Bergqvist D, Burmark U S, Flordal P A, Frisell J, Hallböök T, Hedberg M, Horn A, Kelty E, Kvitting P, Lindhagen A
Department of Surgery, University Hospital, Uppsala, Sweden.
Br J Surg. 1995 Apr;82(4):496-501. doi: 10.1002/bjs.1800820421.
The optimal administration regimens of low molecular weight heparins (LMWHs) have not yet been established. The aim of this study was to compare the efficacy and safety of 2500 and 5000 XaI units of the LMWH dalteparin in patients undergoing elective general surgery for malignant and benign abdominal disease. Prophylaxis was started in the evening before surgery and given once-daily every evening thereafter. The study was designed as a prospective, randomized, double-blind, multicentre trial. Some 66.4 per cent of patients were operated on for a malignant disorder. The primary endpoint was deep vein thrombosis (DVT) detected with the fibrinogen uptake test. Bleeding complications were recorded and classified. Analysis was made both on an intention to treat basis and in patients given correct prophylaxis (86.3 per cent). A total of 2097 patients were randomized and 27 excluded after randomization. A technically correct fibrinogen uptake test was obtained in 1957 patients. The incidence of DVT was significantly lower in patients given 5000 XaI units, this being true for both correct prophylaxis (6.8 versus 13.1 per cent, P < 0.001), on an intention to treat basis (6.6 versus 12.7 per cent, P < 0.001), and in patients with malignant disease (8.5 versus 14.9 per cent, P < 0.001). Sixty-seven patients (3.2 per cent) died within 30 days with no difference between the groups. There were two cases of fatal pulmonary embolism. The frequency of bleeding complications in the whole series was higher in patients randomized to 5000 XaI units (4.7 versus 2.7 per cent, P = 0.02), although this was not the case in those operated on for malignant disease (4.6 versus 3.6 per cent, P not significant). Dalteparin in the dose of 5000 XaI units started in the evening before surgery has a good thromboprophylactic effect in high-risk general surgery at the cost of a small bleeding risk. In patients with malignant disease there was no increased risk of bleeding. The overall frequency of fatal pulmonary embolism with dalteparin is extremely low, even in this high-risk group of patients.
低分子量肝素（LMWHs）的最佳给药方案尚未确定。本研究的目的是比较2500和5000抗Xa国际单位的低分子量肝素达肝素在接受择期普通外科手术治疗恶性和良性腹部疾病患者中的疗效和安全性。预防措施于手术前一晚开始，此后每晚给药一次。该研究设计为一项前瞻性、随机、双盲、多中心试验。约66.4%的患者接受了恶性疾病手术。主要终点是通过纤维蛋白原摄取试验检测到的深静脉血栓形成（DVT）。记录并分类出血并发症。在意向性治疗基础上以及接受正确预防措施的患者（86.3%）中进行分析。共有2097例患者被随机分组，随机分组后27例被排除。1957例患者获得了技术上正确的纤维蛋白原摄取试验结果。接受5000抗Xa国际单位治疗的患者DVT发生率显著较低，在正确预防措施组（6.8%对13.1%，P<0.001）、意向性治疗基础上（6.6%对12.7%，P<0.001）以及恶性疾病患者中均如此（8.5%对14.9%，P<0.001）。67例患者（3.2%）在30天内死亡，两组之间无差异。有2例致命性肺栓塞。随机接受5000抗Xa国际单位治疗的患者在整个系列中出血并发症的发生率较高（4.7%对2.7%，P=0.02），尽管在接受恶性疾病手术的患者中并非如此（4.6%对3.6%，P无统计学意义）。术前一晚开始使用5000抗Xa国际单位剂量的达肝素在高危普通外科手术中有良好的血栓预防作用，但有轻微的出血风险。在恶性疾病患者中，出血风险没有增加。即使在这组高危患者中，达肝素导致致命性肺栓塞的总体发生率也极低。
