OLFU Red Blood Cell Disorders Part 1

CLINICAL HEMATOLOGY 1 LEC 9 2021 – 2022

1st Semester
RMT 2023 Instructor: Prof. Antonio C. Pascua, Jr., RMT, MSMT TRANS 10 HEMA311
Date: December 9, 2021 LEC

Outline
At the end of the session, the student must be able to learn:
I. Anemia
A. Causes of Anemia
B. Clinical Signs and Symptoms
C. Classification of Anemia
II. Microcytic – Hypochromic Anemia
A. Iron Deficiency Anemia
A. Etiology
B. Anemia of Chronic Disease
A. Pathophysiology
B. Laboratory Findings
C. Sideroblastic Anemia
III. Normocytic – Normochromic Anemia
A. Aplastic Anemia
A. Pure Red Cell Aplasia
B. Hemolytic Anemia
A. Intrinsic Hemolytic Anemia
1. Types of Intrinsic Hemolytic Anemia
A. Extrinsic Hemolytic Anemia ❖ Anemia may be a sign of an underlying disorder
1. Types of Immune Extrinsic Hemolytic ❖ Dilutional Anemia with normal or increased total red cell mass
Anemia may occur with pregnancy, macroglobulinemia and splenomegaly
2. Types of Non-Immune Extrinsic Hemolytic
Anemia B. Clinical Signs and Symptoms of Anemia

I. ANEMIA ❖ Diminished delivery of oxygen to the tissues

❖ Clinical signs reflect the rate of reduction of hemoglobin and blood
➢ Reduction of red cell mass (hemoglobin content) volume
➢ Decreased concentration of hemoglobin (inability of the RBC ➢ If anemia develops slowly in a patient who is not otherwise
to deliver oxygen to the tissues) severely ill, a hemoglobin concentration of as low as 6 g/dL
➢ Screen/ Identify individuals at risk for anemia and the first may develop without producing any discomfort or physical
parameter need to check is hemoglobin signs if the patient is sedentary
▪ <12g/dL = anemia ❖ General Manifestations
❖ Relative: ➢ Vertigo, faintness, headache and heart palpitations
➢ Normal RBC mass, volume is low ❖ Physical Expressions of Anemia
▪ E.g.: dehydration (the amount of blood/water circulating ➢ Pallor, low blood pressure, a slight fever, and some edema
in the body is low = less delivery of oxygen on the
tissues) Signs and Symptoms
➢ Transient (temporary)
➢ Normal retics • Easy fatigability
❖ Absolute: • Dyspnea on exertion
➢ “True anemia” • Bounding pulse
➢ Low RBC mass, normal volume
• Palpitations
➢ Low RBC delivery to circulation
- Less delivery of oxygen → heart will pump more
▪ Problem in the production of RBC (bone marrow failure)
• Systolic murmur
➢ Loss of RBC from circulation
▪ Destroying the red cells because of parasitic infection in • Faintness and vertigo
the blood • Pallor
• Low BP
A. Causes of Anemia • Headache
• Spoon nails
❖ Anemia
➢ Considered to be present if the hemoglobin concentration
of the red blood cells (RBCs) or the packed cell volume of
❖ Evaluation of Anemia
RBCs (hematocrit) is below the lower limit of the 95%
➢ Red cell count
reference interval for the individual’s age, gender, and
➢ Red cell indices (MCV, MCH, MCHC)
geographical location
▪ Help in classification of anemia
❖ Three Major Pathophysiological Features of Anemia
▪ MCHC = specific for anemia
➢ Blood loss
➢ Hemoglobin and hematocrit
➢ Impaired red cell production
▪ First screening tool
➢ Accelerated red cell destruction (hemolysis in excess of the
➢ RDW
ability of the marrow to replace these losses)
▪ Degree of anisocytosis
▪ How much red cells vary in size and shape
➢ PBS (Peripheral Blood Smear)
▪ Qualitative description of the appearance of the blood
cells
▪ Confirms the size, color and shape of the cells as well as
the maturity of the red cell
➢ Reticulocyte Count
▪ Assess erythropoietic activity of the bone marrow
▪ Index or RBC production
Surell, R. – TRANSCRIBER
[HEMA311] 3.01 Red Blood Cell Disorders I Prof. Antonio C. Pascua, RMT, MSMT

