reduction in red cell precursors in the bone marrow and a markedly
reduced number of reticulocytes in the peripheral blood
• Caused by an infection with parvovirus B19
Most patients have a decrease of erythropoiesis (production of red blood cells) during
parvovirus infection, however it is most dangerous in patients with sickle cell anaemia or
hereditary spherocytosis, as they are heavily dependent on erythropoiesis due to the
reduced lifespan of the red cells.
Haemolytic crises
• Rare thus uncommon to be asked in PLAB
• During painful crises there may be a marked increase in the rate of haemolysis with a
fall in the haemoglobin level
Q-68
A 48 year old woman hasbecome increasingly fatigued over the past 10 months.
Vitiligo of the hand was noted. Her blood tests show:
Haemoglobin 88 g/L
B. Thalassaemia minor
C. Pernicious anaemia
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E. Sickle cell anaemia
ANSWER:
Pernicious anaemia
EXPLANATION:
The mean cell volume is increased. This points towards either a B12 deficiency or
folate deficiency
Pernicious anaemia is one of the causes of a B12 deficiency and it may coexist with
other autoimmune disease such as vitiligo. Note that hypothyroidism is also another
coexisting autoimmune disease to look out for.
Q-69
A 4 year old boy presents with recurrent episodes of self limiting spontaneous
bleeding into his arms and legs that occurs with minimal trauma. His blood tests
show:

Bleeding time is normal
What is the SINGLE most likely diagnosis
A. Haemophilia
B. Thalassaemia
ANSWER:
Haemophilia
EXPLANATION:
Activated partial thromboplastin time (APTT) that is prolonged with everything else
being normal points towards haemophilia.
Factor VIII and IX levels should be offered to confirm the diagnosis.
Q-70
A 12 year old boy has sudden development of purpura 2 weeks after an upper
respiratory tract infection. A blood count showed:
Haemoglobin 119 g/L

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Bleeding time 10 minutes
A. Idiopathic thrombocytopenic purpura

B. Thrombotic thrombocytopenic purpura
D. Haemophilia A
E. Haemophilia B
ANSWER:
EXPLANATION:
The isolated thrombocytopenia and history of an upper respiratory tract infection with
the development of purpura suggest idiopathic thrombocytopenic purpura.
In idiopathic thrombocytopenic purpura, bleeding time may be increased like the above.

Presentation:
• Follows viral infection or immunisation
• The most common presentation is petechiae or bruising. Petechiae mainly in arms and
legs - sudden onset
• Up to a quarter present with nosebleeds
• Haematuria and gastrointestinal bleeds are less common.
• Older girls may have menorrhagia
• Otherwise the patient is well and physical examination is normal
Laboratory diagnosis
• Isolated thrombocytopenia; blood count otherwise normal
Management:
• Prednisolone
• IV immunoglobulin
• Emergency platelet transfusion
• Only in life threatening haemorrhage. (usually platelet less than 20 x 109/L)
Q-71
A 75 year old male presents with enlarged cervical nodes. He has several
recurrrent infections over the year. His conjunctiva is pale and he feels weak.
What is the SINGLE most likely cell type to be found on a blood smear of this
patient?
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A. Granulocytes without blast cells
B. Myofibroblasts
C. Plasma cells
D. Mature lymphocytes
E. Sickling of cells
ANSWER:
Mature lymphocytes
EXPLANATION:
The diagnosis here is Chronic lymphocytic leukaemia (CLL) which has mature
lymphocytes on the blood film.
Factors that support the diagnosis of CLL in this question:

• His age (75 years old) - In the PLAB test, if you see an elderly patient (usually more
than 65 years old) with symptoms of leukaemia, it is most likely CLL. However, read
the whole question before you make a decision on the answer.
• Cervical lymphadenopathy
• Recurrent infections → dysfunctional WBC
• Pale conjunctiva → Anaemia
On blood film, B cell lymphocytosis will be seen often with smudge cells. They are
mature but functionally impaired lymphocytes as they escape apoptosis.
Chronic lymphocytic leukaemia (CLL)

CLL can often present as an asymptomatic elevation of white cells found on routine
evaluation of patients during investigations for other health problems. These patients
are exclusively older (majority over 50 years old).
When patients do have signs and symptoms they are usually non-specific:
• Fatigue
• Lethargy
• Enlargement of lymph nodes
When should you suspect CLL?

