Samson Hematology
Samson Hematology
Samson Hematology
TOPICS:
1. Anaemia
2. Microcytic Anaemia
3. Iron Deficiency Anaemia
4. Thalassemia
5. Normocytic Anaemia
6. Congenital Spherocytosis
7. Glucose-6-phosphate Dehydrogenase Deficiency
8. Sickle Cell Disease
9. Autoimmune Haemolytic Anaemia
10. Macrocytic Anaemia
11. Pernicious Anaemia
12. Bleeding Disorders
13. Abnormal Coagulation
14. Haemophilia A
15. Haemophilia B
16. Anti-coagulant Therapy
17. Bleeding in liver disease
18. Massive transfusion/cardiopulmonary bypass
19. Abnormal Platelets
20. Thrombocytopenia (ITP)
21. Vascular Defect
22. Malignancies in Haematology
23. Pancytopenia
24. Leukaemias
25. Acute Lymphoid Leukaemia
26. Acute Myeloid Leukaemia
27. Chronic Myeloid Leukaemia
28. Chronic Lymphoid Leukaemia
29. Hodgkins Lymphoma
30. Non-Hodgkins Lymphoma
31. Myeloma
32. Myeloproliferative Disorders
33. Polycythemia Rubra Vera
34. Essential Thrombocytopenia
ANAEMIA
This is low haemoglobin levels.
Parameters for anaemia:
Hb <13.5 g/dl in men
Hb <11.5 g/dl in women
Classification:
1. Microcytic anaemia - MCV <76
2. Normocytic anaemia - MCV 76-96
3. Macrocytic anaemia - MCV >96
Classification depends on the value of MCV. Each type has different causes.
1. Light headedness
2.Tinnitus (ringing in the ear)
3. Pallor
4. Fatigue
5. Weakness
6. Dyspnoea
7. Palpitation
8. Headache
9. Angina
Complications of anaemia:
1. Tachycardia
2. Murmurs (harsh systolic murmur)
3. Heart failure
4. Hyperdynamic circulation
5. Cardiomegaly
A. MICROCYTIC ANAEMIAS
1. IRON DEFICIENCY ANAEMIA
Causes:
1. Chronic blood loss e.g. in bleeding: GIT bleed from use of aspirin/NSAIDs or peptic ulcer or menorrhagia, GIT
malignancy
2. Hookworm infection - caused by Ancylostoma duodenale and Necator americanus. They attach to the walls of the small
intestines causing blood loss which is occult and presents as anaemia. Investigations: FBC for eosinophilia and stool
analysis for ova. Treatment: Albendazole
3. Diet e.g. vegetarian/vegan
4. Malabsorption e.g. Coeliac disease which causes both iron and folate deficiency
5. Inflammatory bowel disease (crohns disease)
Signs:
1. Koilonychias
2. Atrophic glossitis (sore tongue)
Investigation results:
1. Decreased MCV, hypochromia, anisocytosis, poikilocytosis
2. Decreased serum iron
3. Decreased serum ferritin (transport affected)
4. Decreased TIBC (total iron binding capacity) / (no iron)
Treatment:
Oral iron ferrous sulphate for at least 3 months
Any case with Hb < 8 blood transfusion
Any case with Ischemic Heart Disease and Hb <5 blood transfusion
2. THALASSEMIA
This is common in Asian continent like Sri Lanka and Sub Mediterranean continent like Italy, Malta
There is underproduction or no production of Hb peptide chain
Thalassemia major = Hb is usually <9:
There is mutation in - globin genes decreased or absent chain product
Investigations:
Hypochromic, microcytic anaemia (MCV <76)
Target cells
HbF raised
HbA2 variable
HbA absent
Treatment:
Transfusion depending on haemoglobin levels (if Hb <8)
Desferrioxime to prevent iron overload
Splenectomy
Folate supplements
Bone marrow transplants
If no transfusion death may occur.
With transfusion normal development but increased risk of iron overload.
If blood transfusion is not adequate in children anaemia decreased growth skeletal deformity (bossing of the
skull)
After 10 years of repeated transfusions it can lead to endocrine failure, liver failure, heart toxicity (siderosis) due to
accumulation of iron.
