Low molecular weight versus standard heparin for prevention of venous thromboembolism after major abdominal surgery. The Thromboprophylaxis Collaborative Group

Lancet. 1993 Jan 30;341(8840):259-65. doi: 10.1016/0140-6736(93)92614-y.


Low-molecular-weight heparin (LMWH) is effective in the prevention of postoperative venous thromboembolism but does it have the safety advantages over standard heparin (SH) that have been claimed? In a multicentre randomised trial in 3809 patients undergoing major abdominal surgery (1894 LMWH, 1915 SH) heparin was given preoperatively and continued for at least 5 postoperative days. Patients were assessed in the postoperative period and were followed up for at least 4 weeks, the emphasis being on safety. Major bleeding events occurred in 69 (3.6%) patients in the LMWH group and 91 (4.8%) patients in the SH group (relative risk 0.77, 95% confidence interval 0.56-1.04; p = 0.10). 93 indices of major bleeding were observed in the 69 LMWH patients and 141 in the SH patients. (p = 0.058). Severe bleeding was less frequent in the LMWH group (1.0% vs 1.9%; p = 0.02), as was wound haematoma (1.4% vs 2.7%; p = 0.007). Bleeding episodes with LMWH were less likely to lead to further surgery to evacuate a haematoma or to control bleeding, and injection site bruising was also less common in the LMWH group. No significant differences were found in the efficacy of the two agents. Perioperative death rates were 3.3% in the LMWH group and 2.5% in the SH group; pulmonary emboli were detected in 0.7% and 0.7%; and deep-vein thrombosis was diagnosed in 0.6% of patients in each group. Follow-up was done on 91% of 3699 evaluable patients. There were 19 further deaths (10 LMWH, 9 SH group) and 25 patients with thromboembolic complications (15 and 10). Of the 3 patients with fatal pulmonary emboli during follow-up 2 had received LMWH and 1 SH. The two drugs were of similar efficacy. The primary end point, the frequency of major bleeding, showed a 23% reduction in the LMWH group, but this difference was not significant. The secondary safety end points revealed that LMWH was significantly better than SH. Fatal pulmonary embolism occurs rarely (0.09%) following discharge from hospital so the cost benefit ratio would not justify prolonged prophylaxis in this setting.

Publication types

  • Clinical Trial
  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Abdomen / surgery*
  • Adult
  • Aged
  • Chi-Square Distribution
  • Double-Blind Method
  • Female
  • Follow-Up Studies
  • Hemorrhage / chemically induced
  • Hemorrhage / epidemiology
  • Heparin / adverse effects
  • Heparin / therapeutic use*
  • Heparin, Low-Molecular-Weight / adverse effects
  • Heparin, Low-Molecular-Weight / therapeutic use*
  • Humans
  • Male
  • Middle Aged
  • Postoperative Complications / epidemiology
  • Postoperative Complications / mortality
  • Postoperative Complications / prevention & control*
  • Risk Factors
  • Thromboembolism / epidemiology
  • Thromboembolism / mortality
  • Thromboembolism / prevention & control*


  • Heparin, Low-Molecular-Weight
  • Heparin