When an older patient has marked elevation in white cell count with marked lymphocytic
predominance. The marrow is often infiltrated with leukemic lymphocytes. “Smudge
cells” are seen on smear.
Q-72
A 6 year old child has a history of recurrent mild jaundice that occurs a few days
after the onset of a fever. Between the episodes he is well. 3 days ago, he had a
chest infection and his blood results show:
Haemoglobin 106 g/L

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Bite cells are seen on blood film. What is the SINGLE most likely diagnosis?
C. Thalassaemia
D. Sickle cell disease
E. Congenital storage disorder
ANSWER:
EXPLANATION:
There are some precipitating factors of haemolysis causing jaundice in patients with
G6PD deficiency. Among then include infection. Bite cells point towards the diagnosis
of G6PD.
Q-73
A 13 year old boy presents complains of pins and needles sensation in his feet.
He does not suffer from any medical conditions and takes no regular medication.
He denies any palpitations, shortness of breath or lightheadedness. On
examination, his tongue appears to be swollen and inflamed. He has a BMI of 15
kg/m2. His FBC shows the following:
Haemoglobin of 80 g/L
A smear shows oval macrocytes and hypersegmented neutrophils. The patient

mentions that he has recently become vegan and in the morning, only has time
for a cup of tea before heading off to school. What is the SINGLE best treatment
for this patient?
A. Packed red cell blood transfusion

B. Parenteral iron
C. Pyridoxine
D. Vitamin C
E. Hycroxycobalamin and folic acid
ANSWER:
Hydroxycobalamin and folic acid
EXPLANATION:
This patient has a vitamin B12 deficiency due to low intake.
Vegan diet patients such in the above stem is already a huge hint towards vitamin B12
deficiency. The fact that he has a low BMI is a hint that he has an improper diet.
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The signs and symptoms are nonspecific – you cannot clinically differentiate between
B12 deficiency anaemia and folic acid deficiency but for PLAB remember that patients
with B12 deficiency often present with some form of neurological disturbance
(peripheral neuropathy in this stem)
As there is no option for hydroxycobalamin alone, pick the one with the combination of
hydroxycobalamin and folic acid.
Blood transfusion should NOT be considered if the patient has no symptoms of anaemia
where the Hb is 80 g/L or more.
Usually, blood transfusions are considered if there are:

• Symptoms of anaemia and haemoglobin is less than 80 g/L
• Haemoglobin less than 70 g/L in an asymptomatic patient
Q-74
A 34 year old male patient with estbalished Burkitt’s lymphoma is undergoing
chemotherapy. He is currently at week two of treatment. He complains of only
passing very little amounts of urine in the past 24 hours and feeling more
lethargic than usual. Upon routine blood testing, he was found to have the
following lab values:
Potassium 5.9 mmol/L

Urea 18 mmol/L
Creatinine 289 micromol/L
Serum calcium (total) 1.9 mmol/L
What SINGLE most appropriate investigation will you perform to aid in

management of this patient?
A. Serum urate
B. Serum alkaline phosphatase
C. C-reactive protein (CRP)
D. 24 hour urinary calcium
E. Serum parathyroid hormone
ANSWER:
Serum urate
EXPLANATION:
This patient is suffering from tumour lysis syndrome. Tumour lysis syndrome is a
severe metabolic disturbance following the rapid lysis of malignant cells a short while
after chemotherapy, radiotherapy, surgery or ablation procedures. It is an oncological
emergency. It occurs most often in patients with acute lymphoblastic leukaemia (ALL)
or Burkitt’s lymphoma. In this stem, Burkitt’s lymphoma was present.
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Tumour lysis syndrome would result in the following blood results
• Hyperuricaemia
• Hyperkalaemia
• Hyperphosphataemia
• Hypocalcaemia
Although a full biochemical profile is needed to diagnose tumour lysis syndrome uric
acid levels would help confirm the diagnosis of tumour lysis syndrome
TUMOUR LYSIS SYNDROME

