Heparin-Induced Thrombocytopenia (HIT) Complications and Management

Study Notes

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)

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

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)

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

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)

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

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)