Two large prospective studies suggest that HIT is an important problem in orthopedic patients receiving UFH (Warkentin et al., 1995, 2003, 2005a; Greinacher et al., 2005a). When using a proportional fall in platelet count (e.g., 50% or greater) that began on or after day 5 of heparin treatment, and that was confirmed by serologic testing for HIT antibodies, both studies observed a frequency of HIT of about 5% (Table 3). Each study used porcine mucosal heparin, derived from a different manufacturer, given by the subcutaneous (sc) route at a dosage of 15,000 U/day. Other studies of postorthopedic UFH thromboprophylaxis (using confirmatory in vitro testing) have shown frequencies of HIT of about 2.0% (Leyvraz et al., 1991; Mahlfeld et al., 2002).
There is little prospective information of the frequency of HIT in other postoperative surgical populations treated with UFH (Table 3). Three studies have been performed on postoperative cardiac surgical patients who also received postoperative UFH in addition to high doses of UFH during preceding cardiopulmon-ary bypass (CPB) (Trossaert et al., 1998; Warkentin et al., 2000; Pouplard et al., 1999) (Table 3). Pooling the three studies, about 2.4% of the patients developed serologically confirmed HIT. Interestingly, the frequency of HIT in this population appears to be lower than in orthopedic patients receiving UFH, even though the cardiac surgical patients appear to have a higher frequency of formation of HIT antibodies (Warkentin et al., 2000).
Isolated limb perfusion (ILP) with melphalan employs extracorporeal circulation (and thus high-dose UFH) to treat melanoma or unresectable sarcoma limited to an extremity. In one study, HIT occurred in three of 108 patients (2.8%), who also received sc UFH prophylaxis following ILP (Masucci et al., 1999). The occurrence of arterial thrombosis and partial limb amputation in two of these patients with HIT led the investigators to discontinue routine UFH prophylaxis post-ILP. The hypothesis that ILP is a high-risk situation for HIT was supported by a follow-up prospective study by these same investigators showing that heparin-dependent antibodies were formed in all nine patients who underwent ILP (despite not receiving postoperative UFH prophylaxis), with eight having "strong" antibodies that effected serotonin release in vitro (Masucci et al., 1999).
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