Important key featuresto remember for tumour lysis syndrome
• History of Leukaemia or Burkitt’s lymphoma
• Chemotherapy
• Acute renal failure
• Hyperuricaemia, hyperkalaemia, hyperphosphataemia, hypocalcaemia
• IV fluids as part of management
Tumour lysis syndrome involves a rapid tumour cell lysis leading to large amounts of
potassium, phosphate and uric acid released into the bloodstream. In the exam, it
usually follows a patient with malignancies who has recently been treated with
chemotherapy.
It is considered a hematology and oncology emergency as it is life threatening and has

associated renal, cardiac and neurological complications.
Seen in highly chemosensitive neoplasms such as leukaemia and non-Hodgkin’s

lymphoma (particularly Burkitt’s lymphoma).
The following metabolic abnormalities develop rapidly

• Hyperuricaemia
o Due to massive cell death and nuclear breakdown generating large amounts of
nucleic acids of which the purines are converted into uric acid
o Causes gout due to monosodium urate crystals and renal colic due to formation
of renal stones
• Hyperkalaemia
o Due to rapid cell lysis
o Often the earliest sign of tumour lysis syndrome
o Causes paraesthesia, muscle weakness and arrhythmias
• Hyperphosphataemia
o Due to rapid cell lysis
o Causes acute kidney failure due to deposition of calcium phosphate crystals in
renal parenchyma
• Hypercalcaemia
o Secondary to hyperphosphataemia (phosphates bind to calcium forming calcium
phosphate crystals)
o Causes tetany
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Acute renal failure occurs due to uric acid nephropathy, acute nephrocalcinosis and
precipitation of xanthine.
Treatment
Rehydration with intravenous fluids
Management is complicated but for the exam, all that is required is the knowledge that
this patient requires intravenous fluids
Q-75
A 15 year old boy is investigated after he bled excessively following a tooth
extraction. He has always noted that he bruises easily with minimal trauma. His
blood tests show:
Haemoglobin 120 g/L

Activated partial thromboplastic time 81 seconds
Bleeding time within normal ranges
A. Haemophilia A
B. Haemophilia B
D. Thrombotic thrombocytopenic purpura
E. Idiopathic thrombocytopenic purpura
ANSWER:
Haemophilia A
EXPLANATION:
The prolonged aPTT supports the diagnosis of haemophilia.
Between both haemophilia A and B, haemophilia A is more common and it accounts for
90% of cases of haemophilia.
Q-76
A 52 year old lady has been suffering from chronic rheumatoid arthritis and is on
methotrexate and naproxen. Her blood results show:
Haemoglobin 83 g/L
What is the SINGLE most likely cause?
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A. Haemorrhoids
B. Gastrointestinal haemorrhage
C. Menorrhagia
D. Folate deficiency
E. B12 deficiency
ANSWER:
Gastrointestinal haemorrhage
EXPLANATION:
Gastrointestinal haemorrhage would be a cause of microcytic anaemia like in the given
scenario and it fits with the history of prolonged use of NSAIDS.
Folate and B12 deficiency are in the category of macrocytic anaemias.
There should be no reason for menorrhagia. Besides, the patient is 52 years old. The
average age of menopause in UK is 51. Blood loss from the gastrointestinal (GI) tract is
the most common cause of iron deficiency anaemia in postmenopausal women.
There is also no relation with haemorrhoids
Q-77
A 39 year old pregnant woman who is 36 week gestation has acute abdominal
pain and is rushed for immediate C-section. Her blood pressure was reported to
be 110/60 mmHg. Her blood tests show:
Haemoglobin 101 g/L

Fibrinogen 0.6 g/L
A. Pregnancy induced hypertension

C. HELLP syndrome
D. Acute fatty liver
E. Obstetric cholestasis
ANSWER:
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EXPLANATION:
Acute abdominal pain may indicate concealed abruptio placentae which may be a
cause of disseminated intravascular coagulation.
The two top choices here are HELLP syndrome and disseminated intravascular
coagulation (DIC). It is important to understand that HELLP syndrome may lead to
disseminated intravascular coagulation. But the more specific answer in this question is
DIC because in HELLP syndrome, the prothrombin time, activated partial
thromboplastin time and serum fibrinogen levels are normal but are prolonged in DIC.
Bilirubin levels may be higher than normal due to bilirubin production

secondary to haemolysis.
Q-78
A 55 year old man complains of headache and visual disturbances. He has a
history of hypertension. He also reports itching after a hot bath and burning
sensation in his fingers and toes. He is noted to have mass in the left upper
quadrant. Blood report shows the following:
Haemoglobin 202 g/L

