Frequency of HIT in Medical Patients Treated with Porcine Mucosal UFH

Table 2 also lists the frequency of HIT observed in several prospective studies that have evaluated medical patients receiving intravenous, therapeutic-dose porcine UFH, usually for venous thromboembolism (VTE), myocardial infarction and acute coronary syndromes (MI/ACS), or hemodialysis (HD). Excluding studies of HD, an overall frequency of HIT of slightly less than 1% is suggested. This is a relatively low number, particularly when one considers that, paradoxically, the frequency appears to be much higher in postoperative surgical patients who received lower (prophylactic) doses of porcine heparin (discussed subsequently).

In contrast, HIT may occur more often in prospective studies of acute HD patients receiving porcine UFH (Yamamoto et al., 1996). Whether this is a real difference that reflects increased platelet activation (and PF4 release) during HD or it reflects a more sensitive definition of thrombocytopenia (any platelet count fall associated with line clotting) is unknown. The frequency of clinical HIT in chronic HD patients appears to be less than 2% and may be considerably lower, but up to 18% develop a positive EIA for anti-PF4/heparin antibodies. Whether the incidence of elevated levels of anti-PF4/heparin antibodies and clinical HIT are dependent on the time since the initiation of HD is unclear. Some have suggested that the frequency of anti-PF4/heparin antibody increases with time (Palomo et al., 2005), while others have found no association (Peña de la Vega et al., 2005). Two studies suggest that the antibodies tend to develop early after initiation of HD, and may disappear after months, despite ongoing heparin exposure (Nakamoto et al., 2005; Skouri et al., 2006). Most studies have not found an association between vascular access thrombosis and elevated levels of anti-PF4/heparin antibodies (Greinacher et al., 1996; Sitter et al., 1998; O'Shea et al., 2002; Palomo et al., 2005; Peña de la Vega et al., 2005; Carrier et al., 2007).

The incidence of HIT in medical patients receiving prophylactic-dose UFH remains poorly defined but also appears to be lower than that observed in surgical patients receiving UFH prophylaxis. Girolami et al. (2003) prospectively evaluated 598 hospitalized medical patients who received prophylactic (n = 360) and therapeutic (n = 238) dose UFH. Overall, five patients developed HIT, all of whom were receiving UFH in prophylactic doses (0.8% of combined group, or 1.4% of patients receiving prophylactic-dose UFH). In an RCT comparing low-dose LMWH with UFH for VTE prevention, HIT was believed to have occurred in 1/223 (0.4%) of UFH-treated patients, based on the timing of the platelet count fall (serology was not performed) (Bergmann and Neuhart, 1996). In a retrospective analysis, Creekmore et al. (2006) reported a similar incidence of 0.5% (43/8420) in medical patients receiving UFH.

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