B. NORMOCYTIC ANAEMIA
This is anaemia with normal MCV 76-96
CAUSES:
1. Anaemia of chronic disease e.g. polymyalgia rheumatica, rheumatoid arthritis, SLE etc.
2. Bone marrow failure e.g. usually autoimmune (aplastic anaemia)
3. Renal failure is due to reduced production of erythropoietin. In this case you treat anaemia with erythropoietin IM.
4. Pregnancy due to increased demand of iron and folate. Anaemia in pregnancy treat with iron sulphate.
5. Haemolysis usually causes normocytic anaemia but chronic repeated haemolysis can cause microcytic anaemia.
HAEMOLYTIC ANAEMIA
CAUSES:
1. Genetic/Congenital causes (usually young patients or a child)
a. RBC Membranopathies e.g. Spherocytosis, elliptocytosis
b. Haemoglobinopathies e.g. Sickle cell anaemia, thalassemia
c. Enzyme defects eg. G6PD Deficiency
1. Acquired Causes
a. Immune e.g. Haemolytic disease of the newborn, blood transfusion reactions, autoimmune haemolytics anaemia, drug
induced (penicillin, L-dopa)
b. Non-immune eg. Trauma (microangiopathic haemolytic anaemia), infection (septicaemia, malaria), paroxysmal nocturnal
haemoglobinuria
CLASSIFICATION
1. Intravascular haemolysis (takes place in the vessels): free plasma haemoglobin, haemoglobinuria, haptoglobins,
haemosiderinuria.
2. Extravascular haemolysis (takes place in the spleen): There is splenomegaly because the red blood cells are
destroyed in the spleen.
2. Haematuria
3. History of drug intake
4. Previous anaemia
5. Family history
6. Hepatosplenomagaly
7. Leg ulcers (sickle cell anaemia)
Investigations:
Increased bilirubin (unconjugated)
Reticulocytosis (<1% is normal) N.B reticulocytes are young RBC.
Increased urinary urobilinogen polychromasia
Increased haptoglobins (binds free Hb)
Direct Coombs test positive in immune type haemolysis
There is splenomegaly due to extravascular haemolysis. In this condition the red blood cells fail to change their shape as they
pass through the spleen. As a result they get haemolysed by the spleen. There is risk of gallstones.
Investigations:
1. Osmotic fragility test
2. Spherocytes in blood film
Management of crisis:
1. Prompt analgesia (IV opiates) e.g. morphine
2. Give oxygen
3. Cross match blood, Full Blood Count, reticulocytes
4. Check for signs of infection: Blood culture, Chest X-Ray , Mid-Stream Urine
5. Rehydrate by giving normal saline and keep warm
6. Antibiotics if febrile
7. Blood transfusion as required
Investigations:
Hb 6-8g/dl
Reticulocytes 10 20 % (normal reticulocytes is <1%, high reticulocyte count generally means haemolysis of any type)
Increased Bilirubin
Electrophoresis to check the sickle cells
Warm AHA: presents as acute or chronic anaemia. Haemolysis occurs at 37 degrees and above.
Treatment:
1. Steroids
2. Splenectomy
Cold AHA: chronic anaemia gets worse with cold often associated with Raynauds phenomenon
Treatment: keep warm, blood transfusion, chemotherapy, chlorambucil
C. MACROCYTIC ANAEMIA
Causes:
1. Decreased B12
2. Decreased Folate
3. Alcohol
4. Liver disease
5. Pregnancy
6. Haemolysis
7. Hypothyroidism
8. Anti-folate drugs (e.g. phenytoin, methotrexate)
Investigations:
Hypersegmented polymorphs/neutrophils usually found in B12 deficiency.
Target cells (liver disease)
LFT ( increased GGT in alcoholism)
Serum B12
Serum folate
Bone marrow biopsy if the cause cant be found by any of the above tests
If the B12 is then schilling test malabsorption from terminal ileum
NB: alcohol causes high MCV but there is usually no anaemia. Then you can check GGT. It is commonly raised in alcoholism.
1. PERNICIOUS ANAEMIA: This is an autoimmune disease with antibodies to parietal cells and to intrinsic factor. Parietal
cells are in the stomach and they produce intrinsic factor.
Common features:
1. Tiredness
2. Weakness
3. Shortness of breath
4. Paraesthesia/weakness in the limbs due to spinal cord degeneration
5. Atrophic glossitis (sore red tongue)
6. Diarrhoea
Associations:
1. Thyroid disorders
2. Vitiligo
3. Addison s disease
4. Carcinoma stomach
5. Associated with atrophic gastritis which is usually shown by absence of mucosal folding and this usually leads to stomach
cancer
Investigation results:
1. Decreased Hb, MCV > 110, decreased B12, decreased WCC, decreased platelets
2. Hypersegmented polymorphs/ neutrophils
3. Megaloblasts in bone marrow
4. Antibody to parietal cells in 90 % (positive results are not diagnostic)
5. Antibody to intrinsic factor in 60% (are diagnostic if present)
Treatment:
Hydroxycobalamine (B12) IM for 2 weeks every other day
Maintenance IM every 2 months for life
Intrinsic factor binds to B12 in the stomach which protects B12 from being ingested by the hookworms in the
intestine.
