title: Standardized use of novel oral anticoagulants plasma level thresholds in a new thrombolysis decision making protocol.
abstract: Acute ischemic stroke (AIS) patients receiving non-vitamin-K antagonist oral anticoagulants (NOAC) are commonly excluded from thrombolytic therapy, as interpretation of coagulation tests remains unclear. We aimed to investigate the applicability of a novel institutional protocol for thrombolysis based on current expert recommendations and NOAC specific coagulation assessment. We included hospitalized AIS patients receiving NOAC for at least 24 h and consecutive AIS patients not receiving NOAC into a prospective study. We performed standard coagulation tests and specific tests for dabigatran, rivaroxaban and apixaban plasma levels. We studied 65 patients: mean age 72 ± 13 years, 30 (46 %) male, median NIHSS score 3 (IQR 6). Fifteen (23 %) were on NOAC treatment (5 dabigatran, 5 rivaroxaban, and 5 apixaban, respectively) and 50 (77 %) were not. In patients without NOAC, dabigatran was not detectable (0 ng/ml), and plasma levels of rivaroxaban (median: 10.0 ng/ml, IQR 7.0) and apixaban (7.2 ng/ml, IQR 6.7) were below our lower thresholds that allow thrombolysis. In patients with dabigatran pre-treatment, trough levels (58.0 ng/ml, IQR 143.0) were below our upper threshold that would allow thrombolysis in 3/5 patients. In patients receiving rivaroxaban, trough level (68.0 ng/ml, IQR 64.0) was below our predefined upper thresholds that would allow thrombolysis in 4/5 patients. In all patients on apixaban, trough level was above our predefined threshold of 40 ng/ml that precludes thrombolysis (98.2 ng/ml, IQR 84.3). Predefined thresholds of NOAC plasma levels in the decision of thrombolysis in NOAC treated AIS patients might supplement routine coagulation tests and should be validated in a larger study population.
authors.affiliation: Department of Neurology, Carl Gustav Carus University Hospital, Technische Universität Dresden, Fetscherstrasse 74, 01307, Dresden, Germany. Jessica.kepplinger@uniklinikum-dresden.de.
authors.forename: Jessica
authors.initials: J
authors.lastname: Kepplinger
authors.affiliation: Department of Neurology, Carl Gustav Carus University Hospital, Technische Universität Dresden, Fetscherstrasse 74, 01307, Dresden, Germany.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Prakapenia
authors.affiliation: Department of Neurology, Carl Gustav Carus University Hospital, Technische Universität Dresden, Fetscherstrasse 74, 01307, Dresden, Germany.
authors.forename: Kristian
authors.initials: K
authors.lastname: Barlinn
authors.affiliation: Institute of Clinical Chemistry and Laboratory Medicine, Carl Gustav Carus University Hospital, Technische Universität Dresden, Dresden, Germany.
authors.forename: Gabriele
authors.initials: G
authors.lastname: Siegert
authors.affiliation: Institute of Clinical Chemistry and Laboratory Medicine, Carl Gustav Carus University Hospital, Technische Universität Dresden, Dresden, Germany.
authors.forename: Siegmund
authors.initials: S
authors.lastname: Gehrisch
authors.affiliation: Department of Neurology, Carl Gustav Carus University Hospital, Technische Universität Dresden, Fetscherstrasse 74, 01307, Dresden, Germany.
authors.forename: Charlotte
authors.initials: C
authors.lastname: Zerna
authors.affiliation: Department of Internal Medicine, Carl Gustav Carus University Hospital, Technische Universität Dresden, Dresden, Germany.
authors.forename: Jan
authors.initials: J
authors.lastname: Beyer-Westendorf
authors.affiliation: Department of Neurology, Carl Gustav Carus University Hospital, Technische Universität Dresden, Fetscherstrasse 74, 01307, Dresden, Germany.
authors.forename: Volker
authors.initials: V
authors.lastname: Puetz
authors.affiliation: Department of Neurology, Carl Gustav Carus University Hospital, Technische Universität Dresden, Fetscherstrasse 74, 01307, Dresden, Germany.
authors.forename: Heinz
authors.initials: H
authors.lastname: Reichmann
authors.affiliation: Department of Neurology, Carl Gustav Carus University Hospital, Technische Universität Dresden, Fetscherstrasse 74, 01307, Dresden, Germany.
authors.forename: Timo
authors.initials: T
authors.lastname: Siepmann
authors.affiliation: Department of Neurology, Carl Gustav Carus University Hospital, Technische Universität Dresden, Fetscherstrasse 74, 01307, Dresden, Germany.
authors.forename: Ulf
authors.initials: U
authors.lastname: Bodechtel
mesh_terms: D000284:Administration, Oral; D000368:Aged; D000369:Aged, 80 and over; D000925:Anticoagulants / Q000008:administration & dosage / Q000493:pharmacokinetics; D002545:Brain Ischemia / Q000097:blood / Q000188:drug therapy; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D020521:Stroke / Q000097:blood / Q000188:drug therapy; D015912:Thrombolytic Therapy / Q000379:methods*
chemical_list: D000925:Anticoagulants
keywords: Acute ischemic stroke; Novel oral anticoagulants; Thrombolysis