Prothrombinase - Anticoagulant Drugs

Anticoagulant Drugs

Inhibition of Factor Xa prevents thrombin activation, thereby preventing clot formation. Thus, Factor Xa is used as both a direct and indirect target of several anticoagulant drugs. For example, the drug Fondaparinux is an indirect inhibitor of Factor Xa. Fondaparinux binds to antithrombin III and activates the molecule for Factor Xa inhibition. In fact, Fondaparinux imparts an increased affinity of antithrombin III to Factor Xa, and this increased affinity results in a 300-fold increase in the antithrombin III inhibitory effect on Factor Xa. After the antithrombin III binds to Factor Xa, the Fondaparinux is released and can activate another antithrombin. Another drug that indirectly inhibits Factor Xa is Idraparinux. Idraparinux also binds antithrombin III, however with a 30-fold increase in affinity as compared to Fondaparinux. Idraparinux has an increased half-life as compared to Fondaparinux and can be administered on a weekly basis, whereas Fondaparinux must be subcutaneously injected daily.

Rivaroxaban and Apixaban are direct Factor Xa inhibitors.

Rivaroxaban and Apixaban bind to the active site of Factor Xa, regardless of whether Factor Xa is bound in the prothrombinase complex or is in its free form. These direct Factor Xa inhibitors can be administered orally, as can dabigatran etexilate which is a direct thrombin inhibitor.

While Fondaparinux is currently used as an FDA approved anticoagulant drug, Idraparinux, Rivaroxaban, Apixaban, and Dabigatran Etexilate are still in the stages of clinical trials.