Low-molecular-weight heparins for the treatment of deep-vein thrombosis

The pharmacologic characteristics of low-molecular-weight (LMW) heparins and unfractionated heparin are reviewed, and clinical trials comparing LMW heparins with unfractionated heparin for the initial treatment of deep-vein thrombosis (DVT) are described. LMW heparins are derived from native heparin and range in mass from 3000 to 8000 daltons. All LMW heparins contain the antithrombin III-specific pentasaccharide unit found on unfractionated heparin. LMW heparins are stronger inhibitors of factor Xa than unfractionated heparin, but their mechanisms of action, like that of unfractionated heparin, is predominantly the inhibition of thrombin. The efficacy of LMW heparins in the prophylaxis of DVT is not correlated with activated partial thromboplastin time (APTT); monitoring of APTT or anti-factor Xa may not be necessary. Compared with unfractionated heparin, LMW heparins have a lower affinity for heparin cofactor II, platelet factor 4, von Willebrand factor, and vascular epithelium. Subcutaneously administered LMW heparins are more bioavailable than s.c. unfractionated heparin. In clinical trials in patients with DVT, LMW heparins (dalteparin, enoxaparin, nadroparin, and tinzaparin) have resulted in venography scores similar to those obtained with unfractionated heparin. Frequencies of recurrent thromboembolism and bleeding complications were also similar. Dalteparin and logiparin were effective when administered in single daily subcutaneous doses; this could lead to lower treatment costs. Additional studies are needed to compare LMW heparins and unfractionated heparin with respect to efficacy, bleeding complications, mortality, and cost. LMW heparins may be valuable alternatives to unfractionated heparin for the treatment of DVT.