Prolonged elevation of plasma argatroban in a cardiac transplant patient with a suspected history of heparin‐induced thrombocytopenia with thrombosis

Abstract

BACKGROUND: Direct thrombin inhibitors (DTIs) provide an alternative method of anticoagulation for patients with a history of heparin-induced thrombocytopenia (HIT) or HIT with thrombosis (HITT) undergoing cardiopulmonary bypass (CPB). In the following report, a 65-year-old critically ill patient with a suspected history of HITT was administered argatroban for anticoagulation on bypass during heart transplantation. The patient required massive transfusion support (55 units of red blood cells, 42 units of fresh-frozen plasma, 40 units of cryoprecipitate, 40 units of platelets, and three doses of recombinant Factor VIIa) for severe intraoperative and postoperative bleeding. STUDY DESIGN AND METHODS: Plasma samples from before and after CPB were analyzed postoperatively for argatroban concentration using a modified ecarin clotting time (ECT) assay. RESULTS: Unexpectedly high concentrations of argatroban were measured in these samples (range, 0-32 mg/mL), and a prolonged plasma argatroban half life (t1/2) of 514 minutes was observed (published elimination t1/2 is 39-51 minutes [Յ181 minutes with hepatic impairment]). CONCLUSIONS: Correlation of plasma argatroban concentration versus the patient's coagulation variables and clinical course suggest that prolonged elevated levels of plasma argatroban may have contributed to the patient's extended coagulopathy. Because DTIs do not have reversal agents, surgical teams and transfusion services should remain aware of the possibility of massive transfusion events during anticoagulation with these agents. This is the first report to measure plasma argatroban concentration in the context of CPB and extended coagulopathy.

Heparin-induced thrombocytopenia in solid organ transplant recipients: The current scientific knowledge

“…Respective considerations on HIT prevention have been published in several case reports [27][28][29][30][31][32][33][34][35] and are explicitly discussed in the guidelines published by both the American College of Physicians (ACCP) [12] and the British Society of Hematology [36] . In prospective studies a relevant discrepancy was observed between detection of anti-PF4/heparin antibodies (EIA positive: 27%-50% of the patients) and the capability of these antibodies to activate platelets (SRA or HIPA positive: 7%-40% within the EIA positive patients) [26,37,38] .…”

Development of a fast and simple liquid chromatography–tandem mass spectrometry method for the quantitation of argatroban in patient plasma samples

“…The UPLC-MS/MS method was unaffected by factors such as high fibrinogen which can lead to inaccurate determinations of argatroban concentrations by indirect clotting-based methods. Direct measurement of argatroban using a direct approach may provide a more accurate determination of argatroban levels in certain clinical situations known to increase fibrinogen levels, such as in diabetics, post menopausal women, in persons with a high body mass index, and in smokers [18].…”

“…Because there are no reversal agents for DTIs, elevated levels of these drugs carry the risk of life-threatening bleeding complications [16]. Thus, underestimation of argatroban may exacerbate certain clinical situations and lead to extended coagulopathy [18]. The direct UPLC-MS/MS assay was unaffected by elevated fibrinogen levels and thus, should provide a more accurate determination of argatroban concentrations in patients with abnormally high fibrinogen levels (Fig.…”

Anticoagulant Managements of Left Ventricular Assist Device Implantation in Two Patients with Heparin-Induced Thrombocytopenia (HIT): Use of Argatroban as an Anticoagulant for Cardiopulmonary Bypass

“…The liver metabolizes argatroban. Genzen and colleagues reported that a cardiac transplant patient with a suspected history of HIT had excessive anticoagulation and blood loss in the perioperative period when argatroban was used because the prolonged elevation of argatroban concentration after infusion may have been influenced by the patient's critical condition, cardiac output, and decreased postoperative hepatic function [8]. Therefore, in our patients, the anticoagulation effect of argatroban was prolonged, probably because of liver dysfunction accompanied by right-sided heart failure, leading to abnormality in haemostasis.…”