Although there have been several RCTs evaluating the efficacy of LMWH for prophylaxis in medical patients, published descriptions of secondary safety endpoints such as HIT are usually brief and often inadequate to judge whether the occurrences of thrombocytopenia were due to HIT or not (Samama et al., 1999; Turpie, 2000; Leizorovicz et al., 2004). In one RCT of prophylactic-dose LMWH (enoxaparin) versus UFH in medical patients, no cases of new onset of thrombocy-topenia (platelet count <100 x 109/L) were observed in 216 patients randomized to receive LMWH (Bergmann and Neuhart, 1996). In another RCT that compared deep-vein thrombosis treatment with LMWH (reviparin) versus UFH, none of 720 patients who received LMWH developed (antibody-positive) HIT, whereas one of 356 (0.3%) patients treated with UFH manifest this complication (Lindhoff-Last et al., 2002). Interestingly, if the definition of HIT in that study was expanded to include thrombosis and a positive test for anti-PF4/heparin antibodies (even without thrombocytopenia), then a greater event-rate was observed in the UFH-treated patients (2.2% vs. 0.1%; p = 0.00087) (Warkentin and Greinacher, 2005). This RCT also showed a greater frequency of antibody formation in the UFH-treated arm (21.1% vs. 6.2%; p < 0.0001).
In a prospective cohort study specifically designed to ascertain the incidence of HIT in medical patients receiving LMWH, 14/1754 (0.8%) developed HIT
(Prandoni et al., 2005), a frequency similar to that reported by the same investigators in medical patients receiving UFH (Girolami et al., 2003). In contrast, the retrospective study of VTE prophylaxis by Creekmore and colleagues (2006) observed a significantly lower frequency of HIT in medical patients receiving LMWH (1/1189 = 0.08%) compared with the same patient population receiving UFH (43/8420 = 0.5%; p = 0.037). Similarly, in "before-after" prospective cohort studies performed in neurologic patients, the frequency of HIT tended to be lower in patients treated with LMWH (nadroparin) compared with UFH (0% vs. 2.5%; p = 0.17), with a significantly lower frequency of heparin-dependent antibody formation among the patients receiving LMWH (1.8% vs. 10.5%; p < 0.001 ) (Harbrecht et al., 2004; Pohl et al., 2005).
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