➢ OFT (Osmotic Fragility Test) ❖ Causes:

▪ Capability of red cells to resist lysis ➢ Dietary inadequacy
▪ Hereditary spherocytosis ▪ Source of iron: green leafy vegetables
➢ Bone Marrow Examination ➢ Malabsorption
▪ Number of red cells are high or low, check always the ▪ Problem with the absorptions of nutrients in the system
bone marrow (because RBCs are synthesized from the ➢ Increase iron loss
bone marrow) ▪ Bleeding (menstruation)
▪ Number of circulating RBC ➢ Increased iron requirement
▪ Need to synthesize more iron because of dehydration
C. Classification of Anemias ➢ Parasitic Infection (Hookworms)
❖ Note:
❖ Classification of Anemia ➢ Iron and Protoporphyrin IX are important component of heme
➢ Physical Characteristics ❖ Laboratory Findings
▪ Degree of Hemoglobinization: diameter of central pallor ➢ CBC: decreased hemoglobin
▪ Size of red cells ➢ Retics: low to normal
▪ Microcytic-Hypochromic: problem in hemoglobin ➢ Reticulocyte count
(decrease) ▪ Equal or greater than 2.5% demonstrates increased
▪ Normocytic-Normochromic: problem in the production of erythropoiesis (e.g., acute bleeding,
RBC (decrease) hemoglobinopathies, or hemolytic anemia)
➢ Pathogenesis ▪ Less than 2.5%, the red blood cell indices can form the
▪ Disorders of red cell formation algorithmic basis for separating anemias into categories
▪ Excessive loss of red cell ➢ OFT: decreased
▪ Abnormal distribution of red cells ▪ Increased pallor area (not easily lysed)
➢ Red Cell Indices
II. MICROCYTIC – HYPOCHROMIC ▪ Decreased MCV, MCH and MCHC
➢ Platelet Count
❖ Failed to synthesize normal hemoglobin content ▪ Usually normal but may be increased following acute
❖ Small and pale blood loss
❖ TICS ➢ Leukocyte Count
➢ Thalassemia ▪ Usually normal
➢ Iron Deficiency Anemia ➢ Bone Marrow:
➢ Chronic Disease ▪ Marked decrease in stable iron and erythroid h
➢ Sideroblastic Anemia yperplasia
➢ Others:
A. Iron Deficiency Anemia (IDA) ▪ Decreased serum iron
• Serum iron% saturation is not a confirmatory for
❖ Most common cause of anemia IDA
❖ Iron ▪ Serum ferritin
➢ Essential element in the synthesis of hemoglobin • Stored form of iron
• Confirm IDA
A. Etiology ➢ Increased:
▪ TIBC
• Total iron binding capacity
❖ Decreased Iron Intake • Store iron as ferritin, since no iron produced, TIBC
➢ A deficiency of this type results when not enough iron is remain high
consumed to meet the normal, daily required amount of iron ▪ FEP
(e.g., fat diets and an imbalanced vegetarian diet) • Free Erythrocyte Protoporphyrin
➢ E.g., Iron deficient diets • Accumulation of Protoporphyrin IX
❖ Increased Iron Utilization
➢ An increased demand for iron that is not met, such as during
pregnancy, the growth years, or periods of increased blood
regeneration
➢ E.g., Postnatal growth spurt and Adolescent growth spurt
❖ Excessive Loss of Iron (Physiological or Pathological Iron
Deficiency)
➢ An excessive loss of iron can result from acute or chronic
hemorrhage or heavy menstruation
➢ E.g., Menstruation and Pregnancy
❖ Faulty or Incomplete Iron Absorption (Physiological Iron
Deficiency)
➢ Conditions of faulty or incomplete iron absorption can be
caused by achlorhydria in certain disorders or following gastric
resection or chronic diarrhea
➢ If a gastroenterologic evaluation fails to disclose a likely cause
of IDA, or in patients refractory to oral iron treatment,
screening for celiac disease, autoimmune gastritis, and
Helicobacter pylori is recommended
➢ E.g., Autoimmune gastritis, Celiac disease, H. pylori infection
❖ Pathological Iron Loss in Adult Males and Postmenopausal
Females with Iron Deficiency
➢ An evaluation of abnormal occult bleeding, especially
gastrointestinal (GI) bleeding, is needed
➢ E.g., Gastrointestinal bleeding, Urogenital bleeding,
Pulmonary hemosiderosis, Intravascular hemolysis,
Malignancy (colon cancer)
Surell, R. – TRANSCRIBER
[HEMA311] 3.01 Red Blood Cell Disorders I Prof. Antonio C. Pascua, RMT, MSMT