Eyrthropoeitin is normal
A. Myelofibrosis
B. Polycythaemia rubra vera
C. Essential thrombocythemia
D. Chronic myeloid leukaemia
E. Chronhic lymphocytic leukaemia
ANSWER:
Polycythaemia rubra vera
EXPLANATION:
The signs and symptoms are consistent with polycythaemia rubra vera (PRV)
Hypertension is found in 30% of patients with PRV. Splenomegaly is found

in 75% of patients at the time of diagnosis.
The mass in the left upper quadrant represents the spleen (splenomegaly)
Burning sensation in fingers and toes, are characteristic.
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PCV is usually associated with a low serum level of the hormone erythropoietin (EPO).
However, everything else in this question points towards PRV.
Q-79
A 4 year old boy has a history of epistaxis. Prothrombin time, bleeding time,
fibrinogen levels and von Willebrand factor are normal. Activated partial
thromboplastin time (APTT) was found to be prolonged. His blood tests show:
Haemoglobin 112 g/L

A. Haemophilia
B. Idiopathic thrombocytopenic purpura
C. Sickle cell anaemia
D. Haemolytic uraemic syndrome
E. Thalassaemia
ANSWER:
Haemophilia
EXPLANATION:
Despite the fact that many people remember haemophilia presenting with bleeding into
joints and muscles, you would need to know that epistaxis may occur in haemophilia
Activated partial thromboplastin time (APTT) that is prolonged with everything else
being normal points towards haemophilia.
Factor VIII and IX levels should be offered to confirm the diagnosis.
Q-80
A 53 year old lady has been suffering from chronic rheumatoid arthritis and is on
methotrexate. Blood results show:
Haemoglobin 83 g/L
What is the SINGLE most likely cause?
A. Haemorrhoids
B. Anaemia of chronic disease
C. Menorrhagia
D. Folate deficiency
E. B12 deficiency
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ANSWER:
Anaemia of chronic disease
EXPLANATION:
The patient has microcytic anaemia which can fit with the diagnosis of anaemia of
chronic disease. In anaemia of chronic disease, red cells are often normochromic,
normocytic, but may be hypochromic, microcytic (as frequently seen in rheumatoid
arthritis and Crohn's disease)
Folate and B12 deficiency are in the category of macrocytic anaemias.
There should be no reason for menorrhagia. Besides, the patient is 53 years old. The
average age of menopause in UK is 51.
There is also no relation with haemorrhoids.
Q-81
A 36 year old woman has massive bleeding from a venipuncture site. Petechiae
was noticed on her skin. Her blood tests show:
Haemoglobin 113 g/L

Prothrombin time, activated partial thromboplastin time and bleeding time are
prolonged. Fibrin degradation products were elevated. What is the SINGLE most
likely diagnosis?
A. Haemophilia
C. Idiopathic thrombocytopenic purpura
D. Factor V Leiden
E. Warfarin overdose
ANSWER:
EXPLANATION:
Please see Q-24
Q-82
A 40 year old man has a mild fever and feels generally tired. He has marked
weight loss over the last 6 months and has a bilateral white, vertically corrugated
lesion on lateral surfaces of the tongue. What is the SINGLE most likely
diagnosis?
A. C1 esterase deficiency
B. Crohn’s disease
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C. HIV disease
D. Sarcoidosis
E. Sjogren’s syndrome
ANSWER:
HIV disease
EXPLANATION:
The white, vertical lesion described is called hairy leukoplakia which occurs primarily in
HIV-positive individuals.
Hairy leukoplakia
Hairy leukoplakia is a condition that is characterised by irregular white patches on the
side of the tongue and occasionally elsewhere on the tongue or in the mouth. It is a
form of leukoplakia, which refers to white patches on the mucous membranes of the
mouth often arising in response to chronic irritation. Hairy leukoplakia occurs primarily in
HIV-positive individuals.
This white lesion cannot be scraped off. The lesion itself is benign and does not require
any treatment.
Q-83
A 14 year old child has recurrent throat infections. He feels tired and lethargic all
the time. Blood results show:
Hb 7.2 g/dl
WCC 6 x 109/L
Blood film shows blast cells. What is the SINGLE most likely diagnosis?

