Immune-Mediated Cell Destruction

Alloimmune

    Antibodies directed against:
  • Antigen from the same species
       .Blood Transfusion in which RBCs not entirely compatible to our own (Haemolytic Transfusion Reaction)
       .Routinely match only the MAJOR antigen types (eg ABO, Rh)
  • Foreign antigens such as those which differ between mother and child during pregnancy    .Foeto-maternal haemorrhage
       .Antibodies may cross the placenta during a subsequent pregnancy (Haemolytic Disease of the Newborn (HDN))
Autoimmune
  • Classified according to the thermal reactivity of the antibody
  • Individual may or may not be anaemic depending on the bone marrow's ability to compensate

  • Warm Autoimmune Haemolytic Anaemia (AIHA)

    • 50% spontaneous/idiopathic
    • 50% due to secondary disorders including:
      • Systemic lupus erythematosus and other autoimmunities
      • Chronic lymphocytic leukaemia
      • Hodgkin's disease
      • Viral infections
      • Neoplastic disorders
      • Chronic inflammatory diseases
    • Usually IgG (IgA and IgM are rare) class Ab
    • Lysis occurs through opsonisation of cells by immunoglobulin or the C3b component of complement at 20'C-37'C

    • Symptoms

      • Feeling unwell
      • Symptoms of anaemia, mild jaundice
      • Extravascular blood loss (microspherocytes, polychromasia and NRBC's if severe) usually in the spleen with some liver involvement
      • Can be life-threatening especially if superimposed on some other disease
      • Distinguished from hereditary spherocytosis by family studies and a direct anti-human globulin test (AIHA (+), HS (-))

    • Treatment

      • Steroids to depress Ab production and/or block macrophage Fc receptors
      • High levels of lysis may require splenectomy. The site of haemolysis can be tracked using Cr51-Haemoglobin.
      • Transfusions may also be acted upon by the Ab

    Cold-Reactive Haemolytic Anaemia

    • Generally occurs in the recovery stage after disease
    • Primary disease is often referred to as CHAD (Cold Haemagglutinin Disease) - usually seen with age
    • Can occur secondarily to Mycoplasma pneumonia, viral infections or lymphoproliferative disorders
    • When the periphery of the body (fingers, toes) cools (4'C-32'C), agglutination of the blood occurs that can block the circulation (Raynaud's phenomenon)
    • Mostly IgM class antibodies that bind to the cell, activating the complement cascade, detaching as the temperature rises, leaving complement coated cells to be removed by hepatic macrophages
    • Try to live in a warmer climate
    • Mostly the liver is the site of haemolysis, rarely intravascular
    • MCV, MCH and MCHC are all increased

    Paroxysmal Nocturnal Haemoglobinuria

    • May be found following viral infections
    • In the cold (4'C-20'C), binds IgG class Ab which binds early complement (C') components which become reactive when warm causing lysis. This Ab is called a biphasic Ab
    • Haemoglobinuria, intravascular haemolysis
    • Donath Lansteiner Test (DLT)    Sample of patient blood, on ice, is heated to 37'C. If the Ab is present, intense haemolysis will occur as it warms.
Drug Induced Haemolytic Anaemia
  • Considered benign because the 'cure" involves withdrawl of the offending drug and supportive treatment
  • Immune complex formation-innocent bystander type
    • Can occur when a drug (eg quinine) forms a complex with plasma protein(s) which may elicit a humoral response.
    • HA will develop if this drug-protein complex is adsorbed to the RBC, stimulating a complement cascade
  • Nonspecific adherence-autoantibody inductions
    • Can occur when a drug is non-specifically adsorbed to the RBC, creating a new antigenic complex in combination with the RBC's membrane
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