Low molecular weight heparin started before surgery as prophylaxis against deep vein thrombosis: 2500 versus 5000 Xal units in 2070 patients

Abstract

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.

The heparins and cancer: review of clinical trials and biological properties

“…DVT rates fell from 14.9% in those receiving 2500 IU units to 8.5% in patients receiving 5000 IU. 37 This study was the first to demonstrate that increased doses of LMWHs can improve thrombo-prophylactic efficacy in cancer patients without increasing the risk of bleeding complications.…”

Coagulation and cancer: Implications for diagnosis and management

“…52 Two studies have focused on the efficacy of LMWH in the prevention of VTE in cancer patients undergoing abdominal operation, showing a safety profile broadly similar for the LMWH and LDH. 5,26 Finally, although the risk of VTE associated with chemotherapy is recognized, information about its incidence and the influence of a particular chemotherapy regimen on its occurence are only available for women with breast carcinoma. A recent prospective double-bind randomized study showed that during chemotherapy lowdose warfarin (1mg.)…”

Venous thromboembolism prophylaxis in cancer patients — guidelines focus on surgical patients

“…In a study of 1.375 patients, of whom 70% were patients with cancer, two prophylactic doses of dalteparin (2500 U and 5000 U) were used. The dose 5000 U was more effective in preventing postoperative VTE than the 2500 U dose (postoperative VTE of 8.5% vs. 14.9%; p < 0.001) [73].…”