Argatroban for Anticoagulation in Patients Requiring Venovenous Extracorporeal Membrane Oxygenation in Coronavirus Disease 2019

Abstract

OBJECTIVES: A significant proportion of patients with coronavirus disease 2019 requiring venovenous extracorporeal membrane oxygenation at our institution demonstrated heparin resistance, which in combination with a heparin shortage resulted in the transition to argatroban with or without aspirin as an alternative anticoagulation strategy. The optimal anticoagulation strategy for coronavirus disease 2019 patients requiring venovenous extracorporeal membrane oxygenation is unknown, and therefore, we sought to evaluate the efficacy and safety of argatroban with or without aspirin as an alternative anticoagulation strategy in this patient population. DESIGN: Retrospective cohort. SETTING: Single-center tertiary-care facility in Fort Sam Houston, TX, from 2020 to 2021. PATIENTS: Twenty-four patients who were cannulated for venovenous extracorporeal membrane oxygenation due to respiratory failure secondary to coronavirus disease 2019. INTERVENTIONS: Argatroban, with or without aspirin, was substituted for heparin in coronavirus disease 2019 patients requiring venovenous extracorporeal membrane oxygenation. MEASUREMENTS AND MAIN RESULTS: Eighty percent of our coronavirus disease 2019 patients requiring venovenous extracorporeal membrane oxygenation demonstrated heparin resistance, and patients who were initially started on heparin were significantly more likely to require a change to argatroban than vice versa due to difficulty achieving or maintaining therapeutic anticoagulation goals (93.4% vs 11.1%; p < 0.0001). The time to reach the therapeutic anticoagulation goal was significantly longer for patients who were initially started on heparin in comparison with argatroban (24 vs 6 hr; p = 0.0173). Bleeding and thrombotic complications were not significantly different between the two cohorts. CONCLUSIONS: Argatroban, with or without aspirin, is an effective anticoagulation strategy for patients who require venovenous extracorporeal membrane oxygenation support secondary to coronavirus disease 2019. In comparison with heparin, this anticoagulation strategy was not associated with a significant difference in bleeding or thrombotic complications, and was associated with a significantly decreased time to therapeutic anticoagulation goal, likely as a result of high rates of heparin resistance observed in this patient population.

Variation in outcomes with extracorporeal membrane oxygenation in the era of coronavirus: A multicenter cohort evaluation

“… 41 A similar single-center study found that the use of argatroban resulted in a quicker attainment of therapeutic anticoagulation than unfractionated heparin, but there were no differences in bleeding or thrombotic complications between anticoagulants. 42 While the present study did show a preferential use of DTI (bivalirudin or argatroban) for COVID-19 patients (37.5% use vs 12.0% and 5.8% for both the pulmonary and cardiac groups respectively), circuit complications and thrombus were still found more frequently during ECMO when they were used. This differs from the previous study that showed fewer overall complications, and may reflect the virulent nature of COVID-19 on obviating any benefit of alternative coagulation regimens.…”

Direct Thrombin Inhibition in Extracorporeal Membrane Oxygenation

“…This represents an advantage in the setting of V-A ECMO compared to bivalirudin, which has a shorter half-life (25 min) thus increased risk of clot formation in areas of blood flow stagnation. Compared to UFH, no significant differences were seen in patient 3,7,19 or circuit-related 19 thromboembolic complications.…”

“…Heparin resistance is common among Covid-19 patients on ECMO support, and the use of DTIs may be of significant benefit in this patient population. 3 A substantial number of COVID-19 patients require ECMO as a rescue modality. This group is known to have increased incidence of patient and ECMO system-related thromboembolic complications.…”

“…ACT is less commonly utilized with targets ranging from 150–210 s to 180–230 s. 7 Several observations support shorter time to reach the therapeutic anticoagulation target with argatroban compared to UFH. 3,7 Some data suggest that during the first days of argatroban initiation more frequent dose adjustments may be needed compared to UFH. 7 This, however, stabilizes after the first 2 days.…”

“…Most studies reported no increased hemorrhagic risk in argatroban versus UFH anticoagulated patients on ECMO 3,7,19 Although some studies observed higher rates of bleeding for argatroban, this usually occurred in the perioperative period or in patients with HIT and associated thrombocytopenia. 7 Although argatroban has no specific reversal agents, reversal of argatroban-related severe bleeding by recombinant factor VII has been described.…”