Heparin-Induced Thrombocytopenia

occupy FcγIIa receptors, found on the cell surface of platelets, thereby activating the platelets and causing further expression of PF4 in a positive feedback loop mechanism (Figure 1).4 Platelet activation also causes the release of prothrombotic microparticles, platelet consumption, and thrombocytopenia. Activated platelet aggregation and their removal from circulation are believed to be responsible for thrombocytopenia and thrombosis.3,5 The multimolecular antibody complex can also contribute to thrombosis in other ways via interaction with monocytes, producing tissue factor and endothelial injury.6,7 More than 12 million patients and almost one-third of all hospitalized patients receive heparin each year.8 HIT antibodies develop in up to 50% of patients following exposure to heparin and can continue to circulate for three months or more in approximately 40% of patients.9,10 A widespread myth is that a positive result for HIT anti bodies means that a patient has HIT. Actually, heparin–PF4 antibodies are relatively common following heparin exposure and can be nonpathogenic.11 Clinical HIT can lead to a severely prothrombotic state, occurring in 1% to 5% of patients receiving heparin and accounting for 600,000 cases of HIT annually. Half of these patients, (approximately 300,000) experience complications associated with thrombosis, and 90,000 die.3 Generally, the frequency of HIT is dependent on four risk factors:12