Heparin-induced thrombocytopenia: pathophysiology and new treatment options

Heparin induced thrombocytopenia (HIT) is a severe complication of heparin therapy. It is generally accompanied by a paradoxical decrease in platelets leading to activation of platelets and of the coagulation system. HIT type I is a mild, transient, non-immune disorder. HIT type II is an immune-mediated reaction towards neo-antigen on PF4, which is platelet factor 4 (PF4) that is exposed upon binding to heparins. A low sulfated octasaccharide is required for binding to PF4. The generated immunoglobulines bridge platelets by binding to the FcgRIIa-receptor. In patients with HIT type II heparin/LMW-heparin has to be discontinued immediately upon clinical suspicion. Diagnosis can be confirmed by laboratory tests. As patients are at high risk for or because they have developed thromboembolism, anticoagulation is mandatory, despite thrombocytopenia. Treatment options are danaparoid, r-hirudin, bivalirudin, argatroban, dextransulfate, and dermatansulfate. In future, fondaparinux and ximelagatran may be considered for treatment.