HIT antibodies occur commonly in heparin-treated patients. However, as many patients develop neither thrombocytopenia nor thrombosis (Amiral et al., 1996a; Kappers-Klunne et al., 1997; Arepally et al., 1997), it is evident that pathogenicity requires additional factors. Possible factors are number and size of the antigen complexes (Rauova et al., 2005; Greinacher et al., 2006), antibody class (Warkentin et al., 2005b; Juhl et al., 2006), and titer of the HIT antibodies (Suh et al., 1997), as well as optimal concentrations of heparin and PF4 in the blood circulation, which enable the formation of macromolecular PF4-heparin antigen complexes (Horne and Alkins, 1996; Horne and Hutchison, 1998). Thus, during low-dose heparin prophylaxis in a setting of minimal platelet activation, clinical HIT may occur less often than in patients with activated platelets receiving high heparin doses (Fondu, 1995). Accordingly, HIT antibodies are most frequently induced by UFH in patients following cardiopulmonary bypass surgery (~50%), followed by patients undergoing major orthopedic surgery (~15%), and least frequently in medical patients (~3%) (see Chapter 3).
Besides MW, DS and concentration of heparin, additional factors favoring the development of clinical HIT are prethrombotic or inflammatory situations (e.g., open heart surgery) (Visentin et al., 1996), greater susceptibility of the platelets to activation by HIT antibodies (Salem and van der Weyden, 1983), perhaps mediated by increased PF4 binding to platelets (Capitanio et al., 1985), or expression of PF4 (Rauova et al., 2006) and FcyIIa receptors (Chong et al., 1993) on the platelet surface. Further, the polymorphism of the FcyIIa receptor at position Arg-His131 seems to be associated with a predisposition to HIT (Carlsson et al., 1998). Another poorly understood phenomenon is gender imbalance in HIT,
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