ANSWER:
EXPLANATION:
Please see Q-3
Q-84
A 26 year old businessman travelled from New York to the UK. He presented to
A&E three weeks later complaining of drenching night sweats, fever and
lymphadenopathy in the neck since returning from his business trip. What is the
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SINGLE most likely diagnosis?
A. Tuberculosis
B. Lymphoma
C. Aplastic anaemia
D. Hereditary spherocytosis
E. Infectious mononucleosis
ANSWER:
Lymphoma
EXPLANATION:
The two main contenders for an answer to this question are tuberculosis
and lymphoma.
Tuberculosis is improbable because New York City (USA) is not a tuberculosis prone
area. The main TB prone areas that you have to take note of for the PLAB exam is a
patient travelling to or from South Asia or sub-Saharan Africa.
While it is true that the signs and symptoms of tuberculosis and lymphoma are very
similar, the following table makes is easy to differentiate between tuberculosis and
lymphoma if you are having difficulty choosing either as an answer:
Tuberculosis Lymphoma
Fatigue, malaise, fever, weight loss, Drenching night sweats, fever, weight loss
anorexia
Hilar, paratracheal or superficial node Enlarged but otherwise asymptomatic
involvement. Palpable nodes may be lymph node, typically in the lower neck or
initially tender, firm and discrete supraclavicular region
Chronic, productive cough with purulent +/- Patients might complain of chest
bloodstained sputum discomfort with a cough or dyspnoea
May result in lobar collapse, Mediastinal masses are frequent and are
bronchiectasis, pleural effusion and sometimes discovered on a routine CXR
pneumonia
Erythema nodosum Findings on examination include
lymphadenopathy, hepatomegaly,
splenomegaly, and superior vena cava
syndrome
Q-85
A 54 year old man has fatigue. A recent blood report shows the following:
Haemoglobin 90 g/L
Serum ferritin 9 micrograms/L
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Total iron-binding capacity 75 micromol/L
A. Thalassaemia trait
B. Hypoparathyroidism
C. Hereditary sideroblastic anaemia
E. Iron deficiency anaemia
ANSWER:
Iron deficiency anaemia
EXPLANATION:
Iron-deficiency anaemia
Aetiology
• Blood loss from the gastrointestinal (GI) tract is the most common cause of iron-
deficiency anaemia in adult men and postmenopausal women
• Blood loss due to menorrhagia is the most common cause of iron deficiency in
premenopausal women
• In tropical countries, infestation of the gut may cause irondeficiency anaemia ,
especially with hookworm and schistosomiasis
• Common causes of blood loss include:
• Non-steroidal anti-inflammatory drug (NSAID) use
• Colonic carcinoma
• Gastric carcinoma
• Gastric or duodenal ulceration
• Dietary inadequacy
• Failure of iron absorption: Malabsorption conditions such as coeliac disease
• Excessive requirements for iron: Pregnancy
Laboratory tests
• Low Haemoglobin
• Low Mean cell volume (MCV)
• Low Mean cell haemoglobin concentration (MCHC)
• High Red cell distribution width (RDW)
• Low serum ferritin
• High Total iron-binding capacity
The above laboratory tests are important to remember for PLAB as they may be asked
Q-86
A 15 year old girl was admitted with chest infection. She was treated and her
symptoms had regressed. She was brought again with fever and the same
symptoms a few days later. It was found that all her blood works done in the
hospital showed a mild anaemia and thrombocytopenia. What is the SINGLE
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A. Acute myeloid leukaemia (AML)
B. Acute lymphoblastic leukaemia (ALL)
C. Aplastic anaemia
E. Chronic myeloid leukaemia (CML)
F. Chronic lymphocytic leukaemia (CLL)
ANSWER:
EXPLANATION:
The age is th3e only factor that support the diagnosis of acute lymphoblastic leukaemia
(ALL) along with the given picture. The same picture can happen in aplastic anaemia
but there is not a single factor mentioned in favour of it. So acute lymphoblastic
leukaemia (ALL) can be taken as best option in the given scenario.
Q-87
A 36 year old female presents with a petechial rash and menorrhagia. Her
physical examination is completely normal and she has no other complaints. A
full blood count was done and reveals:
Hb 13.3 g/dL
WBC 9 x 109/L
A. Polycythaemia rubra vera