B. Anemia of Chronic Disease ➢ Normal or increased bone marrow iron stores are observed
within macrophages
❖ It is the second most prevalent anemia after IDA ➢ Patients with AOI caused by Malignancy:
❖ Common complication in patients with disorders as diverse as ▪ Leukoerythroblastosis the presence of both immature
inflammation, infection, malignancy or various systemic diseases erythrocytes and leukocytes
❖ Half of AOI/ACD cases are caused by subacute or chronic ➢ Abnormal Erythrocyte Morphology
infections such as tuberculosis, lung abscess and bacterial ▪ Teardrop, schistocytes, helmet cells, fibrosis and
endocarditis. Other cases may be caused by neoplasms, hypochromia
rheumatoid arthritis, rheumatic fever, systemic lupus ❖ Leukocyte Count
erythematosus, uremia and chronic liver disease ➢ Consistent with the type and degree of infection present in the
❖ Due to chronic infections, inflammatory process and malignant patient
neoplasms ❖ Platelets
❖ Blockage in delivery of iron to the developing red cell ➢ Normal in quantity
❖ Low serum iron (because those iron did not used will be stored as ❖ Bone Marrow
ferritin) and TIBC; High serum ferritin ➢ Hemosiderin is increased or normal
➢ Sideroblasts decreased
A. Pathophysiology ❖ Reticulocyte Count
➢ Less than 2%
❖ AOI/ACD is a hypoproliferative anemia resulting from C. Sideroblastic Anemia
underproduction of red cells
❖ Life span of erythrocytes is mildly shortened in this disorder (in ❖ Abnormalities in heme metabolism
some patients, the erythrocyte survival time is 90 days), decreased ❖ Adequate iron stores but unable to incorporate it into Hgb
erythrocyte survival is not an isolated or major factor in the ❖ There is iron but do not have protoporphyrin IX inside = iron
development of anemia accumulated in the cell
❖ The principal pathogenesis of ACD is believed to be related to a ➢ Loss of protoporphyrin IX
recently describe molecules, hepcidin ❖ Presence of nucleated RBC with iron granules
➢ Hepcidin is released by the liver and circulates to interact with ❖ Stain: Prussian blue
its cellular receptor, the iron export channel ferroportin, to ❖ Can be hereditary – sex linked (rare)
block release of iron from cells (e.g., tissue macrophages and ❖ Primary
jejunal enterocytes) ➢ Idiopathic
➢ Hepcidin is able to induce iron sequestration and ❖ Secondary
hypoferremia ➢ Associated with leukemia or disorders with hemoglobin
➢ Hepcidin blocks cellular efflux by binding to and inducing the synthesis (lack of vitamin B12/folic acid or exposed to lead
