Farner B, Eichler P, Kroll H, Greinacher A
Institute for Immunology and Transfusion Medicine, Ernst-Moritz-Arndt-University, Greifswald, Germany.
Thromb Haemost. 2001 Jun;85(6):950-7.
Heparin-induced thrombocytopenia (HIT) is a hypercoagulable syndrome strongly associated with thrombosis that is usually treated with drugs that inhibit factor Xa (danaparoid) or thrombin (lepirudin). In the present study the outcome of HIT-patients treated with danaparoid or lepirudin was compared using the single or combined endpoints of new thromboembolic complications (new TECs), amputations and/or death, and major bleeding. HIT-patients treated with lepirudin were enrolled in two prospective trials and patients, who were identified in the same two laboratories during the same time period, who were not enrolled into these studies but treated with danaparoid, were assessed retrospectively according to a standardized questionnaire. 126 danaparoid (60.3% female) and 175 lepirudin treated patients (58.3% female) fulfilled the same inclusion and exclusion criteria. In a time-to-event-analysis the cumulative risk of combined endpoint was higher in HIT-patients without thromboembolic complication at baseline treated with danaparoid (usually in prophylactic dose 750 anti-factor Xa units b.i.d. or t.i.d.s.c.) as compared to lepirudin (aPTT adjusted) (P = 0.020). Whereas HIT-patients with TEC at baseline who were usually treated with therapeutic dose had a similar outcome in both treatment groups (P = 0.913). Major bleeding occurred in 2.5% (95% CI 0.5-7.0%) of danaparoid treated patients as compared to 10.4% (95% CI 6.3-15.9%) of lepirudin treated patients until day 42 (P = 0.009). This indicates that the efficacies of therapeutic doses of danaparoid or lepirudin in preventing death, amputation or new TEC in HIT-patients do not differ largely, but the risk of bleeding seems to be higher in lepirudin treated patients. The prophylactic dose of danaparoid approved in the European Union for HIT without TEC at baseline seems suboptimal. A prospective comparative trial is required to verify these preliminary conclusions.
肝素诱导的血小板减少症（HIT）是一种与血栓形成密切相关的高凝综合征，通常用抑制Xa因子的药物（达那肝素）或凝血酶的药物（比伐卢定）进行治疗。在本研究中，使用新的血栓栓塞并发症（新TECs）、截肢和/或死亡以及大出血的单一或联合终点，比较了接受达那肝素或比伐卢定治疗的HIT患者的结局。接受比伐卢定治疗的HIT患者参加了两项前瞻性试验，在同一时间段内于同一两个实验室被确诊但未参加这些研究而接受达那肝素治疗的患者，根据标准化问卷进行回顾性评估。126例接受达那肝素治疗的患者（60.3%为女性）和175例接受比伐卢定治疗的患者（58.3%为女性）符合相同的纳入和排除标准。在一项事件发生时间分析中，与接受比伐卢定（活化部分凝血活酶时间[aPTT]调整）治疗的患者相比，基线时无血栓栓塞并发症的接受达那肝素治疗的HIT患者（通常采用预防性剂量750抗Xa因子单位，每日两次或三次皮下注射）联合终点的累积风险更高（P = 0.020）。而基线时有TEC的HIT患者通常接受治疗性剂量，两个治疗组的结局相似（P = 0.913）。直至第42天，接受达那肝素治疗的患者中有2.5%（95%置信区间0.5 - 7.0%）发生大出血，而接受比伐卢定治疗的患者中有10.4%（95%置信区间6.3 - 15.9%）发生大出血（P = 0.009）。这表明治疗剂量的达那肝素或比伐卢定在预防HIT患者死亡、截肢或新TEC方面的疗效差异不大，但接受比伐卢定治疗的患者出血风险似乎更高。欧盟批准的用于基线时无TEC的HIT患者的达那肝素预防性剂量似乎并不理想。需要进行一项前瞻性比较试验来验证这些初步结论。
