HAEMOLYTIC ANAEMIA

Rahul RantaRoll No.1168

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

CLASSIFICATION

ACQUIRED HAEMOLYTIC ANAEMIA

IMMUNE HAEMOLYTIC ANAEMIA

These can be subdivided into:a) Autoimmuneb) Alloimmunec) Drug-induced

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:

Warm AIHA:

Antibody usually IgG, but may be IgM or IgA CAUSES –1. alternation in membrane surface antigen2. 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

Incidence:

Occurs in either sex but female preponderance reported

Occurs in all ages

Higher incidence noted in patients > 45 years

Clinical Features:

Hemolytic anaemia of varying severity Tends to remit and relapse Haemoglobinurea rare Jaundice Splenomegaly

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 

Serological Features

Direct antiglobulin test (DAT; Coomb's test) usually positive

Indirect antiglobulin test positive RBC may be coated with

1) IgG alone2) IgG and complement3) complement only Rarely anti-IgA and anti-IgM encountered

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

 

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)

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

Pathogenesis:

Specificity usually against I/i antigens

Bind red cells in peripheral circulation impeding capillary flow, producing acrocyanosis

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

Laboratory Features:

Anaemia- mild to moderate Blood film:a) agglutination, or rouleaxb) spherocytosis less marked than warm AIHA

DAT +ve: complement only Anti-I: idiopathic disease, mycoplasma,

some lymphomas Anti-i: infectious mononucleosis,

lymphomas

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

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

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

Non-immune haemolytic anaemias:

Paroxysmal nocturnal haemoglobinuria (PNH)

Red cell fragmentation syndromes March haemoglobinuria Infections Chemical and physical agents Secondary haemolytic anaemia

Paroxysmal nocturnal haemoglobinuria (PNH)

Acquired haemopoietic stem cell disorder Characterized by increased sensitivity of red cells to

haemolysis by complement

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

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

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

Treatment:

Transfusion Oral iron Folate supplements Steroids may be of benefit Anticoagulation for thrombotic

complications

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

Laboratory Findings:

Blood film:1) schistocytes prominent,2) spherocytes, 3) reticulocytes,4) normoblasts Thrombocytopenia Coagulopathy in DIC

Traumatic cardiac haemolytic anaemia

Seen in patients with1) prosthetic heart valves, 2) cardiac valvular disorders esp. severe aortic

stenosis Due to1) physical damage of red cells from turbulence 2) high shear stresses Anaemia usually mild