Review article: Coagulation cascade and therapeutics update: Relevance to nephrology. Part 1: Overview of coagulation, thrombophilias and history of anticoagulants

Aug 14, 2009Nephrology (Carlton, Vic.)

Blood Clotting Process, Blood Clot Risks, and Anticoagulant History: An Overview Relevant to Kidney Health

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Abstract

Coagulation is a regulated sequence involving the activation of zymogens to achieve haemostasis in an anticoagulant environment.

The process begins when circulating factor VII/VIIa interacts with tissue factor, triggering a cascade that amplifies the initial signal.
This cascade results in the conversion of fibrinogen to fibrin, leading to clot formation.
Anticoagulant mechanisms exist to regulate this process and prevent excessive clotting.
Pathological conditions can disrupt these regulatory mechanisms, potentially leading to thrombosis.
Current anticoagulant therapies are evolving towards targeted treatments based on an understanding of specific coagulation factors.
Future medications may shift to become first-line therapies for thrombosis in the next decade.

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Coagulation involves the regulated sequence of proteolytic activation of a series of zymogens to achieve appropriate and timely haemostasis in an injured vessel, in an environment that overwhelmingly favours an anticoagulant state. In the non-pathological state, the inciting event involves exposure of circulating factor VII/VIIa to extravascularly expressed tissue factor, which brings into motion the series of steps which results in amplification of the initial stimulus, culminating in the conversion of fibrinogen to fibrin and clot formation. The precisely synchronized cascade of events is counter-balanced by a system of anticoagulant mechanisms, which serve to ensure that the haemostatic effect is regulated and does not extend inappropriately. Conversely, in pathological states, these events can escape normal control mechanisms, due to either inherited or acquired defects, which lead to thrombosis. Current anticoagulant therapy, although based on medications that have been in existence for upwards of 80 years, is moving towards targeted therapy for specific coagulation factors and events in the coagulation cascade, based on the current knowledge of the main triggers and key events within the series of reactions that culminates in haemostasis. It remains to be seen whether these newer medications will become first-line therapies for thrombosis in the coming decade. This review aims to elucidate the main events within the coagulation cascade as it is currently understood to operate in vivo, with a brief discussion focusing on hypercoagulable states, and also a short review of the history of anticoagulants as they relate to this model.

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