Cerebral infarction following administration of andexanet alfa for anticoagulant reversal in a patient with traumatic acute subdural hematoma
- Department of Neurosurgery, Sendai City Hospital, Sendai, Miyagi, Japan.
- Department of Neurosurgery, Isinomaki Red Cross Hospital, Ishinomaki, Japan.
- Department of Neurosurgery, Tohoku University Graduate School of Medicine, Sendai, Miyagi, Japan.
Arata Nagai, Department of Neurosurgery, Sendai City Hospital, Sendai, Miyagi, Japan.
DOI:10.25259/SNI_358_2023Copyright: © 2023 Surgical Neurology International This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-Share Alike 4.0 License, which allows others to remix, transform, and build upon the work non-commercially, as long as the author is credited and the new creations are licensed under the identical terms.
How to cite this article: Arata Nagai1, Hiroshi Karibe1, Ayumi Narisawa1, Motonobu Kameyama1, Shuichi Ishikawa2, Naoya Iwabuchi2, Teiji Tominaga3. Cerebral infarction following administration of andexanet alfa for anticoagulant reversal in a patient with traumatic acute subdural hematoma. 11-Aug-2023;14:286
How to cite this URL: Arata Nagai1, Hiroshi Karibe1, Ayumi Narisawa1, Motonobu Kameyama1, Shuichi Ishikawa2, Naoya Iwabuchi2, Teiji Tominaga3. Cerebral infarction following administration of andexanet alfa for anticoagulant reversal in a patient with traumatic acute subdural hematoma. 11-Aug-2023;14:286. Available from: https://surgicalneurologyint.com/surgicalint-articles/12494/
Background: Anticoagulants prevent thrombosis in patients with atrial fibrillation (AF) and venous thromboembolism but increase the risk of hemorrhagic complications. If severe bleeding occurs with anticoagulant use, discontinuation and rapid reversal are essential. However, the optimal timing for resuming anticoagulants after using reversal agents remains unclear. Here, we report early cerebral infarction following the use of andexanet alfa (AA), a specific reversal agent for factor Xa inhibitors, in a patient with traumatic acute subdural hematoma (ASDH). The possible causes of thromboembolic complication and the optimal timing for anticoagulant resumption are discussed.
Case Description: An 84-year-old woman receiving rivaroxaban for AF presented with impaired consciousness after a head injury. Computed tomography (CT) revealed right ASDH. The patient was administered AA and underwent craniotomy. Although the hematoma was entirely removed, she developed multiple cerebral infarctions 10 h after the surgery. These infarctions were considered cardiogenic cerebral embolisms and rivaroxaban was therefore resumed on the same day. This case indicates the possibility of early cerebral infarction after using a specific reversal agent for factor Xa inhibitors.
Conclusion: Most studies suggest that the safest time for resuming anticoagulants after using reversal agents is between 7 and 12 days. The present case showed that embolic complications may develop much earlier than expected. Early readministration of anticoagulant may allow for adequate prevention of the acute thrombotic syndromes.
Keywords: Acute subdural hematoma, Andexanet alfa, Anticoagulant, Cerebral infarction
Direct oral anticoagulants (DOAC), including factor Xa inhibitors, reduce the incidence of thromboembolic events in patients with atrial fibrillation (AF) or venous thromboembolism.[
While the efficacy of such reversal agents is being established, the timing of anticoagulant therapy resumption remains controversial. After reversal of anticoagulant therapy, the risk of thromboembolic events increases with delays in anticoagulant resumption. Clinicians must make the difficult decision regarding when to resume anticoagulants.
Anticoagulant-associated traumatic acute subdural hematoma (ASDH) is a devastating injury with high morbidity and mortality.[
In this report, we present a case of traumatic ASDH during anticoagulation therapy that resulted in early cerebral infarction after AA administration. We also discuss the timing of anticoagulant resumption in patients with traumatic ASDH who received anticoagulant reversal agents. The study participant provided informed consent and the study design was approved by the appropriate Ethics Review Board.
