1. HAEMOLYTIC
ANAEMIA

2. DEFINITION
1) Premature destruction of red cells and a
shortened red cell life span below normal 120
days
2) Elevated erythropoietin levels and a
compensatory increase in erythropoiesis
3) Accumulation of hemoglobin degradation
products released by red cell breakdown
derived from haemoglobin

3. CLASSIFICATION

4. ACQUIRED HAEMOLYTIC
ANAEMIA
IMMUNE HAEMOLYTIC ANAEMIA
 These can be subdivided into:
a) Autoimmune
b) Alloimmune
c) Drug-induced

5. AUTOIMMUNE HAEMOLYTIC
ANAEMIA
 warm antibodies bind to RBC most avidly at
370C
 cold antibodies bind best below 320C
Caused by antibodies produced by patient’s own immune
system
Classified according to thermal properties of antibodies:

6. Warm AIHA:
 Antibody usually IgG, but may be IgM or IgA
 CAUSES –
1. alternation in membrane surface antigen
2. Or abnormal response of B lymphocyte
causing auto antibody formation
 May be primary or secondary –
 autoimmune disorders, HIV,
 chronic lymphocytic leukaemia (CLL),
 non-Hodgkin's lymphoma (NHL)
Most common type

7. Incidence:
 Occurs in either sex but female preponderance
reported
 Occurs in all ages
 Higher incidence noted in patients > 45 years

8. Clinical Features:
 Hemolytic anaemia of varying severity
 Tends to remit and relapse
 Haemoglobinurea rare
 Jaundice
 Splenomegaly

9. Laboratory Features:
 Variable anaemia
 Blood film: polychromasia, microspherocytes
 Severe cases: nucleated RBCs, RBC fragments
 Mild neutrophilia, normal platelet count
 Evan’s syndrome: association with ITP
 Bone marrow: erythroid hyperplasia; underlying
lymphoproliferative disorder
 Unconjugated hyperbilirubinaemia
 Haptoglobin levels low
 Urinary urobilinogen usually increased;
haemoglobinuria uncommon

10. Serological Features
 Direct antiglobulin test (DAT; Coomb's test)
usually positive
 Indirect antiglobulin test positive
 RBC may be coated with
1) IgG alone
2) IgG and complement
3) complement only
 Rarely anti-IgA and anti-IgM encountered

11. Treatment:
 Corticosteroids – 1mg/kg daily till Hb stabilizes
 Transfusion
 Splenectomy:
1) patients who fail to respond to steroids
 Immunosuppressive Drugs : severe cases
 Others:
1) plasmapheresis
2) Intravenous immunoglobulin (IVIG) 1g/kg daily for
2days
3) danazol in chronic haemolytic anaemia

12. Cold AIHA:
• Two major types of cold antibody:
1) Cold agglutinins
2) Donath-Landsteiner antibodies
 Causes immediate intravascular destruction of
sensitized RBCs by complement-mediated
mechanisms or sequestration by liver (C3 coated
RBCs preferentially removed here)

13. Cold Agglutinins:
 IgM autoantibodies that agglutinate RBCs
optimally between 0 to 50C. Complement
fixation occurs at higher temperatures
 Primary - Cold Haemagglutinin Disease
(CHAD) or secondary (usually due to
infections) Occurs in male mostly

14. Pathogenesis:
 Specificity usually against I/i antigens
 Bind red cells in peripheral circulation impeding
capillary flow, producing acrocyanosis

15. Clinical Features:
 Chronic haemolysis; episodes of acute
haemolysis can occur on chilling
 Acrocyanosis frequent; skin ulceration and
necrosis uncommon
 Mild jaundice and splenomegaly
 Secondary cases e.g. Mycoplasma, self-
limited

16. Laboratory Features:
 Anaemia- mild to moderate
 Blood film:
a) agglutination, or rouleax
b) spherocytosis less marked than warm AIHA
 DAT +ve: complement only
 Anti-I: idiopathic disease, mycoplasma, some
lymphomas
 Anti-i: infectious mononucleosis, lymphomas

