LOW-MOLECULAR-WEIGHT HEPARIN STARTED BEFORE SURGERY AS PROPHYLAXIS AGAINST DEEP-VEIN THROMBOSIS - 2500 VERSUS 5000 XAI UNITS IN 2070 PATIENTS

The optimal administration regimens of low molecular weight heparins ( LMWHs) have not yet been established. The aim of this study was to com pare the efficacy and safety of 2500 and 5000 XaI units of the LMWH da lteparin 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 stud y was designed as a prospective, randomized, double-blind, multicentre trial. Some 66.4 per cent of patients were operated on for a malignan t disorder. The primary endpoint was deep vein thrombosis (DVT) detect ed with the fibrinogen uptake test. Bleeding complications were record ed and classified. Analysis was made both on an intention to treat bas is 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 pati ents. The incidence of DVT was significantly lower in patients given 5 000 XaI units, this being true for both correct prophylaxis (6.8 versu s 13.1 per cent, P < 0.001), on an intention to treat basis (6.6 versu s 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 cen t) died within 30 days with no difference between the groups. There we re two cases of fatal pulmonary embolism. The frequency of bleeding co mplications in the whole series was higher in patients randomized to 5 000 XaI units (4.7 versus 2.7 per cent, P = 0.02), although this was n ot 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 unit s started in the evening before surgery has a good thromboprophylactic effect in high-risk general surgery at the cost of a small bleeding r isk. In patients with malignant disease there was no increased risk of bleeding. The overall frequency of fatal pulmonary embolism with dalt eparin is extremely low, even in this high-risk group of patients.