Summary.  Objectives: To assess efficacy and safety of lepirudin in patients with heparin‐induced thrombocytopenia (HIT) in a prospective study (HAT‐3) as well as in a combined analysis of all HAT study data. Patients/methods: Patients with laboratory‐confirmed HIT were treated with lepirudin in three different aPTT‐adjusted dose regimen and during cardiopulmonary bypass (CPB). Endpoints were new thromboembolic complications (TEC), limb amputations, and death and major bleeding. A historical control group (n = 120) was used for comparison. Results: After start of lepirudin in 205 patients treated in HAT‐3, the combined endpoint occurred in 43 (21.0%). Thirty (14.6%) patients died, 10 (4.9%) underwent limb amputation, and 11 (5.4%) new TECs occurred. Major bleeding occurred in 40 patients (19.5%) (seven during CPB surgery). Combining all prospective HAT trials (n = 403), after start of lepirudin treatment, the combined endpoint occurred in 82 patients (20.3%), with 47 deaths (11.7%), 22 limb amputations (5.5%), 30 new TECs (7.4%), and 71 (17.6%) major bleedings. Compared with the historical control group (log‐rank test), the combined endpoint after start of treatment was reduced (29.7% vs. 52.1%, P = 0.0473), primarily because of reduction in new thromboses (11.9% vs. 32.1%, P = 0.0008). Mean lepirudin maintenance doses ranged from 0.07 to 0.11 mg kg−1 h−1. Major bleeding was more frequent in the lepirudin‐treated patients (29.4% vs. 9.1%, P = 0.0148). Conclusions: The rate of new TECs in HIT patients is low after start of lepirudin treatment. The rate of major bleeding of 17.6% might be reduced by reducing the starting dose to 0.1 mg kg−1 h−1.

Heparin can induce heparin-induced thrombocytopenia (HIT). The combined effect of type of surgery (major vs minor) and heparin on this prothrombotic immune reaction to platelet factor 4 (PF4)/ heparin was analyzed. In a randomized, double-blind study, trauma patients receiving low-molecular-weight (LMWH) or unfractionated heparin (UFH) for thrombosis prophylaxis were assessed for PF4/ heparin-antibody seroconversion, HIT, and thrombosis according to type of surgery. The risk for seroconversion was higher than major versus minor surgery odds ratio, 7.98 [95% confidence interval, 2.06-31.00], P ‫؍‬ .003, controlled for potential confounders, as was the risk for HIT (2.2% [95% confidence interval, 0.3%-4.1%] vs 0.0%, P ‫؍‬ .010). During LMWH compared with UFH thromboprophylaxis, HIT (1 of 298 vs 4 of 316; P ‫؍‬ .370) and PF4/heparin seroconversion (1.7% vs 6.6%; P ‫؍‬ .002) were less frequent, driven by differences in patients undergoing major surgery (incidence of HIT: LMWH 0.8% vs UFH 4.0%; P ‫؍‬ .180; seroconversion rates: 4.0% vs 17.0%; P ‫؍‬ .001). After minor surgery, no case of HIT occurred. The severity of trauma and the need for major surgery strongly influence the risk of an anti-PF4/heparin immune response, which is then increased by UFH. In major trauma certoparin may be safer than UFH because it induces HIT-antibody seroconversion, and the corresponding risk of HIT, less frequently. (Blood.

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References

patients requiring prolonged intensive care unit treatment after cardiopulmonary bypass. J Thromb Haemost 2008; 6: 428-35.Summary. Background: The diagnosis of heparin-induced thrombocytopenia (HIT) is problematic in postcardiac surgery (CS) intensive care unit (ICU) patients, as there are multiple potential explanations for thrombocytopenia and the presence of anti-platelet factor 4/heparin antibodies is not highly specific for HIT. Two platelet count profiles for HIT -a 40% or greater fall in platelet count beginning on or after day 5 (pattern 1) and persisting thrombocytopenia (< 100 · 10 9 L -1 ) beyond day 7 (pattern 2) -have been described in post-CS patients. Methods and results: We examined the platelet count profiles of 329 consecutive post-CS patients who required ICU treatment beyond 7 days. Although 70 patients (21.3%) developed thrombocytopenia (57.1% pattern 1, 42.9% pattern 2), the overall incidence of HIT was only 1.8% [6/329; 95% confidence interval (95% CI) 0.7-3.9%] in these ICU patients, with more HIT patients showing a pattern 2 than a pattern 1 platelet count decrease (four vs. two patients). Notably, pattern 2 patients with HIT also showed a new proportional fall of > 30% in platelet count between postoperative days 5 and 10. Among the remaining 2242 post-CS patients without a prolonged ICU stay, only three (0.1%; 95% CI 0.03-0.4%) developed symptomatic HIT (OR 0.07; 95% CI 0.01-0.3; P = 0.0002 vs. ICU patients), all presenting with pattern 1. Conclusions: Among post-CS ICU patients, a postoperative platelet count fall between days 5 and 10 increases diagnostic specificity for HIT, irrespective of whether this platelet count fall occurs after postoperative platelet count recovery (pattern 1) or is superimposed upon persisting postoperative thrombocytopenia (pattern 2). A prospective study is required in order to validate the findings of this retrospective analysis.