COMPLICATIONS:
Sub-acute combined degeneration of spinal cord:
Posterior lateral columns are affected
Triad: extensor plantars + brisk knee jerk + hyper-reflex at ankle
Also there is parasthesia and weakness or ataxia of the limbs (lower limbs)
1.
BLEEDING DISORDERS
General approach
Vascular & Platelet disorders prolonged bleeding + purpura + bleeding from mucous membrane
Coagulation disorder Usually there is bleeding into joints, muscles GI & GU
Therefore normal haemostasis requires the interaction of
a. Platelets
b. Fibrin from clotting cascade
c. Normal microvasculature
A.
ABNORMAL COAGULATION
COAGULATION TESTS
1. PT test for extrinsic system 10, 7, 2, 1 (10 14 sec)
2. INR 0.9 1.2 (PT control), increased INR in warfarin, vitamin K deficiency & liver disease
3. APTT intrinsic system 12, 11, 9, 8 (35 45 sec), increased PTT (heparin, haemophilia (factor 8 affected)
4. Thrombin time 10 15 sec, increased in heparin, increased in DIC
5. Bleeding time (normal 7 min) commonest cause is Von Willebrands disease.
NORMAL VALUES
Prothrombin Time (PT): 10-14 seconds
APTT: 35-45 seconds
Bleeding Time (BT): < 7 min
Thrombin Time (TT): 10-15 seconds
In the GMC exam make sure you use their values as standard normal as sometimes there are variations e.g. an
APTT of 42 may be regarded as high and if you do not use their values you may get a question wrong.
Abnormality
High PT
High APTT
Type of defect
Extrinsic pathway defect
Intrinsic pathway defect
Causes
warfarin, liver disease, vitamin K deficiency
Heparin, haemophilia, Von Willenbrand's disease, lupus anti-coagulant
( anti-phospholipid syndrome
Liver disease, DIC, warfarin
Fibrinogen defect, excess fibrinogen degradation products
Consumption coagulopathy e.g DIC or Liver disease
Von Willenbrand disease ( Also causes high APTT), or acquired platelets
dysfunction, Perform platelets studies if you suspect this.
Deficiency or abnormal fibrinogen or heparin
General Management:
1. Fresh Frozen Plasma - indicated for treatment of
1. HAEMOPHILIA A: Deficiency of Factor VIII, X- linked recessive (only males are affected)
Management:
Avoid I.M injection
In major bleeding give factor VIII
1. ANTI-COAGULANT THERAPY:
Indications:
Deep vein thrombosis
Pulmonary embolism
Atrial fibrillation
Stroke prevention
Prosthetic heart valve
WARFARIN:
Oral
Narrow therapeutic range
Inhibits reductase which is responsible for generating active vitamin K
Management:
INR 5-8 and asymptomatic: does not usually require specific treatment. Only withhold warfarin until INR
less than 5.
INR >8 and asymptomatic: give vitamin K
If there is minor bleeding: give vitamin K
If there is severe bleeding: Requires urgent correction. Prothrombin complex concentrate (II, VII, IX, and
X) is the preferred treatment for life threatening bleeding.
NB. Fresh frozen plasma should only be used if prothrombin complex concentrate not available.
The liver is involved in synthesis of clotting factors II, VII, IX, X which are Vitamin K dependent factors and also vitamin K
Obstructive jaundice: prolonged PT due to vitamin K deficiency
Liver cirrhosis: Increased PT, APTT, and TT; low fibrinogen
Management: Give vitamin K (Fresh Frozen Plasma is more effective as it contains the clotting factors)
ABNORMAL PLATELETS
Causes
1. Increased platelet consumption
Immune
Idiopathic (ITP = Idiopathic Thrombocytopenic Purpura)
Drug induced
SLE
Non Immune
Massive blood transfusion leads to dilutional thrombocytopenia
Hypersplenism (platelets are destroyed in the spleen)
DIC due to increased consumption of platelets
TTP
GENERAL MANAGEMENT
1. For immune mediated thrombocytopenia use steroid e.g. prednisolone with or without immunoglobulin
2. In DIC/massive transfusion = transfuse platelets to keep platelets above 75
Investigations:
Anti platelet Ig G +VE
VASCULAR DEFECTS
Usually this is vasculitis
Congenital:
Osler Weber Rendeu syndrome which is also known as Hereditary haemorrhagic telangectasia (nose bleeds and
mucosal bleeds in GMC scenario)
Acquired:
1. Trauma
2. Vasculitis e.g. in Henoch Schonlein Purpura
3. Scurvy (vitamin C deficiency causing bleeding from gums and usually peri-follicular bleeding)
1.
