Pharmacology for Anaesthesia and Intensive Care

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Drugs affecting coagulation

Anti-platelet drugs


Heparins and protamine


Oral anticoagulants


Drugs affecting the fibrinolytic system

Physiology

Haemostasis is complicated. Two models are currently used to explain what is

thought to occur.

The classical model

This has three elements: platelets, the coagulation cascade and fibrinolysis. The

first two are involved in preventing haemorrhage by thrombus formation, while

fibrinolysis is an essential limiting mechanism.

Thrombus formation is initially dependent on platelet adhesion, which is

triggered by exposure to subendothelial connective tissue. The von Willebrand

factor, which is part of the main fraction of factor VIII, is essential in this process.

Subsequent platelet aggregation and vasoconstriction is enhanced by the release

of thromboxane A 2 (TXA 2 )fromplatelets. Adjacent undamaged vascular endothe-

lium produces prostacyclin (PGI 2 ), which inhibits aggregation and helps to localize

the platelet plug to the damaged area. The localized primary platelet plug is then

enmeshed by fibrin converting it to a stable haemostatic plug.

The coagulation cascade is formed by an intrinsic and extrinsic pathway, which

converge to activate factor X and the final common pathway (Figure23.1). The intrin-

sic pathway is triggered by the exposure of collagen, thereby activating factor XII,

while the extrinsic pathway is triggered by leakage of tissue factors, activating factor

VII.

Venous thrombus consists mainly of a fibrin web enmeshed with platelets

and red cells. Arterial thrombus relies more on platelets and less on the fibrin

mesh.

Acrucial part of this process is its limitation to the initial site of injury. Circulating

inhibitors, of which anti-thrombin III is the most potent, perform this function. In