degradation via internalization of ferroportin at the level of poisoning)
both enterocytes and macrophages of the mononuclear ❖ Laboratory Findings
phagocytic system (MPS). Excessive production of ➢ RDW increased
hepcidin results in MPS iron blockage and a defective iron ➢ Hypercellular BM
supply for erythropoiesis, and defective endogenous ➢ Normal retics
erythropoietin production, which results in anemia ➢ High: serum iron, serum ferritin and LDH
❖ Characteristics of Anemia of Inflammation associated with ➢ Positive Stain: Prussian blue/perls stain
Malignancy can be: ➢ Papennheimer bodies on Giemsa
➢ Inadequate production of erythropoietin (EPO) in response to
anemia Table 1: Comparison of the 3 Types of Anemia
➢ Inadequate response of the erythroid marrow to endogenous
EPO Serum TIBC Serum FEP RDW
➢ Impaired release of iron due to increased hepcidin production
Iron Ferritin
producing a functional iron deficiency
IDA Low High Low High High
➢ Alterations in production of several proinflammatory cytokines
Chronic Low Low High High Normal
➢ Decreased erythrocyte production because of direct bone
Disease
marrow infiltration by malignant tumor cells or by primary
marrow cell malignancies Sideroblastic High Normal High Low High
➢ Increased erythrocyte destruction present in immune or
microangiopathic hemolytic anemia III. NORMOCYTIC – NORMOCHROMIC
➢ Acute or chronic blood loss
➢ Toxic effects of invasive therapy (e.g., chemotherapy or ❖ Normal in size and color
radiation therapy) ➢ 6-8um diameter
➢ Indirect multiple causes such as anemia associated with ➢ 1/3 pallor area
malignant disease, anemia associated with major organ ❖ Decreased number of red blood cells in the circulation
failure, and various hemolytic anemia ❖ Types
➢ Aplastic Anemia
➢ Hemolytic Anemia
B. Laboratory Findings ➢ Renal Disease
➢ Acute Blood Loss
❖ Hematocrit
➢ 28% to 32% range A. Aplastic Anemia
➢ Uremia: hemoglobin 5g/dL
❖ Peripheral Blood Smears ❖ Aplastic
➢ Normochromic and normocytic erythrocytes ➢ Total absence of cells within the bone marrow
❖ RBC Abnormalities ➢ Associated with pancytopenia (all of the blood cells count are
➢ An ACD patient with normochromic and normocytic red cells low including reticulocyte)
may be suffering from conditions such as autoimmune ➢ Hypocellular bone marrow (no hematopoietic cells in the bone
disorder or chronic renal disease marrow)
➢ A compensatory erythroid hyperplasia of the bone marrow or
reticulocytosis is not present

