This document defines and classifies haemolytic anaemia. It describes acquired haemolytic anaemia, which can be immune or non-immune. Immune haemolytic anaemia is further divided into autoimmune, alloimmune, and drug-induced types. Warm and cold autoimmune haemolytic anaemias are explained in detail, including their causes, clinical features, laboratory findings, and treatments. Other types of non-immune haemolytic anaemias such as paroxysmal nocturnal haemoglobinuria, red cell fragmentation syndromes, and traumatic cardiac haemolytic anaemia are also summarized.

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