17. Treatment:
 Keep patient warm
 Treat underlying cause
 Alkylating agents: chlorambucil
 Splenectomy and steroids generally not helpful
 Plasmapheresis- temporary relief
 Transfusion- washed packed cells in severe
cases

18. Paroxysmal Cold
Haemoglobinuria
 Rare form
 Characterized by recurrent haemolysis following
exposure to cold
 common due to association with syphilis
 Antibodies usually IgG with specificity for P
antigen
 Biphasic:
a) binds to red cells at low temperatures,
b) lysis with complement occurs at 37C

19. Drug-induced Haemolytic
Anaemia
 May cause immune haemolytic anaemia by
three different mechanisms:
 Neoantigen type e.g. Quinidine
 immune complex mechanism
 Autoimmune mechanism e.g.  -
Methyldopa
 Drug adsorption mechanism e.g. Penicillin
 Hapten mechanism

20. Non-immune haemolytic
anaemias:
 Paroxysmal nocturnal haemoglobinuria (PNH)
 Red cell fragmentation syndromes
 March haemoglobinuria
 Infections
 Chemical and physical agents
 Secondary haemolytic anaemia

21. Paroxysmal nocturnal
haemoglobinuria (PNH)
 Acquired haemopoietic stem cell disorder
 Characterized by
 increased sensitivity of red cells to
haemolysis by complement

22. Pathogenesis:
 Arise as a clonal abnormality of stem cells
 Disorder a consequence of somatic mutations
in synthesis of the
glycosylphosphatidylinositol (GPI) anchor
 Results in deficiencies of several GPI-
anchored membrane proteins –
1) decay accelerating factor (DAF),
2) membrane inhibitor of reactive lysis (MIRL),
3) acetylcholine esterase,
4) leukocyte alkaline phosphatase (LAP)
 These proteins involved in complement
degradation

23. Clinical Features:
 Haemoglobinuria occurs intermittently
 Nocturnal haemoglobinuria uncommon
 Chronic haemolytic anaemia which may be
severe
 Iron deficiency due to loss in urine
 Bleeding may occur secondary to
thrombocytopenia
 Thrombosis a prominent feature

24. Laboratory Features:
 Pancytopenia
 Anaemia may be severe
 Macrocytosis may be present due to mild
reticulocytosis
 Hypochromic, microcytic due to iron deficiency
 Marrow: erythroid hyperplasia; may be aplastic
 Urine: haemosiderinuria constant feature

25. Treatment:
 Transfusion
 Oral iron
 Folate supplements
 Steroids may be of benefit
 Anticoagulation for thrombotic complications

26. Red Cell Fragmentation
Syndromes
 Microangiopathic haemolytic anaemia (MAHA)
 Intravascular haemolysis
 Red cells adhere to fibrin and are fragmented by force of
blood flow in abnormal arterioles.
 Underlying disorders:
 adenocarcinomas
 Complications of pregnancy:
a) Preeclampsia, eclampsia,
 Haemolysis, Elevated Liver enzymes, Low Platelets
(HELLP)
 Disseminated Intravascular Coagulation (DIC)
 Thrombotic Thrombocytopenic Purpura (TTP)/
Haemolytic Uraemic Syndrome (HUS)
 Malignant hypertension

27. Laboratory Findings:
 Blood film:
1) schistocytes prominent,
2) spherocytes,
3) reticulocytes,
4) normoblasts
 Thrombocytopenia
 Coagulopathy in DIC

28. Traumatic cardiac haemolytic
anaemia
 Seen in patients with
1) prosthetic heart valves,
2) cardiac valvular disorders esp. severe aortic
stenosis
 Due to
1) physical damage of red cells from turbulence
2) high shear stresses
 Anaemia usually mild