Heparin-Induced Thrombocytopenia (HIT) Complications and Management

Drug-Induced Thrombocytopenia

• Heparin-induced thrombocytopenia is a complication of heparin therapy
• Thrombosis occurs in 20-50% of patients, continuing for days to weeks after heparin discontinuation
• Heparin-induced skin necrosis and venous gangrene of the limbs can also occur
• Management involves removing the offending drug and using alternative anticoagulants (e.g. direct thrombin inhibitors like lepirudin, argatroban, bivalirudin)

Drug-Induced Haemolytic Anemia

• Premature RBC destruction (hemolysis) can be caused by a defective RBC or abnormal changes in the intravascular environment
• Symptoms include fatigue, malaise, pallor, and shortness of breath
• Intravascular hemolysis is mostly due to hereditary or genetic RBC defects, while extravascular hemolysis is usually immune-mediated
• Extravascular hemolysis is an exaggeration of the normal mechanism of RBC removal, leading to jaundice

Drug-Induced Immune Haemolytic Anemia

• Immunoglobulins (IgG and/or IgM) bind to antigens on the surface of RBCs, initiating destruction through the complement and mononuclear phagocytic systems
• Examples of drug-induced immune haemolytic anemia include:
  • High dose penicillin or cephalosporin (hapten-type reaction)
  • Quinidine, sulfonamides (innocent bystander mechanism)
  • Methyldopa, levodopa, mefenamic acid, diclofenac (autoimmune mechanism)
• Diagnosis involves a Coombs test (Antiglobulin Test)

High-Affinity Hapten-Type Reaction

• Penicillin or metabolite covalently binds strongly to RBC membrane in a dose-related fashion
• Dose-related fashion: > 10 million/day or > 10MU/day or with high penicillin blood level can develop hemolytic anemia
• Complement is not activated, and anemia gradually develops 7-10 days after starting penicillin and reverses after stopping the drug
• Direct Coombs test remains positive for several weeks

Low Affinity Binding Hemolytic Anemia

• Quinidine: binding of drugs or metabolites to circulating serum protein to form a complete antigen
• RBC is lysed, and the immune complex dissociates and repeats the process on a second RBC
• Antibodies are not directed against the RBC but are destroyed as an innocent bystander
• Small doses can cause large-scale hemolysis (intravascular)

Autoimmune Reaction

• Formation of RBC autoantibodies in 10-20% of patients on > 4 months therapy (methyldopa)
• Treatment involves discontinuation of the offending drug, supportive care, and possible RBC transfusion
• Some patients may require azathioprine or cyclophosphamide, or monoclonal antibody therapy

Management of Drug-Induced Immune Haemolytic Anemia

• Removal of the offending agent
• Supportive care (folic acid supplements, glucocorticoids)
• Patients who do not respond may require additional treatment (azathioprine, cyclophosphamide, monoclonal antibody therapy)