Apixaban [Neurosurgery Wiki]

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====== Apixaban ======

{{rss>https://pubmed.ncbi.nlm.nih.gov/rss/search/1LmeR7JfcIZ8ekn58S1R0JItCGAg1miC8aBSIMCjxYE6GXOUDD/?limit=15&utm_campaign=pubmed-2&fc=20240206065021}}


Apixaban is a [[direct oral anticoagulant]] (DOAC) that belongs to the class of medications known as [[factor Xa inhibitor]]s. It is used for anticoagulation therapy to reduce the risk of blood clots and strokes in certain medical conditions. 

It reversibly blocks the enzymatic function of [[factor Xa]] in converting [[prothrombin]] to [[thrombin]].

===== Apixaban in Neurosurgery =====




If the patient is on apixaban at a prophylactic dose, it should be discontinued 26 to 30 hours before a neuraxial puncture or [[catheter]] placement. May be restarted 4 to 6 hours after the puncture or catheter removal/manipulation.
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The benefit of apixaban over [[aspirin]] for the prevention of recurrent [[cerebral ischemia]] is under current investigation
((Kercher MJ, Ramanathan D, Dahlin BC, Yee AH, Clouse JW, Waldau B. Mechanical Thrombectomy for Sequential Bilateral Middle Cerebral Artery Occlusions in a Patient With Recurrent Cryptogenic Strokes: A Case Report. Neurohospitalist. 2021 Jan;11(1):54-58. doi: 10.1177/1941874420934333. Epub 2020 Jun 25. PMID: 33868558; PMCID: PMC8022181.)).

Currently, conventional [[heparin]] and [[warfarin]] remain first choice [[anticoagulant]]s. If newer anticoagulants are considered, although study numbers are small, at this stage [[Apixaban]] appears to be associated with lesser bleeding risk than [[Rivaroxaban]]
((Shovlin CL, Millar CM, Droege F, Kjeldsen A, Manfredi G, Suppressa P, Ugolini 
S, Coote N, Fialla AD, Geisthoff U, Lenato GM, Mager HJ, Pagella F, Post MC,
Sabbà C, Sure U, Torring PM, Dupuis-Girod S, Buscarini E; VASCERN-HHT. Safety of 
direct oral anticoagulants in patients with hereditary hemorrhagic
telangiectasia. Orphanet J Rare Dis. 2019 Aug 28;14(1):210. doi:
10.1186/s13023-019-1179-1. PubMed PMID: 31462308; PubMed Central PMCID:
PMC6714298.
)).

===== Discontinuation =====

[[Apixaban Discontinuation]].


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Compared with [[warfarin]], the direct [[oral anticoagulant]] apixaban reduces the risk of stroke or systemic embolism, intracranial haemorrhage, and case fatality in patients with atrial fibrillation. Compared with [[aspirin]], apixaban reduces the risk of stroke or systemic embolism in patients with atrial fibrillation, and has a similar risk of intracerebral haemorrhage. Novel oral anticoagulants have not been evaluated in patients with atrial fibrillation and a recent intracerebral haemorrhage. To inform a phase III trial, the phase II Apixaban versus Antiplatelet drugs or no antithrombotic drugs after anticoagulation-associated intraCerebral HaEmorrhage in patients with Atrial Fibrillation (APACHE-AF) trial aims to obtain estimates of the rates of vascular death or non-fatal stroke in patients with atrial fibrillation and a recent anticoagulation-associated intracerebral haemorrhage treated with apixaban and in those in whom oral anticoagulation is avoided.

