Immunobiology and Pathophysiology of Heparin-Induced Thrombocytopenia/ Thrombosis Syndrome-An Update

Heparin-induced thrombocytopenia (HIT) syndrome is one of the more frequent and dangerous autoimmune complications of heparin therapy in clinical setting. It is now widely accepted that heparins are capable of complexing with endogenous chemokines and modify at molecular level to trigger the HIT-associated antibodies responsible for pathogenesis. Newer evidence suggests a functional heterogeneity in the HIT antibodies. Besides platelet factor IV (PF IV), there are several endogenous factors, which are responsible for the upregulation of HIT antibodies in various prophylactic and therapeutic regimens. While the pathophysiology and the mechanisms of action in HIT are rather complex, the role of IgG subtype antibodies is clearly established in mediating the pathogenesis. Currently available antithrombin drugs seem to be promising therapeutic modalities to combat the severe thrombotic episode and platelet activation associated with HIT. The clinical relevance of the pathologically nonfunctional HIT antibodies and the mechanism(s) of their formation, in terms of both correlative evidence and causal relationships, need further investigation.