An 84-year-old woman with a medical history of AF, hypertension, diabetes mellitus, and cerebral infarction and who was receiving rivaroxaban (15 mg/day) experienced frequent falls in her residential facility due to delirium. She then developed a consciousness disorder on awakening. She was transferred to our hospital with a diagnosis of the right ASDH [
Neuroradiological findings of the case. (a) Plain computed tomography (CT) taken at admission showing a right-sided acute subdural hematoma with low-density areas in some places. (b) CT immediately after surgery showing total subdural hematoma removal and effective intracranial decompression. (c and d) Magnetic resonance imaging taken the day after surgery showing multiple acute cerebral infarctions in the bilateral cerebellar hemispheres, corpus callosum, and cerebral cortex. (e and f) Magnetic resonance angiography showed no vascular abnormalities such as cerebral vascular stenosis, occlusion, or vasospasm.
Anticoagulant therapy is effective in preventing ischemic disease in patients with AF, mechanical cardiac valve replacement, or deep venous thrombosis. In contrast, it increases the risk of poor outcomes in patients with traumatic ASDH, mainly resulting from the size or delayed enlargement of the hematoma.[
On the other hand, discontinuation and/or reversal of anticoagulants may increase the risk of thromboembolic complications. In the present case, cardiogenic embolic infarctions occurred within a day after reversal of anticoagulation with AA. The mechanism of thromboembolic complications may be related to the following factors: (1) characteristics of the reversal agent itself, (2) underlying personal health condition, and (3) pathogenesis of the hemorrhage.
Thromboembolic risk related to characteristics of the reversal agent
It is believed that AA does not exert procoagulant effects. It is unable to cleave prothrombin into thrombin because the serine in the active site is replaced by alanine.[
Thromboembolic risk related to underlying disease
The risk of thromboembolic complications may be different in each patient depending on the underlying disease for which anticoagulation is introduced. It is suggested that anticoagulants should be resumed earlier than previously thought, approximately 3 days after medical presentation.[
Thromboembolic risk related to the pathogenesis of the hemorrhage
The patient had sustained traumatic ASDH. The coagulation/ fibrinolytic system may be abnormal in traumatic hemorrhage compared with nontraumatic hemorrhage, resulting in postoperative hypercoagulability.[
PTCI of the occipital lobe is well described and often results from compression of the posterior cerebral artery against the tentorium by the herniating medial temporal lobe. Middle cerebral artery territory infarcts may occur as a result of displacement from mass lesions and herniation as well. Cerebral infarction in this case did not depend on the area of vascular control; the multiple small infarcts suggest a cause other than cerebral herniation. Other mechanisms may include vasospasm or thromboembolic events from injured carotid and vertebral arteries. However, magnetic resonance angiography demonstrated no concomitant vascular injury in this patient. Based on the above, the discontinuation of anticoagulants and use of the reversal agent were likely involved in the embolism in this case.
Appropriate time to resume anticoagulants
It appears safe to discontinue anticoagulation for brief periods in nontraumatic anticoagulant-related cerebral hemorrhage.[
Three of the reports summarized in
There have been some reports of heparin initiation in the hyperacute phase within 24 h after injury for deep vein thrombosis prevention.[
As observed in the present case, cerebral infarction sometimes occurs early after reversal agent use. A meta-analysis of taking anticoagulants showed all thromboembolic complication occurred within a few days (1–4 days) of reversal agent administration.[
AA was used as an effective reversal agent to achieve hemostasis in a patient with traumatic ASDH. The patient had thromboembolic events, and it cannot be ruled out that AA may have been a contributing factor to their occurrence. In patients with traumatic ASDH treated with AA, early anticoagulant resumption may need to be considered because of the higher embolization risk. More real-world studies on AA use, including the timing of anticoagulant resumption, will greatly add to our knowledge and comfort in using this important drug.
The authors certify that they have obtained all appropriate patient consent.
There are no conflicts of interest.
The views and opinions expressed in this article are those of the authors and do not necessarily reflect the official policy or position of the Journal or its management. The information contained in this article should not be considered to be medical advice; patients should consult their own physicians for advice as to their specific medical needs.
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