ARE THE AVAILABLE LOW-MOLECULAR-WEIGHT HEPARIN PREPARATIONS THE SAME

Low molecular weight heparins (LMWHs) are now universally accepted as drugs of choice for post-surgical prophylaxis of DVT. Currently these agents are also being developed for therapeutic and cardiovascular ind ications, Because of manufacturing differences, each of the LMWHs exhi bit distinct pharmacologic and biochemical profiles, The specific acti vity of these agents in the anticoagulant assays ranges from 35 to 45 anti-IIa U/mg whereas the specific activity in terms of anti-Xa units is designated as 80 to 120 anti-Xa U/mg. These LMWHs are capable of pr oducing product specific dose and time dependent antithrombotic effect s in animal models of thrombosis, While the ex vivo effects are initia lly present at dosages that are antithrombotic, these agents have been found to produce sustained antithrombotic effects without any detecta ble ex vivo anticoagulant actions, In the experimental animal models a nd in various clinical trials, these agents have also been found to re lease tissue factor pathway inhibitor (TFPI) after both intravenous (I V) and subcutaneous (SC) administration, Repeated administration of LM WHs produces progressively stronger antithrombotic effects; however, t he hemorrhagic responses vary and are largely dependent on products. T he release of TFPI following IV and SC administration in a primate mod el also demonstrated the product individuality and the relevance of th is inhibitor to the actions of LMWHs. The effect of repeated administr ation mimicking the post-surgical prophylaxis of DVT also exhibited pr oduct based augmentation of the antithrombotic or hemorrhagic effects, Antithrombotic and hemorrhagic studies are reported that compare the pharmacologic profile of some of the available LMWHs, Product individu ality in terms of relative potency in different assays and the failure of standardization protocols to provide any guidelines for product su bstitution and prediction of the clinical effects is also addressed.