Low-molecular-weight heparins (LMWHs) are now universally accepted as drugs of choice
for postsurgical prophylaxis and treatment of deep vein thrombosis (DVT). Currently,
these agents are also being developed for the treatment of various cardiovascular
conditions. Because of manufacturing differences, each of the LMWHs exhibits distinct
pharmacologic and biochemical profiles. The specific activity of these agents in anticoagulant
assays ranges from 35 to 45 anti-IIa U/mg, whereas the activity in terms of anti-Xa
units is designated as 80 to 145 U/mg. These LMWHs are also capable of producing product-specific
dose- and time-dependent antithrombotic effects in animal models of thrombosis. Although
the ex vivo effects are initially present at dosages that are antithrombotic, these
agents have been found to produce sustained antithrombotic effects without any detectable
ex vivo anticoagulant actions. In experimental animal models and various clinical
trials, these agents also have been found to release tissue factor pathway inhibitor
and von Willebrand factor. In addition, LMWHs have been reported to produce fibrinolytic
effects. The effect of repeated administration also exhibits product-based augmentation
of the antithrombotic and hemorrhagic effects. Several new agents are being investigated
as possible substitutes for heparins. These include anti-thrombin, anti-Xa, anti-TF
(tissue factor), heparinoids, oral formulations of heparin, activated protein C, and
biotechnologically derived serpins. These agents may not have the broad clinical spectrum
as that observed with the heparins. More recently, several pharmaceutical companies
have produced generic LMWHs.
KEYWORDS
Low-molecular-weight heparins - anticoagulants - antithrombotic - differentiation
- generic drugs
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Jawed FareedPh.D.
Departments of Pathology and Pharmacology, Hemostasis and Thrombosis Research Laboratories,
Loyola University Chicago
2160 S. First Avenue, Maywood, IL 60153
Email: jfareed@lumc.edu
