Minimal Prolongation of Prothrombin Time with Extended Exposure to Argatroban

In the setting of acute heparin-induced thrombocytopenia (HIT), argatroban is one of the initial anticoagulants of choice, which is eventually bridged to warfarin over a period of 5 or more days. Argatroban prolongs prothrombin time (PT) and increases international normalized ratio (INR). However, the effects of prolonged argatroban exposure on the PT and INR are not known. We describe an unusual case of prolonged argatroban treatment in a patient with heparin-induced thrombocytopenia with thrombosis syndrome (HITTS) resulting in a minimal elevation of the INR. The patient received a total of 58 days of argatroban and was resistant to warfarin therapy, requiring a 13-day bridge to achieve a therapeutic INR of 2.0 to 3.0. Ultimately, argatroban was successfully transitioned to warfarin therapy when the INR was 2.7 on both agents, producing the confirmatory true INR of 2.4. Argatroban and warfarin cotherapy did not increase the INR beyond 4.0 after prolonged argatroban exposure. Clinicians should consider this unusual response in other cases of prolonged argatroban use, and monitor INR carefully during warfarin and argatroban cotherapy. The use of other methods to monitor anticoagulant therapy, such as chromogenic factor X assay (CFX), may be helpful in this setting.