Surell, R. – TRANSCRIBER
[HEMA311] 3.01 Red Blood Cell Disorders I Prof. Antonio C. Pascua, RMT, MSMT
❖ Structural Membrane Defects
❖ Associated with: ➢ The ability of erythrocytes to deform and subsequently return
➢ Drug exposure to their biconcave disc shape is determined by:
▪ Chloramphenicol (antibiotics that may damage bone ▪ Flexibility of the membrane, which relies on the structural
marrow), sulfonamides and functional integrity of the membrane skeleton
➢ Viral infections ▪ Cytoplasmic viscosity determined primarily by
▪ Parvovirus B19, cytomegalovirus, EBV hemoglobin
➢ Exposure to toxins ▪ Cell surface-area to volume ratio
▪ Benzene, pesticides, herbicides, exposure to radiation or
chemotherapy (after chemo, mostly patients undergo Table 2: Examples of Inherited Hemolytic Anemias
blood transfusion) Structural Erythrocytic Defects of the Hgb
➢ Tuberculosis Membrane Defects Enzyme Defects Molecule
➢ Chemicals Acanthocytosis G6PD deficiency Hb C disorder
➢ Common among 50 years old and above Hereditary Glutathione Hb S-C disorder
▪ 50% diagnose with aplastic anemia = 6 months mortality Spherocytosis reductase
rate Hereditary Hexokinase Hb S-S disorder
❖ Severe if 3 of the 4 criteria are present: Elliptocytosis (sickle cell anemia)
➢ Neutrophil count: <500/uL Hereditary Pyruvate kinase Thalassemia
➢ Platelet count: <20000/uL Stomatocytosis
➢ Reticulocyte count: <10000/uL Hereditary
➢ Markedly hypocellular marrow Xerocytosis
❖ Treatment:
Rhnull disease
➢ Bone marrow transplantation
1. Types of Intrinsic Hemolytic Anemia
A. Pure Red Cell Aplasia
❖ Hereditary Spherocytosis
❖ Hypoplasia of Erythrocyte precursors only with normal myeloid and ➢ Very heterogenous form of hemolytic anemia transmitted in
platelet elements the majority of cases as an autosomal dominant trait
❖ Severe anemia with reticulocytopenia ➢ Manifestations of the disorder range from almost normal
❖ Associated with carriers of the trait to cases of severe hemolytic anemia
➢ Hemolytic anemia, parvovirus infection, drugs, thymoma ➢ Causes:
➢ Diamond Blackfan Syndrome = congenital form ▪ Deficiency in spectrin or thermal injury (RBC were
exposed to high temperature = loss of pallor area)
B. Hemolytic Anemia ▪ Increased temperature
▪ Results from the loss of erythrocytic membrane surface,
❖ The common denominator in hemolytic anemia is an increase in as vesicles due to membrane protein defects
erythrocyte destruction initiated primarily by trapping of cells in ➢ Hemolysis is extravascular, occurring only in the presence of
sinuses of the spleen or liver and producing a decrease in the the spleen
normal average life span of the erythrocyte ➢ A deficiency of spectrin and defective binding of spectrin to
❖ When the bone marrow fails to increase the production of band 4.1 or some other cytoskeletal abnormality may be
erythrocytes to offset the loss of cells caused by hemolysis, anemia present
develops ➢ Spherocytic cells demonstrate an abnormal permeability to
❖ If red cells are lysed all contents of red cells will come out = sodium ion (Na+), causing an influx of sodium at 10 times the
enzymes LDH, K elevated in blood normal rate
❖ Best procedure to check = counting retics ➢ Loss of red cell membrane resulting in decreased surface
❖ Lysing/destroying red cells area → susceptible to lysis
❖ Shortened red cell survival (lead to destruction or lysis of RBC) ➢ OFT: Cells are less deformable
❖ Intracorpuscular or extracorpuscular defects ➢ Test:
❖ Classification ▪ OFT: elevated
➢ Intrinsic ➢ Clinical Features
▪ e.g., spherocytic RBC (no enough pallor area) = ▪ Jaundice, splenomegaly, skeletal abnormalities, chronic
