Clinical aspects on treatment of deep venous thrombosis with a low molecular weight heparin

Abstract: Dalteparin is a low molecular weight heparin (LMWH) with a mean mw of 4-6000 D. Compared to unfractionated heparin (UFH), a higher bioavailability, a longer half-life and a more predictable dose-response is achieved after subcutaneous injections. In three clinical studiees including 424 patients with deep venous thrombosis (DVT) in the lower extremity, we have shown that one daily subcutaneous injection of dalteparin in a fixed dose according to body weight is as effective as a continuous intravenous i.v. infusion of unfractionated heparin (UFH) in patients with DVT in the lower extremity. Monitoring of patients treated with dalteparin measuring anti FXa-activity is not necessary. During the first week of treatment with either dalteparin or UFH, a reduction of thrombus size was observed in about 60% of the patients and < 10% showed progress of thrombus after I week. Repeated venography after 6 months showed improvement in > 90% of the patients, and complete lysis was achieved in nearly 40% of the patients. No difference comparing treatment with UFH or dalteparin was observed. The result on venography after 6 months, evaluated by Marder score, did not correlate to the risk for recurrent VTE, but the post-thrombotic score at 4-7 years of follow-up was strongly correlated to the venographic result after 6 months (paper 5). Analysis of risk-factors for recurrent VTE during a 4-14 years of follow-up showed that a temporary risk-factor for DVT (previous surgery, temporary immobilization, oral contraceptives or estrogen substitution), a longer duration of treatment with oral anticoagulants and an initial treatment with dalteparin were significantly associated with a lower risk for recurrent VTE. Malignant disease diagnosed during the follow-up period was associated with an increased risk for recurrent VTE. APC-resistance, the associated FV-gene mutation (FV:R506Q) and fibrinolytic parameters (plasminogen activator inhibitor -1 and tissue plasminogen activator antigen) did not increase the risk for recurrent VTE. During a follow-up period of 5-14 years, 40,7% of the patients had died (paper 5). Most of the deaths were related to malignant disease and to cardio-cerebrovascular events. 5% of the deaths were caused by VTE. No difference in mortality was observed comparing patients treated with dalteparin or UFH.