ABSTRACT
Immune (type II) heparin-induced thrombocytopenia (HIT) remains a major iatrogenic complication of heparin therapy. It is triggered by “heparin-dependent” antibodies targeted to protein-heparin-mainly platelet factor 4 (PF4)—complexes. Its frequency could still be underestimated (Francis, 2005). HIT develops more frequently during therapy with unfractionated heparin (UFH) (Poncz, 2005; Greinacher, 2006), especially in the setting of vascular alteration, blood activation, and inflammation. PF4 complexed to heparin (PF4-H) was identified as the major target antigen for heparin-dependent antibodies involved in the pathogenesis of immune HIT 15 yr ago (Amiral et al., 1992, 1995) and confirmed by various investigators (Gruel et al., 1993; Greinacher et al., 1994, 1995; Kelton et al., 1994; Visentin et al., 1994). However, today, presence of anti-PF4-H antibodies (especially when they are detected using assays that recognize all three major immunoglobulin classes, IgG, IgA, and IgM) must be understood to be just a risk factor for HIT rather than an absolute indicator of this clinical complication (see Chapter 10). Conversely, when thrombocytopenia (and/or thrombosis) develops 5 or more days after beginning heparin therapy, the presence of these anti-PF4-H antibodies-especially when they are of IgG class and found at high levels-essentially confirms the diagnosis of HIT (Lindhoff-Last et al., 2001; Warkentin, 2004, 2005; Warkentin and Sheppard, 2006; Warkentin et al., 2005; Greinacher, 2006).
