ABSTRACT
About 10 years ago, platelet factor 4 (PF4) complexed to heparin (PF4-H) was identified as the major target antigen for heparin-dependent antibodies involved in the pathogenesis of immune heparin-induced thrombocytopenia (HIT) (Amiral et aI., 1992, 1995; Gruel et aI., 1993; Greinacher et aI., 1994, 1995; Kelton et aI., 1994; Visentin et aI., 1994). Occasionally, other antigens can be involved, such as interleukin-8 (IL-8) or neutrophil-activating peptide2 (NAP-2), two CXC chemokines of the PF4 superfamily (Amiral et aI., 1996a). There is now increasing evidence that the risk ofHIT depends on the type of heparin used, its sulfation grade, the therapy duration, and the patient's clinical context (Kelton, 1992; Warkentin and Kelton, 1996) (see Chap. 4). However, many questions remain unresolved: How are antibodies generated? Why are they observed in only a subgroup of patients receiving heparin? How do they become pathogenic in only a few of the latter? Indeed, antibodies to PF4-H develop surprisingly often in many heparin-treated patients, especially in the context of platelet activation (e.g., heart surgery using cardiopulmonary bypass) (Amiral et aI., 1996b; Visentin et aI., 1996).
