P0229 / #671: USE OF DIRECT THROMBIN INHIBITORS (DTI’S) FOR ANTICOAGULATION IN PEDIATRIC EXTRACORPOREAL MEMBRANE OXYGENATION (ECMO)

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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Argatroban anticoagulation for adult Extracorporeal Membrane Oxygenation: A systematic review

10.21203/rs.3.rs-52236/v1 ◽

2020 ◽

Author(s):

Janos Geli ◽

Massimo Capoccia ◽

Dirk M Maybauer ◽

Marc O Maybauer

Keyword(s):

Extracorporeal Membrane Oxygenation ◽

Life Support ◽

Case Reports ◽

Case Series ◽

Thrombin Inhibitors ◽

Target Range ◽

Circulatory Support ◽

Direct Thrombin Inhibitors ◽

Complication Rates ◽

Membrane Oxygenation

Abstract Background: Extracorporeal Membrane Oxygenation (ECMO) is an established method of circulatory support in critically ill patients. Heparin is the widely used anti-coagulation treatment for patients on ECMO in view of its features. Nevertheless, heparin-induced thrombocytopenia (HIT) and acquired anti-thrombin III (AT-III) deficiency may lead to sub-therapeutic anticoagulation with potentially serious consequences. Direct thrombin inhibitors are being proposed as potential alternatives with argatroban and bivalirudin as main agents. We aimed to review the evidence supporting the effectiveness and safety 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 18th 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 Extra Corporeal Life Support (ECLS) was n = 317. 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 to 60-100 seconds for aPTT and 150-210 to 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 safe and viable alternative to UFH in patients requiring ECLS. To establish an ideal dosing strategy, larger prospective studies on well-defined patient populations are warranted.

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Argatroban versus heparin in patients without heparin-induced thrombocytopenia during venovenous extracorporeal membrane oxygenation: a propensity-score matched study

Critical Care ◽

10.1186/s13054-021-03581-x ◽

2021 ◽

Vol 25 (1) ◽

Author(s):

Christoph Fisser ◽

Maren Winkler ◽

Maximilian V. Malfertheiner ◽

Alois Philipp ◽

Maik Foltan ◽

...

Keyword(s):

Propensity Score ◽

Extracorporeal Membrane Oxygenation ◽

Major Bleeding ◽

University Hospital ◽

Thrombin Inhibitors ◽

Direct Thrombin Inhibitors ◽

Heparin Induced Thrombocytopenia ◽

Membrane Oxygenation ◽

Technical Complications ◽

Venovenous Extracorporeal Membrane Oxygenation

Abstract Background During venovenous extracorporeal membrane oxygenation (vvECMO), direct thrombin inhibitors are considered by some potentially advantageous over unfractionated heparin (UFH). We tested the hypothesis that Argatroban is non-inferior to UFH regarding thrombosis and bleeding during vvECMO. Methods We conducted a propensity-score matched observational non-inferiority study of consecutive patients without heparin-induced-thrombocytopenia (HIT) on vvECMO, treated between January 2006 and March 2019 in the medical intensive care unit at the University Hospital Regensburg. Anticoagulation was realized with UFH until August 2017 and with Argatroban from September 2017 onwards. Target activated partial thromboplastin time was 50 ± 5seconds in both groups. Primary composite endpoint was major thrombosis and/or major bleeding. Major bleeding was defined as a drop in hemoglobin of ≥ 2 g/dl/day or in transfusion of ≥ 2 packed red cells/24 h, or retroperitoneal, cerebral, or pulmonary bleeding. Major thrombosis was defined as obstruction of > 50% of the vessel lumen diameter by means of duplex sonography. We also assessed technical complications such as oxygenator defects or pump head thrombosis, the time-course of platelets, and the cost of anticoagulation (including HIT-testing). Results Out of 465 patients receiving UFH, 78 were matched to 39 patients receiving Argatroban. The primary endpoint occurred in 79% of patients in the Argatroban group and in 83% in the UFH group (non-inferiority for Argatroban, p = 0.026). The occurrence of technical complications was equally distributed (Argatroban 49% vs. UFH 42%, p = 0.511). The number of platelets was similar in both groups before ECMO therapy but lower in the UFH group after end of ECMO support (median [IQR]: 141 [104;198]/nl vs. 107 [54;171]/nl, p = 0.010). Anticoagulation costs per day of ECMO were higher in the Argatroban group (€26 [13.8;53.0] vs. €0.9 [0.5;1.5], p < 0.001) but not after accounting for blood products and HIT-testing (€63 [42;171) vs. €40 [17;158], p = 0.074). Conclusion In patients without HIT on vvECMO, Argatroban was non-inferior to UFH regarding bleeding and thrombosis. The occurrence of technical complications was similarly distributed. Argatroban may have less impact on platelet decrease during ECMO, but this finding needs further evaluation. Direct drug costs were higher for Argatroban but comparable to UFH after accounting for HIT-testing and transfusions.

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