B. Thrombocytopenia
C. Thrombocytosis
E. Hyposplenism
ANSWER:
Thrombocytopenia
EXPLANATION:
This woman has an isolated decrease in platelets with no other complaints (other than
menorrhagia). The presence of petechiae is an additional clue to thrombocytopaenia.
Q-88
A 33 year old man complains of lethargy tiredness and pruritus. A diagnosis of
polycythaemia vera was made. What is the SINGLE most appropriate
management?
A. Phlebotomy
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B. Splenectomy
C. Indomethacin
D. Heparin
E. Warfarin
ANSWER:
Phlebotomy
EXPLANATION:
Venesection is the most appropriate.
Splenectomy is something to consider in the management of PCV. But it is usually

down the line when there is painful splenomegaly or there are repeated episodes of
splenic infarction.
Q-89
A 25 year old Greek man presents with dark red urine hours after eating fava
beans. He is now very ill and has signs of shock. Spherocytes and red blood cell
fragments are seen on blood film. What is the SINGLE most likely diagnosis?
C. Alpha thalassaemia
D. Beta thalassaemia
ANSWER:
EXPLANATION:
Spherocytes are usually seen in hereditary spherocytosis and autoimmune haemolytic
anaemias. However, they may be seen in G6PD deficiency as well in severe
haemolysis. The history of consumption of fava beans followed by rapid deterioration
points towards G6PD deficiency. Otherwise, in the exam, if you see spherocytes, it is
almost always either hereditary spherocytosis or autoimmune haemolytic anaemias.
Q-90
A 59 year old smoker who recently underwent a hip replacement surgery 2 days
ago, has a swollen and tender left leg. The diameter of his left calf is higher than
the right calf. Passive movements cause pain. The calf is tender to touch. What
is the SINGLE most likely diagnosis?
A. Deep vein thrombosis

B. Lymphoedema
C. Peripheral vascular disease
D. Cellulitis
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E. Superficial thrombophlebitis
ANSWER:
Deep vein thrombosis
EXPLANATION:
One calf having a larger diameter than the other is one one of the known signs of a
DVT. The risk factors (smoker, immobile, major surgery) that are given also point clearly
towards the likely diagnosis of deep vein thrombosis.
Q-91
A 35 year old man has fatigue, night sweats and a mild fever for the last month.
Examination reveals painless cervical lymphadenopathy. Splenomegaly is noted
on abdominal examination. He has signficant weight loss. What is the SINGLE
A. Non-Hodgkin lymphoma
B. Polycythemia
C. Iron deficiency anaemia
D. Toxoplasmosis
E. Cytomegalovirus infection
ANSWER:
EXPLANATION:
There are two major points mentioned here: cervical lymphadenopathy and
splenomegaly.
This combination makes Non-Hodgkin lymphoma as the most likely cause

Toxoplasmosis although uncommon, may have cervical lymphadenopathy and
splenomegaly as well. But weight loss is not seen in toxoplasmosis hence non-
hodgkin's lymphoma remains the top choice.
Q-92
A 52 year old female has lost a few litres of blood during a hysterectomy. She is
due for a blood transfusion. What is the SINGLE most likely test involved in the
preparation of blood transfusion?
A. Indirect Coomb’s test

B. Direct Coomb’s test
C. Sickle cell solubility test
D. G6PD enzyme assay
E. Osmotic fragility test
ANSWER:
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Indirect Coomb’s test
EXPLANATION:
An indirect Coombs test would test patient’s serum rather than red blood cells. This is
appropriate as we would like to identify antigenicity. By doing the indirect Coombs test
we are able to detect antibodies against RBC that are present unabound in the patient’s
serum.
Q-93
A 63 year old man presents with extreme thirst that despite drinking fluids he still
feels thirsty. He has been having a back ache for the last 4 months that is getting
worse and feels tired all the time. During this time, he has noticed weight loss
and mild breathlessness. His serum calcium was found to be elevated. A blood
film was taken. What is the SINGLE most likely finding to be seen on a blood
film?
A. Basophilic stippling
B. Howell Jolly bodies
C. Heinz bodies
D. Trophozoites
E. Rouleaux formation
ANSWER:
Rouleaux formation
EXPLANATION:
The signs and symptoms along with the hypercalcaemia point towards multiple
myeloma. Breathlessness occurs due to anaemia found in multiple myeloma.
Rouleaux formation can be seen on the blood film in multiple myeloma.
Q-94
A 50 year old man presents to his GP with the complaint of shortness of breath.
He describes his shortness of breath as increasing in severity over the past few
months. He is also noted to have a persistent cough. The patient also complains
of lethargy and tiredness which he says started around three months ago. The
patient’s past medical history is signficant for migraine headaches which he
takes non-steroidal anti-inflammatory medications for. He works as a production
manager for a medium sized company and reports no undue stress in his
personal or professional life. He drinks socially and smokes around 20 cigarettes
a day for the past 30 years. A blood test done and the results are as follows:
Haemoglobin 198 g/L

