Argatroban in heparin-induced thrombocytopenia: rationale for use and place in therapy

Abstract

Heparin-induced thrombocytopenia (HIT) is a recognized complication of heparin and requires urgent detection and treatment. HIT can be divided into two types, type I and type II, with type I being a transient decrease in platelet count without clinical consequence. For the purpose of this review, the term HIT refers to the immune-mediated type II that causes paradoxical thrombo-emboli. The aim of this review is to familiarize clinicians with a specific direct thrombin inhibitor, argatroban, in the treatment of HIT. Argatroban has been successfully employed in treating HIT in many different subsets of patients, including those with endstage renal disease on hemodialysis and in patients undergoing percutaneous coronary intervention and those with multiorgan dysfunction syndrome.

Pulmonary embolism and heparin-induced thrombocytopenia successfully treated with tissue plasminogen activator and argatroban

“…Typical dosing is 2-10 µg/kg/min with no loading dose, and the goal aPTT is usually 40-80 seconds. 6 It successfully treated the patient who presented in this case, as she has had no further known thromboembolic events to this date. In regard to PE, though tPA is typically given as 100 mg over 2 hours, there has been reported thrombolysis with no increase in bleeding when given in less time.…”

Update on argatroban for the prophylaxis and treatment of heparin-induced thrombocytopenia type II

“…Argatroban is a synthetic DTI derived from L-arginine that selectively and reversibly binds to the thrombin active site, inhibiting its catalytic activity 10,18,22–26. It is a small molecule (molecular weight approximately 500 Da) that inhibits thrombin, both free and clot-associated, because it acts independently of antithrombin, like the other DTIs.…”

“…The APTT should be performed 2 hours after the initiation of infusion and after every dosage adjustment until the steady-state APTT is 1.5–3.0 times the initial baseline value. Nevertheless, the maximum dosage should not exceed 10 μg/kg/minute 2,8,18,22,23,25…”

“…Ideally, it would be beneficial if laboratories were able to measure actual argatroban concentration in patient’s serum, but this is not yet available. High doses of argatroban are an option, if needed, with close APTT monitoring 18,51…”

“…The mortality associated with heparin-induced thrombocytopenia is approximately 5%–10%, usually secondary to thrombotic complication 5,10. Without alternate anticoagulation, the risk of thromboembolic complication can be seen in 30%–75% 18,19…”