Low molecular weight heparins: are they different?
In addition to their use in postsurgical and medical prophylaxis of deep vein thrombosis (DVT), low molecular weight heparins (LMWHs) are being developed for cardiovascular and cerebrovascular indications. Because of manufacturing differences, each LMWH exhibits distinct pharmacological and biochemical profiles that may influence clinical performance. The specific activity of these agents in anticoagulant assays ranges from 35 to 45 anti-IIa U/mg or 80 to 120 anti-Xa U/mg. LMWHs are capable of producing product-specific dose- and time-dependent antithrombotic effects in animal models of thrombosis. While the ex vivo effects are initially present at antithrombotic doses, these agents have been found to produce sustained antithrombotic effects without any detectable ex vivo anticoagulant actions. In experimental animal models and in various clinical trials, these agents have also been found to release tissue factor pathway inhibitor (TFPI) after both intravenous and subcutaneous administration. Repeated administration of LMWHs produces progressively stronger antithrombotic effects. However, the hemorrhagic responses vary and are largely product dependent. The product-dependent release of TFPI following intravenous and subcutaneous administration in a primate model also demonstrates the relevance of this inhibitor to the actions of LMWHs. The effect of repeated administration of LMWH mimicking the postsurgical prophylaxis of DVT exhibited product-based augmentation of the antithrombotic or hemorrhagic effects.
Fareed
J
J
Department of Pathology and Pharmacology, Loyola University Medical Center, Maywood, Illinois, USA. JFareed@luc.edu
Hoppensteadt
D
D
Jeske
W
W
Clarizio
R
R
Walenga
J M
JM
D000818:Animals; D000925:Anticoagulants / Q000627:therapeutic use; D003327:Coronary Disease / Q000188:drug therapy*; D004195:Disease Models, Animal; D005260:Female; D005343:Fibrinolytic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D006495:Heparin, Low-Molecular-Weight / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D011817:Rabbits; D012680:Sensitivity and Specificity
D000925:Anticoagulants; D005343:Fibrinolytic Agents; D006495:Heparin, Low-Molecular-Weight