Heparin Insensitivity and Thrombotic Risk Associated With Sequential Uses of Prothrombin Complex Concentrate and Andexanet Alfa for Apixaban Reversal During Acute Type A Aortic Dissection Repair: A Case Report

Brenner, Brian; Guerra, Jessica; Williams, Carole; Littlewood, Keith E.; Kern, John A.; Tanaka, Kenichi A.; McNeil, John S.; Mangunta, Venkat

doi:10.1213/xaa.0000000000001636

Cited by 13 publications

(4 citation statements)

References 12 publications

(18 reference statements)

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“…The following terms were used to search for relevant records: "andexanet alfa, " "heparin resistance, " "cardiopulmonary bypass, " and "cardiovascular surgery. " We finally detected nine cases of heparin resistance due to andexanet alfa, and those nine cases (in eight articles) were published as journal articles [7,9,[12][13][14][15][16][17]. Table 2 summarizes the characteristics of andexanet alpha-induced heparin resistance in 10 cases, including nine cases from the previous reports described above and one case from the present case report.…”

Section: Discussionmentioning

confidence: 84%

Andexanet alpha-induced heparin resistance treated by nafamostat mesylate in a patient undergoing total aortic arch repair for Stanford type A acute aortic dissection: a case report

Suzuki,

Kikura,

Kawashima

et al. 2024

JA Clin Rep

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Background Andexanet alfa, an anti-Xa inhibitor antagonist, induces heparin resistance. Here, we report a case of successful management of cardiopulmonary bypass with andexanet alfa-induced heparin resistance using nafamostat mesylate. Case presentation An 84-year-old female, with Stanford type A acute aortic dissection, underwent an emergency surgery for total aortic arch replacement. Andexanet alfa 400 mg was administered preoperatively to antagonize edoxaban, an oral Xa inhibitor. Heparin 300 IU/kg was administered before cardiopulmonary bypass, and the activated clotting time (ACT) was 291 s. The ACT was 361 s after another administration of heparin 200 IU/kg. According to our routine therapy for heparin resistance, an initial dose of nafamostat mesylate 10 mg was administered intravenously, followed by a continuous infusion of 20–30 mg/h. The ACT was prolonged to 500 s, and cardiopulmonary bypass was successfully established thereafter. Conclusions This case report presents the successful management of cardiopulmonary bypass with andexanet alfa-induced heparin resistance using nafamostat mesilate. This report presents the successful management of cardiopulmonary bypass with andexanet alfa-induced heparin resistance using nafamostat mesilate.

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Section: Discussionmentioning

confidence: 84%

Andexanet alpha-induced heparin resistance treated by nafamostat mesylate in a patient undergoing total aortic arch repair for Stanford type A acute aortic dissection: a case report

Suzuki,

Kikura,

Kawashima

et al. 2024

JA Clin Rep

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“…Several cases of Andexanet Alfa use in emergency cardiac surgery have been reported. 3,4 The Society of Thoracic Surgeons (STS), in their recent update to the Clinical Practice Guidelines on Patients Blood Management, recommended Andexanet Alfa administration in patients in need of emergent cardiac surgery with recent ingestion of DOAC. 5 Meanwhile, some patients received Andexanet Alfa before CPB showed heparin resistance and experienced CPB circuit thrombosis.…”

Section: Discussionmentioning

confidence: 99%

“…5 Meanwhile, some patients received Andexanet Alfa before CPB showed heparin resistance and experienced CPB circuit thrombosis. 3,4 The mechanism of heparin resistance due to Andexanet Alfa still needs to be fully understood. Prior study has suggested that Andexanet Alfa binds to the antithrombin-heparin complex and causes a lack of heparin-binding antithrombin.…”

Section: Discussionmentioning

confidence: 99%

Effective application of a direct-acting oral anticoagulants reversal agent in acute type A aortic dissection repair: A case report

Wakami,

Fukunaga,

Shimoji

et al. 2024

Asian Cardiovasc Thorac Ann

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There are insufficient reports on the use of andexanet alfa in cardiac surgery. A 67-year-old man was diagnosed with type A aortic dissection and performed emergent surgery. His medical history included atrial fibrillation treated with Edoxaban. We performed total arch replacement. Despite administration of enough protamine, fresh frozen plasma, and platelet administration, controlling bleeding was difficult. Thus, Andexanet Alfa was initiated after CPB withdrawal. Surgical bleeding was dramatically controlled after its administration. There were no findings suggestive of an embolic event. In conclusion, administration of Andexanet Alfa is safe after cardiopulmonary bypass withdrawal.

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“…No clinical trials have reported the efficacy of andexanet alfa in cardiac surgery with CPB, and its clinical use is based on the experience reported in several case reports [4][5][6][7]. These reports often describe heparin resistance following administration of andexanet alfa before CPB, as andexanet alfa also binds to the heparin-antithrombin complex and neutralizes its anticoagulant effect [2].…”

Section: Discussionmentioning

confidence: 99%

Andexanet Alfa for Edoxaban Reversal and Associated Thromboelastography Changes in Surgical Pulmonary Embolectomy

Fukuda,

Yoshinaga,

Kondo

et al. 2024

Cureus

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Andexanet alfa neutralizes factor Xa inhibitors in critical bleeding situations. However, in cardiac surgery with cardiopulmonary bypass (CPB), heparin resistance induced by andexanet alfa should be a concern, and the lack of point-of-care monitoring of plasma concentration of factor Xa inhibitors makes it difficult to decide when to administer andexanet alfa. A 69-year-old man underwent emergency surgery for acute pulmonary thromboembolism. The patient had been on edoxaban until the day before the surgery. Withdrawal from CPB required venoarterial extracorporeal membrane oxygenation due to right heart failure, followed by severe bleeding that required massive transfusion. Despite adequate coagulation factor replacement, bleeding persisted and citrated kaolin-reaction time (CK-R) on thromboelastography (TEG) was prolonged. Administering andexanet alfa achieved excellent hemostasis without any thrombosis and normalized the prolonged CK-R of TEG. This is the first report of a change in TEG findings before and after administration of andexanet alfa in a cardiac surgery patient taking factor Xa inhibitor. Monitoring CK-R in TEG may help evaluate the anticoagulant effect of factor Xa inhibitors and the reversal effect of andexanet alfa.

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Heparin Insensitivity and Thrombotic Risk Associated With Sequential Uses of Prothrombin Complex Concentrate and Andexanet Alfa for Apixaban Reversal During Acute Type A Aortic Dissection Repair: A Case Report

Cited by 13 publications

References 12 publications

Andexanet alpha-induced heparin resistance treated by nafamostat mesylate in a patient undergoing total aortic arch repair for Stanford type A acute aortic dissection: a case report

Andexanet alpha-induced heparin resistance treated by nafamostat mesylate in a patient undergoing total aortic arch repair for Stanford type A acute aortic dissection: a case report

Effective application of a direct-acting oral anticoagulants reversal agent in acute type A aortic dissection repair: A case report

Andexanet Alfa for Edoxaban Reversal and Associated Thromboelastography Changes in Surgical Pulmonary Embolectomy

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