CURRENT PERSPECTIVE ON LOW-MOLECULAR-WEIGHT HEPARINS

The introduction of low molecular weight (LMW) heparins has added a ne w perspective to the prophylactic and therapeutic management of thromb oembolic disorders. These agents are now universally accepted as drugs of choice for postsurgical prophylaxis of deep venous thrombosis (DVT ). LMW heparins are being developed for various therapeutic and cardio vascular indications. The specific activity of these agents in the ant icoagulant assays is 35-45 anti-IIa U/mg, whereas the specific activit y in terms of anti-Xa units is designated as 80-120 anti-Xa U/mg. Thes e LMW heparins are capable of producing dose- and- time dependent anti thrombotic effects in animal models of thrombosis. Although the ex viv o effects are initially present at antithrombotic dosages, these agent s have been found to produce sustained antithrombotic effects without any detectable ex vivo anticoagulant actions. In the experimental anim al models and in various clinical trials, these agents have also been found to release tissue factor pathway inhibitor (TFPI) after both int ravenous and subcutaneous administration. Repeated administration of L MW heparins produces progressively stronger antithrombotic effects; ho wever, the hemorrhagic responses vary. The release of TFPI after i.v. and s.c. administration in a primate model was investigated to demonst rate the relevance of this inhibitor to the actions of LMW heparins. T he effect of repeated administration mimicking the postsurgical prophy laxis of DVT was also studied in terms of potential augmentation of th e antithrombotic or hemorrhagic effects of these agents. Antithromboti c and pharmacologic studies are reported that compare the pharmacologi c profile of some of the available LMW heparins. A synopsis on the pot ential additional usage of these agents, including home therapy, is al so presented.