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.

SummaryA low molecular weight heparin (LMW-heparin) with a mean molecular weight of 4900 dalton was prepared by controlled enzymatic depolymerization of conventional porcine mucosal heparin. The effects of 2,500, 5,000 and 10,000 U (Xal; 29,58 and 116 mg) on factor Xa inhibition (Xal), factor Ila inhibition (Hal), APTT, AT III and platelet count were compared to those of 5,000 U (Xal; 26 mg) of conventional heparin given s. c. to 6 healthy volunteers. 5,000 U (Xal; 58 mg) of LMW-heparin was given i. v. A dose related response with regard to the Xal and the Ila-inhibitory activities with peak values at 4 hours after the s. c. injections was obtained. An increase of the Xal/IIal ratio over the time after injection was seen only after i. v. administration of the LMW-heparin. The APTT was only slightly prolonged and remained within normal range after s. c. injection. AT III and platelet counts were unaffected. The biological half life of the LMW-heparin was 111 minutes if assayed by Xa inhibition, 76 minutes if assayed by Ila inhibition and 40 minutes if assayed by APTT. A strong correlation between the Xal activities obtained and body weight was seen, indicating that LMW-heparin should be administered individually according to body weight.

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A prospective randomized double-blind trial was performed comparing conventional low-dose heparin with a low molecular weight heparin fragment for thromboprophylaxis in elective general abdominal surgical patients. The first dose of the heparin fragment was given the evening before surgery, and further doses were given thereafter every evening. There were 1002 analysable patients, 826 having received correct prophylaxis. Of these 1002 patients, 64 per cent were operated on for malignant disease. A total of 20 patients died, 10 in each group. The frequency of deep vein thrombosis was significantly reduced among patients with correct prophylaxis with the heparin fragment (9.2-5.0 per cent, P = 0.02) [corrected]. The frequency of bleeding was 6.7 per cent among the heparin fragment patients and 2.7 per cent among the patients given conventional heparin (P = 0.01), but all bleeds were of minor degree and there was no difference in the reoperation rate for bleeding, or in the transfusion requirements. Local pain at the injection site was reported significantly less often among patients given the heparin fragment.

This article reviews the problem of bleeding in connection with epidural/spinal anaesthesia, with special emphasis on the use of low molecular weight heparins for thromboprophylaxis. There are methodological difficulties to studying the problem in a scientifically correct way because of the rarity of the complication. However, from the data in the literature there are no indications of an increased risk in using the combination of low molecular weight heparin in prophylactic doses and epidural/spinal anaesthesia. So far, there is only a single case report, of spinal haematoma, although low molecular weight heparins have been used in combination with epidural/spinal anaesthesia in at least 1,000,000 patients. In controlled studies, at least 10,000 patients have been given the combination without complications.