Current Vascular Pharmacology

Dimitri P. Mikhailidis  
Academic Head, Deptartment of Clinical Biochemistry
Royal Free Hospital Campus
University College London Medical School
University College London (UCL)
Pond Street
London, NW3 2QG


Biochemical Strategies to Anticoagulation: A Comparative Overview

Author(s): Arthur J. Chu

Affiliation: Surgery Department, WayneState University, School of Medicine, Detroit, Michigan 48201, USA


Hypercoagulability is widely associated with sepsis, inflammation, diabetes, cancers, aging, and many pathological conditions, resulting in life-threatening disseminated intravascular coagulation (DIC), venous thrombosis, thromboembolism, cardiovascular complications, or even deadly multiple organ failure. Relieving coagulation dysfunction is not only a task for research scientists but also a challenge for physicians. The development of effective anticoagulants is under way with the basic understanding of the pathophysiology of hypercoagulable state. In this overview, various anticoagulants will be discussed according to the proposed inhibitory target-sites along the extrinsic pathway that is believed to play an integral role in homeostasis. Anticoagulants generally fall into two broad categories as natural or pharmacological ones. Antithrombin (AT), activated protein C (APC), and tissue factor pathway inhibitor (TFPI) mainly constitute the natural anticoagulant system apart from the recently reported physiological components such as lipoproteins, sphingosine, thrombomodulin (TM) or cellular Marcks protein. Pharmacological anticoagulants include warfarin, FVIIa inhibitors, FXa inhibitors, and thrombin inhibition by its direct inhibitors or heparins. In addition, a group of novel compounds inhibiting TF-dependent FVII activation result in anticoagulation; such upstream downregulation in the extrinsic pathway awaits further research to establish their in vivo benefits. The molecular genetic approaches such as developing soluble TF, FVII and thrombin mutants provide unique downregulation. Anticoagulation also extends its significance to anti-inflammation, making broad impacts on the improvement of human health.

Keywords: hypercoagulability, thrombosis, tissue factor, fvii, fx, thrombin, anticoagulant, inflammation

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Article Details

Page: [199 - 228]
Pages: 30
DOI: 10.2174/1570161043385673
Price: $58