Letter by Kallmünzer et al Regarding Article, “Safety of Intravenous Thrombolysis Among Patients Taking Direct Oral Anticoagulants: a Systematic Review and Meta-Analysis”

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HomeStrokeVol. 51, No. 7Letter by Kallmünzer et al Regarding Article, “Safety of Intravenous Thrombolysis Among Patients Taking Direct Oral Anticoagulants: a Systematic Review and Meta-Analysis” Free AccessLetterPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyRedditDiggEmail Jump toFree AccessLetterPDF/EPUBLetter by Kallmünzer et al Regarding Article, “Safety of Intravenous Thrombolysis Among Patients Taking Direct Oral Anticoagulants: a Systematic Review and Meta-Analysis” Bernd Kallmünzer, MD, Michael Pott, MD and Stefan Schwab, MD Bernd KallmünzerBernd Kallmünzer https://orcid.org/0000-0003-3552-6742 Department of Neurology, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nuremberg, Germany (B.K., S.S.). Department of Neurology, Klinikum Bayreuth GmbH, Bayreuth, Germany. Search for more papers by this author , Michael PottMichael Pott Search for more papers by this author and Stefan SchwabStefan Schwab Department of Neurology, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nuremberg, Germany (B.K., S.S.). Department of Neurology, Klinikum Bayreuth GmbH, Bayreuth, Germany. Search for more papers by this author Originally published16 Jun 2020https://doi.org/10.1161/STROKEAHA.120.029631Stroke. 2020;51:e130–e131To the Editor:With great interest we read the article “Safety of Intravenous Thrombolysis Among Patients Taking Direct Oral Anticoagulants” by Shahjouei et al.1 Before the use of rtPA in patients on oral anticoagulation, it seems reasonable to use antidots for anticoagulation reversal. Andexanet alfa, a recombinant form of the human factor Xa, rapidly reduces the anticoagulatory effect of factor Xa inhibitors2 and was recently approved for emergent reversal of oral anticoagulation in patients on treatment with apixaban or rivaroxaban.Recently, a 77-year-old woman presented to a German hospital with an acute ischemic stroke causing serious left-sided hemiparesis and dysarthria 2 hours after symptom onset. Computed tomography angiography confirmed an occlusion of the right medial cerebral artery at the proximal segment. The condition demanded an immediate treatment with alteplase followed by the transfer to a neurovascular center for mechanical thrombectomy. The patient suffered from permanent atrial fibrillation and used apixab (5 mg b.i.d.) for the prevention of thromboembolism. She had taken the last dose of apixaban 3 hours before admission. A chromogenic assay found the calibrated antifactor Xa activity being elevated to 188 ng/mL, which formally contradicted the use of recombinant tissue plasminogen activitor (r-tPA). Therefore, it was decided to reverse the effect of apixaban before intravenous thrombolysis: The patient received an intravenous bolus of 400 mg andexanet alfa at a target rate of 30 mg/minute. A continuous infusion of 480 mg followed for 2 hours, resulting in a total dose of 880 mg andexanet alfa. Treatment with alteplase was initiated as soon as the andexanet alfa bolus had been administered. r-tPA total dose was 90 mg (9 mg bolus followed by a 1-hour infusion of 81 mg) and the patient started immediate transfer to the thrombectomy center. On arrival, her neurological symptoms had markedly improved. The MCA occlusion showed complete recanalization before endovascular treatment. Ten hours after symptom onset, the anti-factor Xa activity had spontaneously increased to 277 ng/mL and remained elevated during the first days. No hemorrhagic complications occurred. The estimated glomerular filtration rate was 58 mL/minute.The use of alteplase in patients on treatment with direct oral anticoagulants has not been firmly established.1 For dabigatran, it seems feasible to reverse the anticoagulant by idarucizumab before the initiation of intravenous thrombolysis.3 Unlike idarucizumab, the characteristics of andexanet alfa result in an incomplete and only transient reduction of the antithrombotic activity.2,4 Consistently, a rebound even beyond the level on admission occurred in this patient at 10 hours after symptom onset. As the frequency of hemorrhagic complications raises with higher anticoagulant peak levels,5 this secondary increase will caution the clinician about an elevated risk of r-tPA associated bleeding, despite the use of Andexanet alfa.AcknowledgmentsWe thank Professor Erwin Strasser, Department for Hemostaseology and Transfusion Medicine, University Hospital Erlangen, for the measurements of the anti-Factor Xa Activitity.DisclosuresDr Kallmünzer reports speaker honoraria from BMS Pfizer, Daiichi Sankyo, Bayer AG and Medtronic, outside the submitted work. Dr Schwab reports speaker honoria and travel grants from Boehringer Ingelheim, Pfizer, Daiichi Sankyo. The other authors report no conflicts.FootnotesFor Disclosures, see page e130.