Update: Rivaroxaban in neurosurgery

Rivaroxaban

J.Sales-Llopis

Neurosurgery Department, University General Hospital of Alicante, Foundation for the Promotion of Health and Biomedical Research in the Valencian Region (FISABIO), Alicante, Spain

Rivaroxaban (BAY 59-7939) is an oral anticoagulant invented and manufactured by Bayer; in a number of countries it is marketed as Xarelto. In the United States, it is marketed by Janssen Pharmaceutica.

It is the first available orally active direct factor Xa inhibitor. Rivaroxaban is well absorbed from the gut and maximum inhibition of factor Xa occurs four hours after a dose. The effects last approximately 8–12 hours, but factor Xa activity does not return to normal within 24 hours so once-daily dosing is possible 1).

Thrombolysis and/or endovascular thrombectomy might be safe for patients treated with the new anticoagulant rivaroxaban 2).

Complications

Despite several advantages of the novel anticoagulant rivaroxaban compared with vitamin K antagonists (VKA), its lack of specific antidotes to reverse anticoagulant effects may increase the risk profile of patients with bleeding complications.

There are few studies in the literature regarding the presence of intracerebral hemorrhage and the volume and prognosis of bleeding associated with rivaroxaban 3).

The results suggest that rivaroxaban may exacerbate intracranial haemorrhage in patients with mild traumatic brain injury (TBI) 4).

Case series

A total of 70 patients with traumatic intracranial hemorrhage (tICH) after mild traumatic brain injury (TBI) were included in a retrospective analysis and were categorized into three groups: group A (no antithrombotics n=37), group B (antiplatelet medication n=22, VKA=5), and group C (rivaroxaban n=6). Medical charts were reviewed for baseline characteristics, laboratory values, intracranial haemorrhage, repeated computed tomography (CT) scans, re-haemorrhage, Glasgow Coma Scale (GCS) scores and in-hospital mortality.

No significant differences were observed for baseline characteristics. The rate of re-haemorrhage was significantly higher in group C (50%) than in group A (11%) (p<0.05). Two patients died and both had been treated with rivaroxaban which resulted in a significantly higher mortality rate of 33% in group C compared with groups A (0%) and B (0%). No significant differences were observed for GCS at discharge and length of hospital stay between survivors of groups A-C.

Despite major limitations of retrospective design and small patient numbers, the results suggest that rivaroxaban may exacerbate intracranial hemorrhage in patients with mild TBI. Further studies are needed to characterize the risk profile of this drug in patients with tICH 5).

Case reports

2015

The clinical and radiologic findings and follow-up of an 80-year-old male patient with intracerebral hemorrhage who uses rivaroxaban for anticoagulation are presented in the article of Çalışkan et al. 6).

2014

Ishihara et al. report an acute stroke patient taking rivaroxaban who received intravenous thrombolysis with recombinant tissue plasminogen activator (rt-PA). An 80-year-old man with a history of nonvalvular atrial fibrillation, who had been receiving 10 mg of rivaroxaban showed abrupt onset of aphasia and right hemiparesis. National Institutes of Health Stroke Scale score was 10. Onset of neurologic deficits occurred 4 hours after the last dose of rivaroxaban. Clinical data on admission were as follows: blood pressure, 170/90 mm Hg; prothrombin time (PT), 22.6 seconds (control, 12.9 seconds); international normalized ratio, 2.03; activated partial thromboplastin time, 46 seconds (normal, 23-32 seconds); and creatinine level, 1.11 mg/dL. Magnetic resonance angiography revealed occlusion of the superior trunk of the left middle cerebral artery. Intravenous infusion of .6 mg/kg of rt-PA (total dose, 36 mg) was performed 6 hours after the last rivaroxaban administration with informed consent. The neurologic deficit improved during infusion of rt-PA. Repeat brain computed tomography showed left frontal cortical infarction without hemorrhagic changes. In the case of rivaroxaban, it is difficult to accurately determine the drug activity. As the anticoagulant activity of rivaroxaban can be estimated from its pharmacokinetics and PT, it is clinically important to obtain accurate information about the timing of medication and blood sampling 7).


A 83-year-old woman had a medical history with ischemic stroke due to paroxysmal atrial fibrillation and was then administered 10 mg of rivaroxaban daily. Although she took rivaroxaban in the morning, ischemic stroke recurred at midnight of that day. Soon after transferring to the hospital, Kimura et al. confirmed right middle cerebral artery (MCA) occlusion in the patient and then initiated treatment with intravenous rt-PA. Although no hemorrhagic complication occurred, recovery of her symptoms was not seen, and endovascular thrombectomy was performed. Although the inferior branch of the MCA was recanalized, an infarct was seen in her left frontal lobe. Hemorrhagic transformation was not observed during or after these combined treatments 8).

1) Komotar RJ, Starke RM, Connolly ES Jr. Orally administered factor xa inhibitor, rivaroxaban: a novel thromboembolic prophylaxis agent. Neurosurgery. 2008 Oct;63(4):N10-1. doi: 10.1227/01.NEU.0000339454.55968.F0. PubMed PMID: 18981864.
2) , 8) Kimura S, Ogata T, Fukae J, Okawa M, Higashi T, Iwaasa M, Inoue T, Tsuboi Y. Revascularization for acute ischemic stroke is safe for rivaroxaban users. J Stroke Cerebrovasc Dis. 2014 Oct;23(9):e427-31. doi: 10.1016/j.jstrokecerebrovasdis.2014.05.015. Epub 2014 Aug 20. PubMed PMID:25149204.
3) , 6) Çalışkan F, Akdemir HU, Nurata H, Akdemir N, Başara G, Yavuz Y.Rıvaroxaban-induced severe diffuse ıntracerebral hemorrhage. Am J Emerg Med. 2015 Mar;33(3):475.e1-5. doi: 10.1016/j.ajem.2014.08.028. Epub 2014 Aug 21. PubMed PMID: 25218622.
4) , 5) Beynon C, Potzy A, Sakowitz OW, Unterberg AW. Rivaroxaban and intracranial haemorrhage after mild traumatic brain injury: A dangerous combination? Clin Neurol Neurosurg. 2015 May 30;136:73-78. doi: 10.1016/j.clineuro.2015.05.035. [Epub ahead of print] PubMed PMID: 26070116.
7) Ishihara H, Torii H, Imoto H, Oka F, Sadahiro H, Suzuki M. Intravenous thrombolysis with recombinant tissue plasminogen activator in a stroke patient treated with rivaroxaban. J Stroke Cerebrovasc Dis. 2014 Nov-Dec;23(10):e457-9. doi: 10.1016/j.jstrokecerebrovasdis.2014.07.008. Epub 2014 Oct 3. PubMed PMID: 25280819.

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