Albada J, Nieuwenhuis H K, Sixma J J
Department of Haematology, University Hospital, Utrecht, The Netherlands.
Circulation. 1989 Oct;80(4):935-40. doi: 10.1161/01.cir.80.4.935.
We performed a prospective, randomized, double-blind trial in 194 unselected patients to determine the safety and efficacy of low molecular weight heparin (Fragmin) compared with standard heparin as the initial treatment of acute venous thromboembolism. Ninety-eight patients received continuous intravenous heparin, and 96 patients received Fragmin for 5-10 days. Doses were adjusted to maintain anti-Xa levels between 0.3 and 0.6 unit/ml for patients with a high risk for a bleeding complication and between 0.4 and 0.9 unit/ml for patients with a low risk for bleeding. Treatment was stopped when a therapeutic level of anticoagulation (International Normalized Ratio greater than 3.5) was reached with coumarins. Thirteen patients in the heparin group and 10 patients in the Fragmin group had a major bleeding complication. The incidence of major and minor bleeding complications combined decreased from 48.9% to 38.5% (95% confidence interval for the difference, -3.5% to +24.2%), corresponding with a relative bleeding risk reduction of 21.2%. There were no significant differences in efficacy as defined by new high-probability defects on repeat ventilation-perfusion scintigraphy of the lung in 80 patients: six of 46 patients in the heparin group and 3 of 34 patients in the Fragmin group had new defects (95% confidence interval for the difference, -9.4% to +17.8%). We conclude that low molecular weight heparin (Fragmin) given in adjusted, continuous, and intravenous doses is safe and effective as initial treatment of acute venous thromboembolism compared with heparin. There is a trend in risk reduction for bleeding in favor of low molecular weight heparin, a trend, however, that is smaller than expected compared with animal studies.
我们对194例未经筛选的患者进行了一项前瞻性、随机、双盲试验，以确定低分子量肝素（法安明）与标准肝素相比，作为急性静脉血栓栓塞初始治疗的安全性和有效性。98例患者接受持续静脉注射肝素，96例患者接受法安明治疗5至10天。对于有出血并发症高风险的患者，调整剂量以维持抗Xa水平在0.3至0.6单位/毫升之间；对于出血风险低的患者，维持在0.4至0.9单位/毫升之间。当使用香豆素达到治疗性抗凝水平（国际标准化比值大于3.5）时停止治疗。肝素组有13例患者、法安明组有10例患者发生了严重出血并发症。严重和轻微出血并发症的合并发生率从48.9%降至38.5%（差异的95%置信区间为-3.5%至+24.2%），相对出血风险降低了21.2%。在80例患者中，根据重复肺通气灌注闪烁扫描新出现的高概率缺损所定义的疗效方面，两组无显著差异：肝素组46例患者中有6例、法安明组34例患者中有3例出现新缺损（差异的95%置信区间为-9.4%至+17.8%）。我们得出结论，与肝素相比，调整剂量后持续静脉注射低分子量肝素（法安明）作为急性静脉血栓栓塞的初始治疗是安全有效的。在降低出血风险方面，有倾向于低分子量肝素的趋势，然而，与动物研究相比，这一趋势小于预期。
