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5 6 7 8 9 10 11 12 >13 Onset of HIT (days after starting heparin)

FIGURE 1 (Continued from previous page.) HIT in a clinical trial of postoperative orthopedic patients. (A) Serial platelet counts of nine patients with HIT (platelet count nadir <150x 109/L). The bold line and shaded area indicate the mean (±2 SD) platelet count in the reference population (367 patients who tested negative for HIT antibodies). The reference population indicates the occurrence of postoperative thrombocytopenia (days 1-3), followed by postoperative thrombocytosis (maximal, days 11-14). Nine patients developed serologically confirmed HIT, with a platelet count fall to <150 x 109/L; eight of the nine patients developed HIT-associated thrombosis (see insert for description of the types of thrombi observed; all thrombi were venous, except for a mesenteric artery thrombosis). (B) Serial platelet counts of nine patients with HIT (platelet nadir >150 x 109/L, but platelet count fall >50%). Five patients developed DVT. (For one of the patients, the platelet count began to fall on day 5 after UFH "flushes" were received through an intra-arterial catheter placed at the time of surgery.) HIT developed in seven patients receiving UFH and two receiving LMWH (The platelet count fell abruptly on day 12 (postoperative day 13), together with symptoms and signs of an acute systemic reaction, following administration of a 5000 U intravenous UFH bolus. However, the first clinical manifestation of HIT was on day 9 (erythematous skin lesions at heparin injection sites). The platelet count fell abruptly on postoperative day 13 when 5000 U of intravenous UFH was given. (C) Day of onset of HIT for 18 patients observed in a clinical trial. HIT began between days 5 and 10, inclusive, in all 18 patients. Length of heparin treatment was variable; thus, the remaining number of patients at risk for HIT for each day of follow-up is shown (n). The platelet count fell abruptly on day 10 after administration of a 5000 U intravenous UFH bolus, followed by therapeutic-dose UFH infusion. However, positive HIT antibodies were first detected by platelet factor 4-heparin-enzyme-immunoassay on day 6 of treatment with subcutaneous UFH, 7500 U twice daily. Abbreviations: DVT, deep vein thrombosis; HIT, heparin-induced thrombocytopenia; LMWH, low molecular weight heparin; UFH, unfractio-nated heparin. Source: (A, C) from Warkentin et al., 1995, and Warkentin, 2000; (B) from Warkentin et al., 1995, 2003.

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