susceptible to lysis leg ulcers, gall stones, spherocytes and stomatocytes in
▪ lyse within the red cells itself PBS
➢ Extrinsic ➢ Laboratory Findings:
▪ Healthy and normal red cells, but there are external ▪ Increased: OFT (increased in Hereditary spherocytosis
factors that destroys RBC or Autoimmune hemolytic anemia = to confirm, Coombs
• e.g., Plasmodium falciparum test), B1, LDH, urobilinogen
➢ Intravascular ▪ Decreased: Haptoglobin
▪ Red cells are lysed while inside the blood vessels ▪ MCHC
➢ Extravascular • Greater than 36%
▪ Red cells are lysed outside the blood vessels • Spherocytes are responsible for an increased
❖ Reticulocyte count MCHC
➢ To check for bone marrow response ❖ Hereditary Elliptocytosis
➢ Inherited disorder
A. Intrinsic Hemolytic Anemia ▪ Usually transmitted by a single (dominant) autosomal
gene
❖ Also known as Inherited hemolytic disorders ▪ Homozygous form, it may produce a severe hemolytic
❖ Hereditary Defects anemia in infancy
➢ Abnormalities of red cell membrane (elliptocytosis, ▪ Heterozygous form may show hemolysis
spherocytosis) ➢ Defective membrane protein skeleton structure (protein band
➢ Inherited RBC enzyme defect 4.1), elongated elliptical cells
➢ Disorders of Hgb production (hemoglobinopathies) ➢ Variant: Hereditary pyropoikilocytosis
❖ Acquired Defects ➢ The majority of Hereditary elliptocytosis associated defects
➢ PNI (paroxysmal nocturnal hemoglobinuria) occur in spectrin, the principal structural component of the red
cell membrane skeleton
Surell, R. – TRANSCRIBER
[HEMA311] 3.01 Red Blood Cell Disorders I Prof. Antonio C. Pascua, RMT, MSMT
• Patient RBC + ABO compatible serum (if patient is
❖ G6PD Deficiency type A = type A serum) + sucrose
➢ X-linked disorder • Lysis: patient has paroxysmal nocturnal
➢ Inability to neutralize oxidation stress hemoglobinuria
▪ Involved in pentose-phosphate pathway/hexose- • Excessive hemolysis when exposed to low ionic
monophosphate shunt → glutathione strength solution
▪ If protein is denatured = loss ability to delivery cells ▪ Confirmatory: Ham’s Acid Hemolysis Test
▪ Aging cells • 3 Tubes:
➢ Hemoglobin molecule is unstable, susceptible to hemolysis • Patient RBC + ABO compatible serum + 0.2N HCl
➢ Hemoglobin denatured (Heinz bodies) → inability to carry (weak acid)
O2 • Patient RBC + own serum + 0.2N HCl (rule out
➢ Rapid intravascular destruction autoimmune hemolytic anemia)
➢ Reducing NADPH and glutathione • Patient RBC + inactivated serum (no complement =
➢ Resistant to plasmodium infections heat 56C) + 0.2 HCl
➢ Clinical Patterns
• Hemolysis: tube 1, tube 2 but no Hemolysis in tube
▪ Neonatal jaundice
3
▪ Congenital hemolytic anemia
▪ Drug-induced hemolysis
• Primaquine B. Extrinsic Hemolytic Anemia
▪ Favism
• Consume “fava” beans results to oxidative stress → ❖ Non-Immune
lysis ➢ Transient forceful contact of the body with hard surfaces (e.g.,
• Mediterranean enzyme variant tri-athletes, boxers)
➢ Classes of G6PD Deficiency ➢ Mechanical Trauma
▪ Class I: Severe Deficiency ▪ Chemicals, drugs, snake venom, prosthetic valves
• Hemolysis is chronic (Waring Blender Syndrome)
▪ Class II: Severe Deficiency ➢ Microangiopathic
• Intermittent hemolysis ➢ Chemical and toxic agents
▪ Class III: Mild Deficiency ➢ Infections
• 10 to 60% lysis ▪ Damages RBC membrane (C. perfringens)
➢ Laboratory Diagnosis ➢ Hypersplenism
▪ Inclusion Body ➢ Systemic disease
• Increased: retics, bilirubin, serum LDH ❖ Immune
➢ Antibodies
• Hemoglobinuria
▪ Autoimmune
• Decreased: haptoglobin
• Produce antibodies in own
 RBC lysed → release Hgb → bind with
▪ Alloimmune
haptoglobin → phagocytized
