Clinical Information

The antithrombotic effect of oral vitamin K antagonists (eg, warfarin) is mediated by reduction in the plasma activity of vitamin K-dependent procoagulant factors II (prothrombin) and X. The intensity of oral anticoagulation therapy with vitamin K antagonists must be monitored and adjusted to a narrow therapeutic range; under medicating increases the risk of thrombosis, while overmedicating increases the risk of bleeding. Such therapy typically is monitored with the prothrombin time/international normalized ratio (INR) system.

Lupus anticoagulants (LAC) are autoantibodies that interfere with phospholipid-dependent clotting tests and most commonly cause prolongation of the activated partial thromboplastin time (APTT). LAC can be associated with a prothrombotic disorder termed the antiphospholipid syndrome. LAC occasionally may cause prolongation of the baseline prothrombin time, rendering the INR system inaccurate for monitoring the intensity of oral anticoagulant therapy. LAC-induced prolongation of the prothrombin time is most commonly seen with recombinant human tissue factor thromboplastins (ie, prothrombin time reagents) with a low international sensitivity index (ISI) such as Innovin or RecombiPlasTin 2G (ISI = 1.0). The chromogenic factor X activity is an alternative assay for monitoring oral anticoagulant therapy. This assay is unaffected by LAC because the assay end point is not a phospholipid-dependent clotting time.

Argatroban is a parenteral direct thrombin inhibitor that is approved for treatment of heparin-induced thrombocytopenia (HIT), an antibody-mediated prothrombotic disorder. Argatroban therapy prolongs the prothrombin time, which also renders the INR inaccurate for monitoring the warfarin effect while transitioning from Argatroban to oral anticoagulant therapy. The chromogenic coagulation factor X activity assay may be used as an alternative to the INR for monitoring and adjusting the warfarin dose during this transition.