Intraoperative Unfractionated Heparin Unresponsiveness during Endovascular Repair of a Ruptured Abdominal Aortic Aneurysm following Administration of Andexanet Alfa for the Reversal of Rivaroxaban

Abstract

The authors describe a case of unfractionated heparin (UFH) unresponsiveness in the operating room secondary to reversal of rivaroxaban with coagulation factor Xa (recombinant) inactivated-zhzo (andexanet alfa). A 70-year-old man with a known 4.5-to 5.0-cm abdominal aortic aneurysm and atrial fibrillation managed with rivaroxaban presented with severe right-sided flank pain radiating to the left side of his abdomen. Computed tomography-angiography on arrival demonstrated a left retroperitoneal hematoma and a suspected ruptured abdominal aortic aneurysm. He received andexanet alfa to reverse rivaroxaban prior to an emergent endovascular aneurysm repair. During surgery, he received a total of 14,000 units (167 units/kg) of UFH with minimal changes in activated clotting time (132-144 sec; baseline 135 sec [reference range 74-137 sec]). This case highlights the potential complications of using UFH anticoagulation following reversal of factor Xa inhibitors with andexanet alfa and underscores the importance of peri-procedural anticoagulation planning. For patients who require intra-operative anticoagulation, providers should consider anticoagulation reversal with prothrombin complex concentrate instead of andexanet alfa or administration of a parenteral direct thrombin inhibitor, such as argatroban or bivalirudin during the surgical procedure. KEY WORDS andexanet alfa, factor Xa reversal, direct oral anticoagulants, unfractionated heparin unresponsiveness, rivaroxaban, abdominal aortic aneurysm, endovascular repair, endovascular aneurysm repair.

Andexanet Alfa–Induced Heparin Resistance: When Anticoagulation Really Remains Reversed

“…shortly after administration of andexanet alfa in patients requiring heparin anticoagulation for emergency vascular surgery. 2,3 These reports are in line with recent in-vitro investigations showing that the effect of UFH on the activated clotting time (ACT) and R-time in thromboelastography is reversed by addition of andexanet alfa. 4 Although it is obvious that andexanet alfa should not be administered prior to cardiac surgery, 5 it is conceivable that it could be necessary in emergency situations requiring fast institution or reinstitution of cardiopulmonary bypass (CPB).…”

“…Andexanet alfa was approved by the US Food and Drug Administration in 2018 through its Accelerated Approval Program. 12 However, the clinical studies were rather limited in scope and in the patient populations enrolled, 3 and it appears that the potential for collateral damage in other areas was never adequately considered. Given that patients with atrial fibrillation are often at cardiovascular risk, the situations reported here should have been anticipated.…”

Difficult Intraoperative Heparinization Following Andexanet Alfa Administration

“…He sustained thrombosis of his pelvic vasculature without any clinical adverse consequences. This case is highly clinically relevant given the novelty of both the agent and the intraoperative complications at hand; in fact, this case is being published within the clinical pharmacy literature as well with a focus on the pharmacology of the heparin-AnXa interaction and the valuable role of pharmacists in making decisions regarding reversal of anticoagulation 17…”

Successful Antithrombin Administration in Andexanet Alfa-Associated Heparin Resistance

“…In another case report, Eche et al described an altered heparin response following the administration of andexanet alfa in a patient who presented for urgent endovascular repair of a ruptured abdominal aortic aneurysm (9). The authors were unable to achieve adequate anticoagulation intraoperatively despite the administration of a supratherapeutic dose of UFH.…”