ABSTRACT
The most important complication of heparin-induced thrombocytopenia (HIT) is thrombosis. Clinically overt arterial or venous thrombi have been observed in 50% or more patients with HIT in some series (see Chapters 2 and 3), a frequency that far exceeds any other drug-induced immune platelet disorder. The propensity for thrombosis is in part attributable to platelet activation through FcgIIa receptors by IgG-containing complexes comprised of platelet factor 4 (PF4) and heparin (see Chapter 8). Strong support for this concept comes from recent studies involving mice transgenic for human FcgIIA and human PF4 (hPF4) (Reilly et al., 2001; Rauova et al., 2006) (see Chapter 8). However, the “nonpermissive” FcgIIa phenotype affords limited protection against thrombosis (Trikalinos et al., 2001), perhaps because of the high incidence of IgGl antibodies (Denomme et al., 1997). Furthermore, the occasional HIT patient in whom only IgM or IgA antibodies are detected (Amiral et al., 1996; Meyer et al., 2006) suggests that additional factors, acting at the level of the platelet or elsewhere, contribute to the thrombotic diathesis. In addition, thrombosis is usually restricted to large arteries and veins and occurs at a limited number of sites (Greinacher et al., 2005) (see Chapter 2), although HIT antibodies and activated platelets circulate in asymptomatic patients. These considerations point to alterations in the local vascular milieu as influencing the clinical expression of disease.
