Monitoring the Direct Thrombin Inhibitors

George A. Fritsma

doi:10.29074/ascls.26.1.54

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George A. Fritsma, MS MT (ASCP)⇑
1. The Fritsma Factor, Your Interactive Hemostasis Resource^SM, Fritsma & Fritsma LLC, Birmingham, AL

Address for Correspondence: George A. Fritsma MS MT (ASCP), The Fritsma Factor, Your Interactive Hemostasis Resource^SM, Fritsma & Fritsma LLC, 153 Redwood Drive, Birmingham, AL 357173, 205-655-0687, George{at}fritsmafactor.com.

Diagram the physiology of the direct thrombin inhibitors
Distinguishe between argatroban and bivalirudin.
Provide the means for monitoring direct thrombin inhibitors.

Extract

The direct thrombin inhibitors (DTIs), intravenous argatroban and bivalirudin and oral dabigatran, reversibly bind and inactivate free and clot-bound thrombin without activating antithrombin (AT, antithrombin III, ATIII), thereby suppressing coagulation at the final stage of the cascade.¹ Argatroban or bivalirudin are substituted for unfractionated heparin (UFH) or low molecular weight heparin (LMWH) when heparin-induced thrombocytopenia with thrombosis (HIT) is suspected or confirmed, as they do not interact with the HIT antibody.² When HIT is suspected, the risk of either venous or arterial thrombosis is 50% for 30 days after heparin withdrawal unless argatroban or bivalirudin is employed. Coumadin is contraindicated in HIT as it is prothrombotic for the first 5 days of administration. Dabigatran has been cleared for prevention of venous thromboembolic (VTE) disease in Europe and Canada and for prevention of stroke in atrial fibrillation in the US. As the first new oral anticoagulant cleared by the FDA since 1954, dabigatran is beginning to take its place in the formulary. Laboratory scientists are challenged to find clinically effective means to monitor its plasma concentration.

Argatroban Argatroban (Novostan®; GlaxoSmithKline, Research Triangle Park, NC) is a non-protein l-arginine derivative with a molecular weight of 527 Daltons.³ Argatroban was FDA-cleared in 1997 for anticoagulation in HIT.⁴ Argatroban may be used for prophylaxis, treatment, and also for anticoagulation during percutaneous cardiac intervention (PCI, cardiac catheterization) for patients with HIT.⁵

The physician initiates the argatroban intravenous infusion at 2 μg/kg/min or in patients with liver disease at 0.5 μg/kg/min. During PCI, a bolus of…

ABBREVIATIONS: APTT or PTT - activated partial thromboplastin time; AT - antithrombin; CAD – coronary artery disease; DTI - direct thrombin inhibitor; DVT - deep venous thrombosis; ECT-ecarin clotting time; FDA - US Food and Drug Administration; HIT - heparin-induced thrombocytopenia with thrombosis; INR - international normalized ratio; LMWH - low molecular weight heparin; PE - pulmonary embolism; PCI - percutaneous intervention (cardiac catheterization); PiCT - prothrombinase-induced clotting time; PT - prothrombin time; RI - reference interval; RUO - research use only; TCT - thrombin clotting time; TPA - tissue plasminogen activator; UFH - unfractionated heparin; VTE - venous thromboembolism.