White cell count (total) 9.8 x 109/L
Haematocrit 58%
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What is the SINGLE most useful hormone level to test for to help establish a
diagnosis?
A. Aldosterone
B. Cortisol
C. Erythropoeitin
D. Thyroxine
E. Insulin
ANSWER:
Erythropoietin
EXPLANATION:
This stem shows a diagnosis of secondary polycythaemia due to chronic hypoxia.
Patients who are long term smokers who have an underlying chronic obstructive
pulmonary disease may have polycythaemia as a complication. The long term hypoxia
triggers an increased production of erythropoietin by the kidneys so that it stimulates the
bone marrow cells to produce more red blood cells to transport oxygen to tissue.
Patients can present with non-specific symptoms such as lethargy, tiredness and
headaches.
Other important causes of secondary polycythaemia due to hypoxia include:

• High altitudes
• Cyanotic congenital heart disease
Q-95
A 4 year old boy has a cough and arthritis followed by rash on legs which are
non-blanching on glass test. He has no history of a fever. His blood tests show:
Haemoglobin 120 g/L

A. Meningitis septicaemia
B. Haemophilia
ANSWER:
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EXPLANATION:
The blood results are all normal. The rash in the legs that are non blanching and the
arthritis are hints towards Henoch-Schönlein purpura.
The disease occurs mostly in the winter months. About 50-90% of patients have a
preceding upper respiratory tract infection (URTI) which explains the cough in the given
question.
The stem here gives a no history of fever. Generally, patients with Henoch-Schönlein
purpura appear to be mildly ill, with low-grade fever. But having no fever does not
exclude the diagnosis.
Q-96
A 65 year old man has a routine full blood count which results are as follows:
Haemoglobin 195 g/L

White cell count (total) 7.8 x 109/L
He is a chronic smoker. What is the SINGLE most likely diagnosis?
A. Secondary polycythaemia
B. Polycythaemia rubra vera
C. Essential thrombocythaemia
D. Myelofibrosis
E. Chronic lymphocytic leukaemia
ANSWER:
Secondary polycythaemia
EXPLANATION:
Secondary polycythaemia (more accurately secondary erythrocytosis) is the answer.
Erythrocytosis has many causes which include primary (polycythaemia rubra vera) or
secondary (living at high altitudes, smokers, patients with COPD). The fact that
platelets and white cell counts are within the normal range suggest a secondary cause
rather than polycythaemia rubra vera. Chronic smokers are at risk of developing
secondary erythrocytosis due to chronic hypoxemia which triggers increased production
of erythropoietin by the kidneys.
If repeated haemoglobin is still high in 2 months time, further investigations would be

warranted.
Q-97
An INR result of a 64 year old man was found to be 6.3. The local haematology
laboratory highlighted this finding and informed the clinic. The patient takes
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warfarin for atrial fibrillation. He is otherwise well with no active bleeding. What
is the SINGLE most appropriate diagnosis?
A. Start oral phytomenadione