• From other individual
▪ Negative Coomb’s test
▪ Confirmatory: G6PD assay, fluorescence assay (no • Incorrect transfusion of blood
fluorescence = deficient G6PD activity) ➢ Autoimmune Hemolytic Anemia (AIHA) associated with
▪ Ascorbate Cyanide Test cold antibody (IgM)
▪ Due to IgM cold reactive antibodies (<32C)
• Non-specific test for G6PD
▪ Infection, malignancy, autoimmune disorder
• Sodium cyanide and sodium ascorbate and solution
➢ Laboratory Findings
will remain red indicates that the red cells are not
▪ Direct antiglobulin test is positive
lyse. Solution turns brown, indicates that the red
▪ Cold agglutinin titer is increased
cells are lysed because of the stressors
• anti-I
❖ Pyruvate Kinase Deficiency  Mycoplasma pneumoniae
➢ Problem in E-M pathway (Embden-Meyerhof) • anti-i
➢ Autosomal recessive disease  associated infectious mononucleosis (EBV)
➢ Failure to generate sufficient ATP results in defective control ➢ Peripheral Smears
of irons ▪ Polychromatophilia
▪ Na and Ca enters the cell → lysis ▪ Spherocytosis
➢ Jaundice and splenomegaly ▪ Agglutination of red cells
▪ If red cells are lysed = form more bilirubin
➢ Confirmatory Test: PK assay 1. Types of Immune Extrinsic Hemolytic Anemia
➢ Allow sodium and calcium to enter the cell = damage/lysis
❖ Warm Autoimmune Hemolytic Anemia
❖ Paroxysmal Nocturnal Hemoglobinuria ➢ Hemolysis: RBCs react with IgG and/or complement
➢ Proliferation of abnormal clones of hematopoietic cells within ➢ Idiopathic cases
the bone marrow which may be manifested by hemosiderin in ➢ Secondary: caused by lymphoma/leukemia
urine after a night sleep ➢ Laboratory Findings
➢ Hemoglobin granules in the urine ▪ High: OFT, Bilirubin, Reticulocyte
➢ Increased susceptibility to complement mediated red cell lysis ▪ DAT positive
▪ EM: protuberances on the red cell surface ❖ Paroxysmal Cold Hemoglobinuria
▪ Deficiency in DAF (decay accelerating factor → ➢ This is a rare state in which hemolysis occurs when blood is
regulates complement system) warmed after previous exposure to chilling
➢ Red cells are lysed because of increased susceptibility with ➢ Associated with IgG, presence of autohemolysin (Ab) present
complement (once activated will result to lysis) in the plasma → attached to the red cells while in a cold
➢ Chemical abnormalities environment → red cells are warmed → RBC will be lysed in
➢ Deficient acetylcholinesterase activity and abnormally the presence of complement
constituted glycoproteins ➢ Antibody: Anti-P/ Donath Landsteiner Antibody
➢ Laboratory Diagnosis ➢ Laboratory Findings
▪ Screening: Sugar of sucrose lysis test ▪ Elevated reticulocyte count
▪ Increased concentration of indirect bilirubin
Surell, R. – TRANSCRIBER
[HEMA311] 3.01 Red Blood Cell Disorders I Prof. Antonio C. Pascua, RMT, MSMT
▪ Hemoglobinuria
▪ Positive Donath-Landsteiner of Rosenbach or Ehrlich or
Sanford Test
▪ Positive for methemalbumin

➢ Transfusion Reaction
▪ Blood incompatibility
▪ Laboratory Findings: DAT positive, High hemoglobin

2. Types of Non-Immune Extrinsic Hemolytic Anemia

❖ Microangiopathic Hemolytic Anemia (MAHA)

➢ DIC/ Disseminated Intravascular Coagulopathy
▪ Fibrin is deposited in small vessels (unwanted clots)
➢ Hemolytic Uremic Syndrome
▪ Renal damage
➢ Thrombotic Thrombocytopenic Purpura
▪ Deficiency of enzyme ADAMST13 (breakdown of VWF
→ incomplete destruction of blood vessel → clot → RBC
lysed)

References:

• Steininger Clinical Hematology Principles, Procedures,

Correlations
• Turgeon 5th Edition Clinical Hematology Theory and
Procedures
• Lecture Sidenotes of Prof. Antonio C. Pascua, RMT,
MSMT – OLFU VALENZUELA

Surell, R. – TRANSCRIBER