Early Identification of Argatroban Resistance and the Consideration of Factor VIII

Argatroban, a synthetic, parenteral, nonheparin anticoagulant, is a direct thrombin inhibitor indicated for the prophylaxis or treatment of venous thromboembolism (VTE) in patients with heparin-induced thrombocytopenia with thrombosis (HITT) and for use during percutaneous coronary intervention (PCI) in patients who have or are at risk for developing HITT. Although heparin resistance occurs in approximately 0.5% to 5% of heparin-treated patients and is well documented in the literature, argatroban resistance is limited to a single case report. The objective of this case is to describe a case in which argatroban resistance was suspected in a patient with critical limb ischemia.

This is a case report of a single patient.

A 68-year-old female admitted for critical limb ischemia requiring vascular intervention was treated for presumed HITT with argatroban. A therapeutic activated partial thromboplastin time (aPTT) was not attained (31 seconds) despite multiple uptitrations of the dose to 2.8 μg/kg/min (adjusted based on the institutional protocol and with consideration of organ dysfunction). A coagulopathy workup revealed a high level of factor VIII (265%).

This case supports early assessment of factor VIII levels and the consideration of argatroban resistance and in patients who have a subtherapeutic aPTT, despite multiple increases in dose with an elevated factor VIII level. Early identification should prompt the use of an alternative anticoagulant to ensure efficacy.