Differentiation of low-molecular-weight heparins: impact on the future of the management of thrombosis.

Abstract:

: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.

journal_name

Semin Thromb Hemost

authors

Fareed J,Ma Q,Florian M,Maddineni J,Iqbal O,Hoppensteadt DA,Bick RL

doi

10.1055/s-2004-823007

subject

Has Abstract

pub_date

2004-02-01 00:00:00

pages

89-104

eissn

0094-6176

issn

1098-9064

journal_volume

30 Suppl 1

pub_type

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