25.3.1.2 Anticoagulants

The second group of antithrombosis drugs are the anticoagulants. In the process of forming a thrombus, fibrinogen is converted to fibrin by thrombin, the end point of the clotting cascade. The cascade is a series of reactions that sequentially transform various plasma fractions to their active enzymic form. They ultimately produce activated clotting factor Xa which converts prothrombin to thrombin. Anticoagulants exert their action by reducing the action of specific clotting factors, as in the case of the heparins, or by interfering with clotting factor synthesis, as demonstrated by the vitamin K antagonists.

Heparin and its lower molecular weight forms (enoxaparin, dalteparin) exert their effects by binding to and activating antithrombin III. Activation of this enzyme results in thrombin inactivation and subsequent blocking of clot formation. These drugs are indicated for deep vein thrombosis, pulmonary embolism and acute coronary syndrome. Adverse effects of the heparins include haemhorrage and thrombocytopaenia.

The coumarin anticoagulants (warfarin) exert their actions by inhibiting the synthesis of vitamin K dependent coagulation factors (VII, IX, X, II) perturbing the clotting cascade. They are used to prevent the progression or recurrence of deep vein thrombosis and pulmonary embolism. The main adverse reaction to warfarin treatment is haemorrhage. Warfarin has numerous drug interactions that may potentiate or attenuate its actions. As such warfarin administration should be monitored closely.