MALIGNANCIES IN HAEMATOLOGY
a. Leukaemia
i. Acute/Chronic
ii. Lymphoid/Myeloid
b. Lymphoma
i. Hodgkin
ii. Non-Hodgkin
c. Myeloma
d. Myeloproliferative disease
A. LEUKAEMIAS
CLASSIFICATION
LOOK FOR BLOOD FINDINGS: If neutrophils are in the blood its myeloid, if lymphocytes then its lymphoid leukaemia.
Investigations:
1. Blood film shows lymphocytosis
2. Bone marrow biopsy
Treatment:
1) Supportive care blood & platelet transfusion, I.V antibiotics
2) Chemotherapy (main treatment)
Poor prognosis if adult, male, presence of Philadelphia chromosome 9:22, CNS signs, WCC > 100*10*9
2. ACUTE MYELOID LEUKAEMIA (AML):
Anaemia
Infection
Bleeding
Bone pain
CNS sign (cord compression)
Hepatomegaly
Splenomegaly (very common)
Lymphadenopathy
Weakness and malaise
Fever
Gum hypertrophy
Investigations:
WCC variable/high
Blast cell in blood
Bone marrow biopsy
Complications:
Infection
TUMOUR LYSIS SYNDROME due to chemotherapy
Rapid cell death on starting chemotherapy, which causes a rise in serum urate, potassium and phosphate.
Treatment: Initial step is IV fluids, then allopurinol and high fluid intake
Big nodes may cause mass effect: Shortness of breath by compression of trachea
Splenomegaly
Investigations:
Raised WBC >100 x 10^9
Haemoglobin levels are low or normal
Platelets variable
Increased urate (causing renal stones or gout) & alkaline phosphatase
Natural history:
Chronic
Accelerated phase increased symptoms, spleen size
Blast transformation with features of leukaemia
Investigations:
Lymphocytosis
Normocytic normochromic anaemia
Low or normal platelets
Complications:
Auto immune haemolytic anaemia
Infection
Bone marrow failure
Lymphadenopathy
Treatment:
Chemotherapy
Radiotherapy
HODGKIN LYMPHOMA:
Associated with Ebstein Barr Virus
Common in young black patients
Malignant proliferation of lymphocytes (Reed Sternberg cells)
Staging:
I single lymph node
II 2 or more regions on same side of the diaphragm
III both sides of diaphragm
IV > beyond lymph node metastasis
Needs to be differentiated from TB which has tender matted cervical lymphadenopathy and night sweats.
Treatment:
Radiotherapy for I A & II A
Chemotherapy for IIA IV B
MYELOMA:
Malignant proliferation of plasma B-cell
Elderly >70 years of age (typical symptoms include chronic back pain, hypercalcemia, anaemia, proteinuria and raised ESR)
Investigations:
Serum electrophoresis
Urine (Bence Jones protein with paraproteinuria)
Bone marrow (plasma B cell)
X-ray punched out lesion (pepper pot skull)
High Urea and hypercalcemia
Treatment:
Chemotherapy is the main treatment
Analgesia
Transfusion
High fluid intake
Bisphosphonates (control the increase in calcium, & bone pain)
Radiotherapy locally, it decreases the pain if the pain is secondary to bone metastasis.
PANCYTOPENIA
1.
This is when all 3 types of cells are reduced, i.e. low haemoglobin,white cell count and platelets
CAUSES
1. Bone marrow failure e.g. aplastic anaemia
2. Hypersplenism
3. SLE
4. Megaloblastic anaemia
Aplastic anaemia can be caused by drugs like cytotoxic cyclophosphamide, radiation, autoimmune, drugs
(gold), viral hepatitis etc.
1. Infiltration (malignancy, Tuberculosis)
2. Myelofibrosis
Treatment:
Supportive to increase blood count while undertaking definitive which is bone marrow transplant.
5. MYELOPROLIFERATIVE DISORDERS
Classification:
1. Increased RBC Polycythaemia Rubra Vera
2. Increased WBC Chronic Myeloid Leukaemia
3. Increased Platelets Essential thrombocythaemia
4. Increased fibroblasts Primary myelofibrosis
Investigations:
Increased PCV (packed cell volume)
Increased WBC
Blood film
Increased RBC
Increased Platelets
Bone marrow biopsy
Treatment: Chemotherapy
*MYELOFIBROSIS
De-arranged haematopoesis in spleen
Systemic upset
Bone marrow failure