Case

Report

Intravenous Thrombolysis for Acute Ischemic Stroke in a PatientReceiving Rivaroxaban

Anne Landais, MD,* and Caroline Ginoux, MD†

From the *Neurology

�a-Pitre, Route de Chauv

Unit, University Hospi

Abymes Guadeloupe, Fr

Received July 2, 2014;

A.L. has received com

Healthcare and Boehring

Address corresponden

ment, University Hospita

Abymes Guadeloupe, Fr

1052-3057/$ - see front

� 2015 by National Str

http://dx.doi.org/10.1

Journal of Stroke and C

Background: Rivaroxaban is an oral direct factor Xa inhibitor increasingly used in

stroke prevention in nonvascular atrial fibrillation, primary prevention and treat-

ment of venous thromboembolism, and secondary prevention in acute coronary

syndromes. Methods: Thrombolytic treatment has established efficacy in acute

ischemic stroke. Results: We report the case of a 76-year-old female under rivaroxa-

ban for paroxysmal nonvalvular atrial fibrillation who presented an acute ischemic

stroke. The brain magnetic resonance imaging diffusion-weighted sequences

showed increased signal in the territory of the left middle cerebral artery. Platelet

count was normal. PTwas 55% (normal, 70-120); the international normalized ratio

was 1.51 (normal, .90-1.40). She underwent intravenous thrombolysis 210 minutes

after stroke onset without bleeding complication and with complete clinical recov-

ery. Conclusions: This case underlines the need for further studies on the safety of

thrombolysis in stroke patients taking rivaroxaban. Our case emphasizes the urgent

need for sensitive coagulation bed-side tests during stroke emergencies. Key Words:

Acute stroke—thrombolysis—rivaroxaban—new direct oral anticoagulant.

� 2015 by National Stroke Association

Rivaroxaban is an oral direct factor Xa inhibitor increas-

ingly used in stroke prevention in nonvascular atrial

fibrillation, primary prevention and treatment of venous

thromboembolism, and secondary prevention in acute

coronary syndromes. Thrombolytic treatment (rt-PA)

has established efficacy in acute ischemic stroke.1

We report the case of a 76-year-old female with past

medical history of paroxysmal nonvalvular atrial fibrilla-

Department, University Hospital of Pointe-

el, Abymes Guadeloupe; and †Emergency

tal of Pointe-�a-Pitre, Route de Chauvel,

ance.

accepted October 27, 2014.

pensation for travel expenses from Bayer

er Ingelheim. C.G. has nothing to disclose.

ce to Anne Landais, MD, Neurology Depart-

l of Pointe-�a-Pitre, Route de Chauvel, 97139

ance. E-mail: landais-anne@voila.fr.

matter

oke Association

016/j.jstrokecerebrovasdis.2014.10.014

erebrovascular Diseases, Vol. -, No. - (---

tion, heart failure (New York Heart Association class I),

pulmonary embolism, and hypertension, who presented

to the emergency department for brutal-onset aphasia at

8.15 am.

Five days previously, she had come to the emergency

department for cardiac decompensation; a paroxysmal

atrial fibrillation was diagnosed and treatment by rivar-

oxaban 15 mg once daily (although the creatinine clear-

ance according to the Cockroft–Gault formula was

57 mL/minute, thus needing no dosage adjustment)

was introduced by the cardiologist before she returned

home where she took her treatment regularly. The last

intake was at 6.00 am.

On arrival, she presented with isolated aphasia

without any motor deficit, the National Institute of

Health Stroke Score score on admission was 4. The brain

magnetic resonance imaging diffusion-weighted se-

quences showed increased signal in the territory of the

left middle cerebral artery (Fig 1) with left M2 branches

less visible than right ones on time of flight sequence.

Blood pressure was 132/85 mm Hg. Platelet count was

), 2015: pp e1-e2 e1

Figure 1. Brain magnetic resonance imaging Diffusion-weighted sequence

showing increased signal in the territory of the left middle cerebral artery.

A. LANDAIS AND C. GINOUXe2

normal (265,000 [150,000-400,000]). Prothrombin time

was 55% (normal, 70-120); the international normalized

ratio (INR) was 1.51 (normal, .90-1.40), fibrinogen was

5.44 g/L (1.7-4). No other coagulation test was available

in emergency in our hospital. Particularly, we did not

have specific rivaroxaban plasma concentration dosage

and specific anti–factor Xa activity.

After discussion with the family concerning the risk of

major and eventually fatal bleeding during thrombolysis

under NOAC, and after they decided to take the risk and

gave their consent, the patient received 63 mg rt-PA

3 hours and 30 minutes (210 minutes) after onset of symp-

toms and 5 hours and 45 minutes (345 minutes) after the

last intake of rivaroxaban. She rapidly improved to an

NIHSS of 0 and completely recovered from her aphasia.

The control computed tomography scan performed the

day after showed no hemorrhagic transformation.

Discussion

There are few reports about strokes under rivaroxaban,

their treatment, and outcome.2,3 It is possible that the

favorable clinical outcome and the absence of bleeding

complications in our case are related to the reduced

dose of rivaroxaban. Assays measuring specific

anticoagulation effects are not always available but

should be performed before rt-PA is given, as PT/INR in

patients under vitamin K antagonist.4 Our case empha-

sizes the need for sensitive bed-site tests during emergen-

cies. Recent guidelines recommend that intravenous

thrombolysis in rivaroxaban-treated patients may be

considered if the plasma concentration of rivaroxaban is

less than 100ng/L5 or if anti–factor Xa activity is normal.1,5

Further studies on thrombolysis in patients taking

rivaroxaban are necessary, attempting to establish precise

thresholds of anti–factor Xa activity under which it

would be safe, as with patients anticoagulated by

vitamin K antagonist, its use is contraindicated for those

with an INR of 1.7 or more. Antagonists for new oral

anticoagulant drugs are under development, and it is

possible that these antagonists may not induce a

procoagulant response. Thrombolysis would therefore be

possible.

References

1. Jaunch EC, Saver JL, Adams HP, et al. Guidelines for theearly management of patients with acute ischemic stroke:a guideline for health professionals from the AmericanHeart Association/American Stroke Association. Stroke2013;44:870-947.

2. Fluri F, Heinen F, Kleinschnitz C. Intravenous thromboly-sis in a stroke patient receiving rivaroxaban. CerebrovasDis Extra 2013;3:153-155.

3. Van Hooff R-J, Nieboer K, De Smedt A, et al. Intravenousthrombolysis with recombinant tissue plasminogen acti-vator for acute ischemic stroke in a patient treated with ri-varoxaban. Clin Neurol Neurosurg 2014;122:131-132.

4. Samama MM, Constant G, Spiro TE, et al. Laboratoryassessment of rivaroxaban: a review. Thromb J 2013;11:11.

5. Steiner T, B€ohm M, Dichgans M, et al. Recommendationsfor the emergency management of complications associ-ated with the new direct oral anticoagulants (DOACs),apixaban, dabigatran and rivaroxaban. Clin Res Cardiol2013;102:399-412.