Treatment of acute venous thromboembolism with low molecular weight heparin (Fragmin). Results of a double-blind randomized study.

Abstract

We performed a prospective, randomized, double-blind trial in 194 unselected patients to determine the safety and efficacy of low molecular weight heparin (Fragmin) compared with standard heparin as the initial treatment of acute venous thromboembolism. Ninety-eight patients received continuous intravenous heparin, and 96 patients received Fragmin for 5-10 days. Doses were adjusted to maintain anti-Xa levels between 0.3 and 0.6 unit/ml for patients with a high risk for a bleeding complication and between 0.4 and 0.9 unit/ml for patients with a low risk for bleeding. Treatment was stopped when a therapeutic level of anticoagulation (International Normalized Ratio >3.5) was reached with coumarins. Thirteen patients in the heparin group and 10 patients in the Fragmin group had a major bleeding complication. The incidence of major and minor bleeding complications combined decreased from 48.9% to 38.5% (95% confidence interval for the dilference, -3.5% to +24.2%), corresponding with a relative bleeding risk reduction of 21.2%. There were no significant differences in efficacy as defined by new high-probability defects on repeat ventilation-perfusion scintigraphy of the lung in 80 patients: six of 46 patients in the heparin group and 3 of 34 patients in the Fragmin group had new defects (95% confidence interval for the difference, -9.4% to + 17.8%). We conclude that low molecular weight heparin (Fragmin) given in adjusted, continuous, and intravenous doses is safe and effective as initial treatment of acute venous thromboembolism compared with heparin. There is a trend in risk reduction for bleeding in favor of low molecular weight heparin, a trend, however, that is smaller than expected compared with animal studies. (Circulation 1989;80:935-940) H eparin is used in relatively large doses in the management of thromboembolic disease with the aim of preventing extension and embolization of venous thrombi. The treatment, however, is associated with an appreciable risk of hemorrhage. This has prompted research to improve the benefit to risk ratio of the drug.Heparin acts as an anticoagulant by accelerating the complex formation between antithrombin III and various activated clotting factors, among which factor Xa and thrombin are the most important. Fractionation of the polydisperse heparin according to molecular size has led to the development of low molecular weight heparin preparations with an increased anti-Xa to antithrombin ratio.1 These low molecular weight heparins have been shown to

Anticoagulation for the initial treatment of venous thromboembolism in patients with cancer

“…[17][18][19][20] We contacted the authors of the remaining 19 articles to request cancer subgroup data: One author provided us with the data 21 ; another author indicated that the data were not available anymore 22 ; we used the cancer subgroup data for 7 articles, 23-29 because they were reported in 2 published systematic reviews 5,8 ; and we were not able to obtain any outcome data for the remaining studies. [30][31][32][33][34][35][36][37][38][39] Thus, of 24 studies with cancer patients' subgroups, we were able to obtain data for 13 studies. Agreement between authors for study eligibility was excellent (kappa of 0.94).…”

Retroperitoneal haematoma and tinzaparin

“…Concomitant use of non-steroidal anti-inflammatory drugs or antiplatelet agents with LMWH is also known to increase the risk of bleeding 3 . Retroperitoneal haematoma, a severe form of bleeding which can be potentially fatal, has been reported with the use of the LMWH enoxaparin 5 and dalteparin 6 . In the case described here, spontaneous bilateral retroperitoneal haematoma developed after using the LMWH tinzaparin, to treat venous thrombosis in a patient with no known risk factors for bleeding.…”

New developments in the treatment of deep venous thrombosis

“…First, the change in thrombus size was assessed by repeating venography at the end of the course of treatment [33][34][35][36][37]: LMWH were as effective as SH. Second, most studies used the occurrence of the symptomatic recurrent DVT as end-point; there was a strong trend for LMWH to be more effective and safer than SH [38][39][40][41]. Two meta-analyses of these trials found similar trends indicating improved efficacy and safety with LMWH [42,43], It is uncertain if the favorable outcomes of treatment with different LMWH can be extrapolated to ail other types of LMWH [24,42,44], Also it is not certain whether there is bioequivalence between all products.…”

“…As a consequence similar studies with different types of LMWH should be performed. Fi nally it should be noted that only a few studies used a once-daily regimen of LMWH [39,41,45], the other studies twice daily. Currently LMWH once versus twice daily are being compared.…”

“…The risk of bleeding is increased with an increased heparin dose, but also other factors such as recent surgery, trauma, peptic ulcer, malignancy or an haemostatic abnormality are important. Most tri als comparing SH to LMWH suggest that LMWH 40 Medicine 50(19971 36-45 cause fewer bleeding complications [20,[39][40][41], This embolism despite anticoagulation [8,62,63]. No data is probably due to a lower anti-IIa/anti-Xa ratio of LMWH than of SH.…”