B. Inform patient to present to the nearest A&E department
C. Stop warfarin and arrange for a repeat INR the following day.
D. Reduce dose of warfarin and repeat INR the following day
E. Reduce dose of warfarin and repeat INR in a week
ANSWER:
Stop warfarin and arrange for a repeat INR the following day
EXPLANATION:
This patient has an INR between 6 and 8 without bleeding. He needs his warfarin
stopped until his INR is less than 5. Cases like these are usually managed in an
anticoagulation clinic. A telephone call to the patient to inform him of his INR result is
appropriate. He does not need to present to A&E.
Phytomenadione is also known as vitamin K1. It is used when the INR is more than 8
or if the patient has a major bleed in the context of warfarin use.
Q-98
An 18 year old boy presents with a lump on his neck which has been enlarging in
size over the few weeks. He feels fatigued and describes frequent night sweats.
He has been told by his family members that he looks thinner over the past
month. He denies recent travels abroad. On examination, he has a 3 cm non-
tender lump in the right side of the neck and an enlarged spleen on abdominal
examination. He has a temperature of 38.4 C. What is the SINGLE most likely
diagnosis?
A. Infectious mononucleosis
B. Lipoma
C. HIV
D. Thyroglossal cyst
E. Hodgkin lymphoma
ANSWER:
Hodgkin lymphoma
EXPLANATION:
This lump is concerning and with the systemic symptoms of night sweats, fever and
weight loss are termed B symptoms. Hodgkin’s lymphoma can occur in the paediatric
population (usually older children). Splenomegaly is seen in 30% of all cases of
Hodgkin’s lymphoma.
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“B” symptoms
• Weight loss of more than 10% of body weight during the previous 6 months
• Unexplained fever
• Drenching night sweats
Another take home point from this question is that Hodgkin’s lymphoma has a bimodal
age distribution. It has two incident peaks. One peak around age 20 to 29 years of age
and another at 60 years of age.
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HAEMATOLOGY

A. Ensure donor is adequately hydrated and has not skipped a meal

Blood film morphology was unremarkable. Reticulocytes are absent. A bone

It is also important to note that the blood film morphology is unremarkable

What is the SINGLE most likely diagnosis?

A. Acute myeloid leukaemia

Acute lymphocytic leukaemia (ALL) is more common in children, and

Many other disorders can present as pancytopenia similar to leukaemiasuch as aplastic

In the exam, look for massive

What is the SINGLE most likely diagnosis?

Haemoglobin 158 g/L (130-180 g/L)

If INR is higher than the target with a major bleed:

WARFARIN AND HIGH INR MANAGEMENT

For major bleeding – stop warfarin, administer intravenous vitamin K1

Hb: 11.0 g/dL

What is the SINGLE best explanation for these blood results?

A. Iron deficiency anaemia

Normal physiological changes in pregnancy

A. G6PD enzyme assay

Direct Coombs test is the investigation of choice.

Types of autoimmune haemolytic anaemia

Warm antibody induced haemolysis

Cold haemagglutinin disease (CHAD)

A. Continue with warfarin

Surgery and Warfarin

Bence-Jones is a protein not a cell.

Rarely, symptoms of a hyperviscosity syndrome such as blurry vision, and confusion,

A peripheral blood smear is significant for polychromasia and scattered

A. Direct antiglobulin test

Direct Coombs test

Indirect Coombs test

Direct Coombs test Indirect Coombs test

How the test works: How the test works

Acute lymphoblastic leukaemia (ALL)

Acute lymphocytic leukaemia (ALL) is more common in children, and acute

Haemoglobin 109 g/L

What SINGLE investigations is most likely to lead to a diagnosis?

Electrophoresis is already performed in this quesiton as monoclonal proteins can only

Thrombophilia is not required for investigation of patients with superficial

Treatment for superficial thrombophlebitis evolves around

Prevention of deep venous thrombosis and pulmonary embolism

Are ultrasounds needed?

Are D-dimers required?

What are megaloblastic anaemias?

A. Thrombotic thrombocytopaenic purpura

Henoch-Schönlein purpura (HSP) Vs Haemolytic uraemic syndrome (HUS) Vs

Henoch-Scholein Purpura Haemolytic Uraemic Syndrome Thrombotic Thrombocytopenic

Features of IgA nephropathy may

Seen in Children Seen in Children

Haemolytic uraemic syndrome (HUS)

Signs and Symptoms:

Most adults infected with E. coli O157 remain asymptomatic.

There is often fever, abdominal pain and vomiting

Important points to know:

Management for thalassaemia major:

Blood report shows the following:

Philadelphia chromosome was positive on cytogenetic analysis. What is the

A. Acute lymphoblastic leukaemia (ALL)

Note that platelets can be normal in CML.

Chronic myeloid leukaemia (CML)