Transitioning from Argatroban to Warfarin in Heparin-Induced Thrombocytopenia: An Analysis of Outcomes in Patients with Elevated International Normalized Ratio (INR)

Abstract

In patients receiving argatroban/warfarin cotherapy and with an elevated INR > 4, the risk for thrombosis exceeds the risk of bleeding. Traditional paradigms concerning elevated INRs and warfarin may need to be redesigned for the patient population on cotherapy with direct thrombin inhibitors.Abbreviated Abstract. The clinical outcomes of 111 patients with INRs > 4 while on combined argatroban (dose < or = 2 mcg/kg/min) and warfarin were evaluated. Adverse clinical outcomes (7 new thrombosis, 3 amputations, 12 deaths and 1 major bleed) occurred in 21 patients. Eleven deaths were due to causes other than thrombosis. Five patients developed new thrombosis while only 1 had major bleeding. The risk for thrombosis exceeds the risk of bleeding in patients with HIT despite an INR > 4.

Treatment and Prevention of Heparin-Induced Thrombocytopenia

“…3.0 while receiving argatroban and warfarin cotherapy had a subtherapeutic INR 4 h after discontinuation of argatroban. 116 The INR should not be interpreted as an indicator of the effect of warfarin alone when administered with argatroban.…”

Erratum

“…112,113 The VKAs should be initiated when platelet counts have normalized to a steady state, then brought on underbridged with a DTI. [114][115][116] There is emerging evidence that the newly developed small molecule anticoagulants including apixaban, dabigatran, edoxaban, otamixaban, and rivaroxaban may become new immediate and long-term treatment options for thrombosis in patients with HIT. 109 …”

Pharmacological Strategies for Inhibition of Thrombin Activity

“…Therefore, the previously established relationship between INR and bleeding risk is altered. As opposed to the usual practice, argatroban should be only discontinued, when an INR > 4 is reached [139,140]. The theoretical INR values on VKA alone can be calculated by means of the measured INR using adequate algorithms [139,137].…”