APACHE-AF is a phase II, multicentre, open-label, parallel-group, randomised clinical trial with masked outcome assessment. One hundred adults with a history of atrial fibrillation and a recent intracerebral haemorrhage during treatment with anticoagulation in whom clinical equipoise exists on the optimal stroke prevention strategy will be enrolled in 14 hospitals in The Netherlands. These patients will be randomly assigned in a 1:1 ratio to either apixaban or to avoiding oral anticoagulation. Patients in the control group may be treated with antiplatelet drugs at the discretion of the treating physician. The primary outcome is the composite of vascular death or non-fatal stroke during follow-up. We aim to include 100 patients in 2.5 years. All patients will be followed-up for the duration of the study, but at least for 1 year. Recruitment commenced in September 2014 and is ongoing. This trial is funded by the Dutch Heart Foundation (2012 T077) and ZonMW (015008048)
((van Nieuwenhuizen KM, van der Worp HB, Algra A, Kappelle LJ, Rinkel GJ, van
Gelder IC, Schutgens RE, Klijn CJ; APACHE-AF Investigators. Apixaban versus
Antiplatelet drugs or no antithrombotic drugs after anticoagulation-associated
intraCerebral HaEmorrhage in patients with Atrial Fibrillation (APACHE-AF): study
protocol for a randomised controlled trial. Trials. 2015 Sep 4;16:393. doi:
10.1186/s13063-015-0898-4. PubMed PMID: 26340977; PubMed Central PMCID:
PMC4560912.
)).
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Prior antiplatelet therapy for large vessel occlusion (LVO) in patients with non-valvular atrial fibrillation (NVAF) newly initiated on apixaban was associated with major bleeding, which was more frequent in the antiplatelet group without [[intravenous thrombolysis]] (IVT).
((Tokuda K, Yamada Y, Uchida K, Sakakibara F, Sakai N, Imamura H, Yamagami H,
Tanaka K, Ezura M, Nonaka T, Matsumoto Y, Shibata M, Ohta H, Morimoto M, Fukawa
N, Hatano T, Enomoto Y, Takeuchi M, Ota T, Shimizu F, Kimura N, Kamiya Y,
Shimamura N, Morimoto T, Yoshimura S. Effect of prior antiplatelet therapy on
large vessel occlusion in patients with non-valvular atrial fibrillation newly
initiated on apixaban. J Neurol Sci. 2021 Sep 15;428:117603. doi:
10.1016/j.jns.2021.117603. Epub 2021 Aug 4. PMID: 34384970.)).

===== Hematoma expansion with Apixaban =====

{{rss>https://pubmed.ncbi.nlm.nih.gov/rss/search/1nGQFE-05Nk35g_0UZd4Dh7RTjzG_ovVvbmC6LSAwCByok4Y9t/?limit=15&utm_campaign=pubmed-2&fc=20240208175447}}

A case report describes a 69-year-old female who initially presented to an emergency department at a community hospital due to a ground-level fall with traumatic intracranial hemorrhage. The patient reportedly ingested apixaban 275 mg, carvedilol 250 mg, atorvastatin 1,200 mg, and unknown amounts of amlodipine and ethanol. Anti-inhibitor coagulant complex, an aPCC, was administered approximately 3 hours after presentation. Initial thromboelastography performed approximately 4 hours after presentation showed a prolonged reaction time of 16.8 minutes. Ongoing imaging and evidence of coagulopathy prompted repeated aPCC administration to a cumulative dose of approximately 100 U/kg. The patient underwent craniotomy with hematoma evacuation. Postoperative imaging showed expansion of the existing intracranial hemorrhage and new areas of hemorrhage. [[Andexanet alfa]] was administered approximately 18 hours after presentation, followed by repeat craniotomy with evacuation of the hematoma. No further expansion of the intracranial hemorrhage was observed, and the reaction time on thromboelastography was normalized at 6.3 minutes.

Conclusion: This case suggests that andexanet alfa may have a role in the management of traumatic hemorrhage in the setting of an acute massive apixaban overdose. Use of andexanet alfa, PCC, and aPCC in this context requires further research
((Jenniches D, Kerns AF, DelBianco J, Stripp MP, Philp AS. Administration of andexanet alfa for traumatic intracranial hemorrhage in the setting of massive apixaban overdose: A case report. Am J Health Syst Pharm. 2023 Nov 22;80(23):1722-1728. doi: 10.1093/ajhp/zxad215. PMID: 37688311.))