Bivalirudin for Maintenance Anticoagulation During Venovenous Extracorporeal Membrane Oxygenation for COVID-19.

In its severe manifestation, coronavirus disease 2019 (COVID-19) compromises oxygenation in a manner that is refractory to maximal conventional support and requires escalation to extracorporeal membrane oxygenation (ECMO). Maintaining ECMO support for extended durations requires a delicately balanced anticoagulation strategy to maintain circuit viability by preventing thrombus deposition while avoiding excessive anticoagulation yielding hemorrhage-a task that is complicated in COVID-19 secondary to an inherent hypercoagulable state. Bivalirudin, a member of the direct thrombin inhibitor drug class, offers potential advantages during ECMO, including to its ability to exert its effect by directly attaching to and inhibiting freely circulating and fibrin-bound thrombin. Herein, the successful use of an anticoagulation strategy using the off-label use of a continuous infusion of bivalirudin in a case of severe hypoxemic and hypercarbic respiratory failure caused by COVID-19 requiring venovenous ECMO is reported. Importantly, therapeutic anticoagulation intensity was achieved rapidly with stable pharmacokinetics, and there was no need for any circuit interventions throughout the patient's 27-day ECMO course. In COVID-19, bivalirudin offers a potential option for maintaining systemic anticoagulation during ECMO in a manner that may mitigate the prothrombotic nature of the underlying pathophysiologic state.

Seelhammer TG ，Rowse P ，Yalamuri S 《-》

Comparison of Anticoagulation Strategies in Patients Requiring Venovenous Extracorporeal Membrane Oxygenation: Heparin Versus Bivalirudin.

Extracorporeal membrane oxygenation is a life-sustaining therapy for severe respiratory failure. Extracorporeal membrane oxygenation circuits require systemic anticoagulation that creates a delicate balance between circuit-related thrombosis and bleeding-related complications. Although unfractionated heparin is most widely used anticoagulant, alternative agents such as bivalirudin have been used. We sought to compare extracorporeal membrane oxygenation circuit thrombosis and bleeding-related outcomes in respiratory failure patients receiving either unfractionated heparin or bivalirudin for anticoagulation on venovenous extracorporeal membrane oxygenation support. Retrospective cohort study. Single-center, cardiothoracic ICU. Consecutive patients requiring venovenous extracorporeal membrane oxygenation who were maintained on anticoagulation between 2013 and 2020. IV bivalirudin or IV unfractionated heparin. Primary outcomes were the presence of extracorporeal membrane oxygenation in-circuit-related thrombotic complications and volume of blood products administered during extracorporeal membrane oxygenation duration. One hundred sixty-two patients receiving unfractionated heparin were compared with 133 patients receiving bivalirudin for anticoagulation on venovenous extracorporeal membrane oxygenation. In patients receiving bivalirudin, there was an overall decrease in the number of extracorporeal membrane oxygenation circuit thrombotic complications (p < 0.005) and a significant increase in time to circuit thrombosis (p = 0.007). Multivariable Cox regression found that heparin was associated with a significant increase in risk of clots (Exp[B] = 2.31, p = 0.001). Patients who received bivalirudin received significantly less volume of packed RBCs, fresh frozen plasma, and platelet transfusion (p < 0.001 for each). There was a significant decrease in the number major bleeding events in patients receiving bivalirudin, 40.7% versus 11.7%, p < 0.001. Patients receiving bivalirudin for systemic anticoagulation on venovenous extracorporeal membrane oxygenation experienced a decrease in the number of extracorporeal membrane oxygenation circuit-related thrombotic events as well as a significant decrease in volume of blood products administered.

Rivosecchi RM ，Arakelians AR ，Ryan J ，Murray H ，Ramanan R ，Gomez H ，Phillips D ，Sciortino C ，Arlia P ，Freeman D ，Sappington PL ，Sanchez PG ... -  《-》

Bivalirudin for Alternative Anticoagulation in Extracorporeal Membrane Oxygenation: A Systematic Review.

Sanfilippo F ，Asmussen S ，Maybauer DM ，Santonocito C ，Fraser JF ，Erdoes G ，Maybauer MO ... -  《-》

Bivalirudin versus heparin as an anticoagulant during extracorporeal membrane oxygenation: a case-control study.

Heparin-based anticoagulation for patients undergoing extracorporeal membrane oxygenation has many limitations, including a high risk of heparin-induced thrombocytopenia. However, little experience with other anticoagulants in these patients has been described. The aim of this study was to compare bivalirudin-based anticoagulation with heparin-based protocols in a population of patients treated with venovenous or venoarterial extracorporeal membrane oxygenation. In this case-control study, 10 patients received bivalirudin (cases) and 10 heparin (controls). The target activated partial thromboplastin time (aPTT) was 45 to 60 seconds. None. aPTT variations >20% of the previous value were much more frequent in patients treated with heparin than in patients receiving bivalirudin (52 v 24, p < 0.001). The number of corrections of the anticoagulant dose was higher in the heparin group compared with the bivalirudin group (58 v 51), although it did not reach statistical significance. Bleeding, thromboembolic complications, extracorporeal membrane oxygenation (ECMO) support duration, mortality, and the number of episodes of aPTT >80 seconds were not different between the 2 groups. A further analysis was performed in the bivalirudin group according to the presence of acute renal failure requiring continuous venovenous hemofiltration. The median bivalirudin dose in patients with or without hemofiltration was 0.041 (0.028-0.05) mg/kg/h and 0.028 (0-0.041) mg/kg/h, respectively (p = 0.2). Bivalirudin-based anticoagulation may represent a new method of anticoagulation for reducing thromboembolic and bleeding complications, which still jeopardize the application of extracorporeal membrane oxygenation. Moreover, bivalirudin is free from the risk of heparin-induced thrombocytopenia. Higher doses of bivalirudin may be needed in patients undergoing hemofiltration.

Pieri M ，Agracheva N ，Bonaveglio E ，Greco T ，De Bonis M ，Covello RD ，Zangrillo A ，Pappalardo F ... -  《-》

Anticoagulation Management in Severe Coronavirus Disease 2019 Patients on Extracorporeal Membrane Oxygenation.

To explore special coagulation characteristics and anticoagulation management in extracorporeal membrane oxygenation (ECMO)-assisted patients with coronavirus disease 2019 (COVID-19). Single-center, retrospective observation of a series of patients. Laboratory-confirmed severe COVID-19 patients who received venovenous ECMO support from January 20-May 20, 2020. This study analyzed the anticoagulation management and monitoring strategies, bleeding complications, and thrombotic events during ECMO support. Eight of 667 confirmed COVID-19 patients received venovenous ECMO and had an elevated D-dimer level before and during ECMO support. An ECMO circuit pack (oxygenator and tubing) was replaced a total of 13 times in all 8 patients, and coagulation-related complications included oxygenator thrombosis (7/8), tracheal hemorrhage (5/8), oronasal hemorrhage (3/8), thoracic hemorrhage (3/8), bleeding at puncture sites (4/8), and cannulation site hemorrhage (2/8). Hypercoagulability and secondary hyperfibrinolysis during ECMO support in COVID-19 patients are common and possibly increase the propensity for thrombotic events and failure of the oxygenator. Currently, there is not enough evidence to support a more aggressive anticoagulation strategy.

Guo Z ，Sun L ，Li B ，Tian R ，Zhang X ，Zhang Z ，Clifford SP ，Liu Y ，Huang J ，Li X ... -  《-》