Levine M N, Gent M, Hirsh J, Weitz J, Turpie A G, Powers P, Neemeh J, Willan A, Skingley P
Department of Medicine, McMaster University, Hamilton, Ontario.
Arch Intern Med. 1996 Apr 22;156(8):851-6.
Deep vein thrombosis is common in patients undergoing major knee surgery. Static graduated compression stockings effectively prevent venous thrombosis in general surgery. Because of the demonstrated prophylactic efficacy of pneumatic compression in knee surgery, the similar efficacy of static graduated compression and pneumatic compression in neurosurgery, and the easier use of static graduated compression in knee surgery, graduated static compression stockings were used as the control arm in our clinical trial. Although low-molecular-weight heparin had been shown to be effective in general surgery and hip replacement, its efficacy was unproved in knee surgery.
A double-blind, randomized trial compared the combination of low-molecular-weight heparin and graduated compression stockings with graduated compression stockings alone in patients undergoing major knee surgery. Patients received either ardeparin (Normiflo) (low-molecular-weight heparin), 0.005 mL/kg (50 anti-Xa U/Kg), or placebo. Both were administered subcutaneously twice daily commencing 12 to 24 hours after surgery and continued for 14 days or until discharge, if sooner. Both study groups wore graduated compression stockings. Bilateral venography was performed on day 14, or sooner if the patient was ready for discharge.
One hundred twenty-two patients were allocated to receive ardeparin and 124 received placebo. Ninety-six patients in the ardeparin group and 103 in the placebo group had evaluable venograms. Deep vein thrombosis was detected in 28 patients in the ardeparin group and in 60 in the placebo group. Proximal deep vein thrombosis was detected in two patients who received ardeparin and 16 who received placebo. One patient in each group, both of whom did not have venography, experienced pulmonary embolism. Thus, deep vein thrombosis or pulmonary embolism was detected in 29 (29.9%) of the 97 patients in the ardeparin group and in 61 (58.7%) of the 104 patients in the placebo group, a relative risk reduction of 49% (P < 00.1). The rate of major bleeding in the ardeparin group was 2.5%, compared with 2.4% in the placebo group.
Ardeparin administered postoperatively twice daily is effective and safe for the prevention of venous thrombosis in patients undergoing major knee surgery. Whereas graduated compression stockings have been shown to be effective prophylactic agents in general surgery and neurosurgery, they have little effect in knee surgery.
深静脉血栓形成在接受大型膝关节手术的患者中很常见。静态分级压力袜在普通外科手术中能有效预防静脉血栓形成。由于充气加压在膝关节手术中已证实具有预防效果，在神经外科手术中静态分级压力与充气加压具有相似效果，且在膝关节手术中静态分级压力使用起来更便捷，因此在我们的临床试验中静态分级压力袜被用作对照组。尽管低分子量肝素在普通外科手术和髋关节置换手术中已显示出有效性，但其在膝关节手术中的效果尚未得到证实。
一项双盲随机试验比较了低分子量肝素与分级压力袜联合使用和单独使用分级压力袜对接受大型膝关节手术患者的影响。患者分别接受阿地肝素（诺美孚）（低分子量肝素），剂量为0.005 mL/kg（50抗Xa单位/千克），或安慰剂。两者均在术后12至24小时开始每天皮下注射两次，持续14天，或直至出院（若出院更早则提前结束）。两个研究组均穿着分级压力袜。在第14天进行双侧静脉造影，若患者准备出院则可提前进行。
122例患者被分配接受阿地肝素治疗，124例接受安慰剂治疗。阿地肝素组96例患者和安慰剂组103例患者有可评估的静脉造影结果。阿地肝素组28例患者和安慰剂组60例患者检测到深静脉血栓形成。接受阿地肝素治疗的2例患者和接受安慰剂治疗的16例患者检测到近端深静脉血栓形成。每组各有1例未进行静脉造影的患者发生肺栓塞。因此，阿地肝素组97例患者中有29例（29.9%）检测到深静脉血栓形成或肺栓塞，安慰剂组104例患者中有61例（58.7%）检测到，相对风险降低49%（P<0.01）。阿地肝素组严重出血发生率为2.5%，安慰剂组为2.4%。
术后每天两次使用阿地肝素对接受大型膝关节手术的患者预防静脉血栓形成有效且安全。虽然分级压力袜在普通外科手术和神经外科手术中已被证明是有效的预防药物，但在膝关节手术中效果甚微。
