A Comparison Between Low Molecular Weight Heparin (KABI 2165) and Standard Heparin in the Intravenous Treatment of Deep Venous Thrombosis

Abstract

SummaryIn order to study whether a low molecular weight heparin (LMWH) of mw 4000 D is effective in the treatment of deep venous thrombosis (DVT), patients with DVT verified by phlebography were randomized to treatment by continuous intravenous infusion of either unfractionated heparin (UFH) or LMWH. The initial dose was 240 U (anti F Xa)/kg/12 h. TTiis study (study I) was stopped because of major bleeding in 2 newly operated patients in the LMWH group after 27 patients had been treated. The heparin activity measured as F Xa inhibition assayed in retrospect, was found to be much higher in the LMWH group (mean 1.6-2.0 anti F Xa U/ml) than in the UFH group (mean 0.5-0.8 anti F Xa U/ml).A second study was therefore initiated in which the DVT patients were randomly given UFH (240 U/kg/12 h) or LMWH only 120 U (anti F Xa)/kg/12 h, as initial doses (study II). In this study 27 patients could be evaluated, the mean heparin activity still being higher in the LMWH group (0.9-1.2 anti F Xa U/ml) than in the UFH group (0.5-0.7 anti F Xa U/ml).A second phlebographic investigation showed progression of thrombus size in 3 (11%) of the UFH patients of studies I and II (n = 29) and improvement in 14 (48%). There was no progression in any LMWH patient, 6 (50%) had improved in study I and 10 (77%) in study II. The mean decrease of thrombus size score (according to Marder) during treatment did not differ between the 3 groups.Antithrombin III decreased significantly in the UFH group but not in the LMWH groups. Aminotransferases increased in all 3 groups. There was no difference in mean capillary bleeding time between the 3 treatment groups.Although this material is relatively small, our findings suggest that LMWH seems to be of similar effectivity as UFH.

An Open Trial of Enoxaparin in the Treatment of Deep Vein Thrombosis of the Leg

“…It might have been interesting to pool all antiXa activities published in the clinical studies in order to compare all low molecular weight heparin. However, on one hand in the Fragmin's studies, except for the first studies re ported by Bratt et al [27], the dosage of LMWH had been adjusted according to a fixed range of antifactor-Xa activity and on the other hand in the Fraxiparin studies, no biological data were available or published. Thus, it is not possible to compare anti-Xa activities from different LMWH studies.…”

Pharmacology of Heparin and Related Drugs

“…Use of heparins in the treatment of PE and DVT is standard practice and has been subject to refinement over the last half-century, since the key report that UH (albeit in combination with a vitamin K antagonist), compared with no anticoagulant treatment, reduced death and recurrence of thrombosis in a small trial of patients with symptomatic PE (Barritt and Jordan, 1960). Once it had been demonstrated that fixed-dose regimens using LMWH, without the same need for routine monitoring, were as safe as treatment with UH with dose adjustment (based on results of plasma coagulation assays) for DVT (Holm et al, 1986;Prandoni et al, 1992) and PE (Bratt et al, 1985;Hull et al, 1992;Théry et al, 1992), the way was paved for the replacement of UH with LMWH to a large extent. After confirmation of efficacy and safety in larger clinical studies (Dalen, 2002b), LMWH treatment is now the preferred approach in the initial management of VTE (Garcia et al, 2012;Kearon et al, 2012;Cohen et al, 2014) and is used routinely in cases of PE or proximal DVT.…”

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

“…These results correspond with a relative bleeding risk reduction of 21.2% for major and minor bleeding complications. The difference in the overall number of bleeding complications (major and minor combined) is Spontaneous hematomas 7 9 Hematoma after venapunction 4 0…”