Pathophysiology of heparin-induced thrombocytopenia clinical and diagnostic implications - A review

Objective.-This review of heparin-induced thrombocytopenia (HIT), the most frequent and dangerous side effect of heparin exposure, covers the epidemio logy, pathophysiology, clinical presentation, diagnosis, and treatment of t his disease syndrome. Data Sources and Study Selection.-Current consensus of opinion is given bas ed on literature reports, as well as new information where available. A com prehensive analysis of the reasons for discrepancies in incidence numbers i s given. The currently known mechanism is that HIT is mediated by an antibo dy to the complex of heparin-platelet factor 4, which binds to the Fc recep tor on platelets. New evidence suggests a functional heterogeneity in the a nti-heparin-platelet factor 4 antibodies generated to heparin, and a "super active" heparin-platelet factor 4 antibody that does not require the presen ce of heparin to promote platelet activation or aggregation has been identi fied. Up-regulation of cell adhesion molecules and inflammatory markers, as well as preactivation of platelets/endothelial cells/leukocytes, are also considered to be related to the pathophysiology of HIT. Issues related to t he specificity of currently available and new laboratory assays that suppor t a clinical diagnosis are addressed in relation to the serotonin-release a ssay. Past experience with various anticoagulant treatments is reviewed wit h a focus on the recent successes of thrombin inhibitors and platelet GPIIb /IIIa inhibitors to combat the platelet activation and severe thrombotic ep isodes associated with HIT. Conclusions.-The pathophysiology of HIT is multifactorial. However, the pri mary factor in the mediation of the cellular activation is due to the gener ation of an antibody to the heparin-platelet factor 4 complex. This review is written as a reference for HIT research.