Anticoagulation with direct thrombin inhibitors during extracorporeal membrane oxygenation

Burstein, Barry; Wieruszewski, Patrick M.; Zhao, Yanjun; Smischney, Nathan J.

doi:10.5492/wjccm.v8.i6.87

Cited by 51 publications

(73 citation statements)

References 51 publications

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“…Patients on V-A ECMO are more likely to experience severe thrombocytopenia and arterial thromboembolism; those on V-V ECMO are more likely to require device or circuit exchange due to oxygenator thromboembolism [32]. Direct thrombin inhibitors (DTIs) have received signi cant attention in recent years with preference towards argatroban and bivalirudin [11,12,33]. Bivalirudin has a half life of approximately 25 minutes, which may be a limitation in areas of blood stagnation, especially during V-A ECMO with non-pulsatile ow [34].…”

Section: Discussionmentioning

confidence: 99%

Argatroban Anticoagulation for Adult Extracorporeal Membrane Oxygenation: A Systematic Review

Geli

Capoccia

Maybauer

et al. 2021

J Intensive Care Med

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Background: Heparin is the widely used anti-coagulation strategy for patients on extracorporeal membrane oxygenation (ECMO). Nevertheless, heparin-induced thrombocytopenia (HIT) and acquired anti-thrombin (AT) deficiency preclude the use of heparin requiring utilization of an alternative anticoagulant agent. Direct thrombin inhibitors are being proposed as potential alternatives with argatroban as one of the main agents. We aimed to review the evidence with regard to safety and efficacy of argatroban as a potential definitive alternative to heparin in the adult patient population undergoing ECMO support. Methods: A web-based systematic literature search was performed in Medline (PubMed) and Embase from inception until June 18, 2020. Results: The search identified 13 publications relevant to the target (4 cohort studies and 9 case series). Case reports and case series with less than 3 cases were not included in the qualitative synthesis. The aggregate number of argatroban treated patients on ECMO was n = 307. In the majority of studies argatroban was used as a continuous infusion without loading dose. Starting doses on ECMO varied between 0.05 and 2 μg/kg/min and were titrated to achieve the chosen therapeutic target range. The activated partial thormboplastin time (aPTT) was the anticoagulation parameter used for monitoring purposes in most studies, whereas some utilized the activated clotting time (ACT). Optimal therapeutic targets varied between 43-70 and 60-100 seconds for aPTT and between 150-210 and 180-230 seconds for ACT. Bleeding and thromboembolic complication rates were comparable to patients treated with unfractionated heparin (UFH). Conclusions: Argatroban infusion rates and anticoagulation target ranges showed substantial variations. The rational for divergent dosing and monitoring approaches are discussed in this paper. Argatroban appears to be a potential alternative to UFH in patients requiring ECMO. To definitively establish its safety, efficacy and ideal dosing strategy, larger prospective studies on well-defined patient populations are warranted.

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Section: Discussionmentioning

confidence: 99%

Argatroban Anticoagulation for Adult Extracorporeal Membrane Oxygenation: A Systematic Review

Geli

Capoccia

Maybauer

et al. 2021

J Intensive Care Med

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“…This literature review revealed five studies, four of them concerning DTIs. DTIs have advantages over UFH, including direct binding of both circulating and clot-bound thrombin, resulting in increased efficacy compared to UFH, antithrombin independence and no risk of heparin-induced thrombocytopenia (41). Bivalirudin is the most commonly used alternative for UFH in pediatric patients.…”

Section: Discussionmentioning

confidence: 99%

Challenges in Maintaining the Hemostatic Balance in Children Undergoing Extracorporeal Membrane Oxygenation: A Systematic Literature Review

et al. 2020

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Background: Despite advances in technology and clinical experience, the incidence of hemostatic complications, including bleeding and thrombosis, remains high in children supported with extracorporeal membrane oxygenation (ECMO). These hemostatic complications are important to prevent, since they are associated with increased morbidity and mortality. This systematic literature review aims to outline the most important risk factors for hemostatic complications in children undergoing ECMO treatment, to summarize the reported alternative anticoagulant drugs used in pediatric ECMO and to describe studied associations between coagulation tests and hemostatic complications.Methods: A literature search was performed in Embase, Medline, Web of Science Core Collection, Cochrane Central Register of Controlled Trials, and Google Scholar in February 2020. Included studies were studies evaluating children (<18 years old) treated with ECMO, and studies evaluating risk factors for hemostatic complications, alternative anticoagulants, or the association between coagulation tests and hemostatic complications.Results: Out of 1,152 articles, 35 studies were included. Thirteen out of 49 risk factors were investigated in three or more studies. Most consistent results were found regarding ECMO duration and pH. However, evidence for risk factors was equivocal in the majority of studies, which is explained by the variability of populations studied, definitions of hemostatic complications, ECMO circuits, anticoagulation protocols, transfusion triggers and monitoring of anticoagulation. Five studies described alternative anticoagulants, including bivalirudin (n = 3), argatroban (n = 1) and FUT (n = 1). Higher anti-factor Xa levels were associated with less clotting events in one of nine studies, investigating the association between tests and hemostatic complications. Two studies revealed an association between anti-factor Xa assay-based protocols and a decreased number of transfusions, bleedings and need for circuit change.Conclusion: Studies regarding risk factors showed conflicting results and a few retrospective studies reported the use of new anticoagulants and data on coagulation tests in relation to hemostatic complications. To decrease hemostatic complications in ECMO children, prospective multicenter studies are needed with clear bleeding and thrombotic definitions, and the best possible standardization of ECMO circuits used, anticoagulation protocols, and transfusion triggers.

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“…Because of its largely organ-independent metabolism, bivalirudin has a short half-life of 25 minutes in patients with normal renal function. 6,18 Other reported benefits of this drug class, when compared with heparin, include the ability to inhibit circulating and clot-bound thrombin and the absence of association with HIT. 18 Sepsis and acute respiratory distress syndrome, including COVID-19, are characterized by a procoagulant state that results in a massive production of thrombin.…”

Section: Discussionmentioning

confidence: 99%

“…6,18 Other reported benefits of this drug class, when compared with heparin, include the ability to inhibit circulating and clot-bound thrombin and the absence of association with HIT. 18 Sepsis and acute respiratory distress syndrome, including COVID-19, are characterized by a procoagulant state that results in a massive production of thrombin. 19 In addition to direct effects on the endothelial barrier by thrombin, the subsequent cleavage of fibrinogen to fibrin results in diffuse alveolar and interstitial fibrin deposition yielding the formation of microthrombi.…”

Section: Discussionmentioning

confidence: 99%

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

Seelhammer

Rowse

Yalamuri

2021

Journal of Cardiothoracic and Vascular Anesthesia

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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.

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Anticoagulation with direct thrombin inhibitors during extracorporeal membrane oxygenation

Cited by 51 publications

References 51 publications

Argatroban Anticoagulation for Adult Extracorporeal Membrane Oxygenation: A Systematic Review

Argatroban Anticoagulation for Adult Extracorporeal Membrane Oxygenation: A Systematic Review

Challenges in Maintaining the Hemostatic Balance in Children Undergoing Extracorporeal Membrane Oxygenation: A Systematic Literature Review

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

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