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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.

The efficacy and safety of 2 regimens of Fragmin in preventing postoperative venous thromboembolism was compared on 206 consecutive patients, aged 40 years or more, undergoing major abdominal surgery. Ninety-four patients received a single daily injection of 2,500 U of Fragmin for at least 6 postoperative days (group I), while 112 received 5000 U per day in 2 injections of 2,500 U each (group II). In group I 7.4% of patients and in group II 2.6% of patients developed postoperative deep venous thrombosis (DVT); the difference was not statistically significant (p greater than 0.05). There was no significant difference between the 2 groups in terms of numbers of patients having excessive postoperative blood loss, requiring prophylaxis to be discontinued, or measured postoperative drainage. None of the patients in group I, and 2 out of 112 in group II developed wound haematoma. These findings suggest that a single daily injection of 2,500 U of Fragmin may provide an effective prophylaxis against postoperative venous thromboembolism.

A prospective, double-blind, randomized, controlled clinical trial compared the efficacy and safety of fixed combinations of low-molecular weight heparin or standard unfractionated heparin plus dihydroergotamine mesylate in the prevention of deep vein thrombosis in high-risk patients undergoing elective major abdominal surgery. Two hundred patients, with a mean age of 66.6 years and almost half with malignancy, were allocated to receive either 5,000 IU unfractionated heparin plus 0.5 mg dihydroergotamine mesylate twice daily or 1,500 IU low-molecular weight heparin plus 0.5 mg dihydroergotamine mesylate once daily together with one placebo injection per day. Treatment was commenced 2 hours preoperatively and continued for at least 7 days. The incidence of deep vein thrombosis, determined by radiolabelled fibrinogen uptake and phlebography, was 11 percent in the unfractionated heparin plus dihydroergotamine mesylate group and 11.4 percent in the low-molecular weight heparin and dihydroergotamine mesylate group. Neither these figures nor those for major proximal thrombi proved significantly different. Of the four parameters used to assess hemorrhagic complications, only the decrease in postoperative hemoglobin levels in the low-molecular weight and dihydroergotamine mesylate group reached statistical significance. These results indicate that once-daily prophylaxis with a combination of low-molecular weight heparin and dihydroergotamine is safe, effective, and convenient in high-risk patients undergoing major abdominal surgery.