Background
Acute ischemic stroke thrombolysis in patients taking dabigatran is controversial
because of a presumed increased risk of symptomatic hemorrhagic transformation. Using
data from our local hematopathology laboratory, we developed a thrombolysis protocol
for acute ischemic stroke patients taking dabigatran.
Methods
A local thrombin time (TT)–dabigatran concentration relationship was calculated using
dabigatran calibrators. The effect of dabigatran on activated partial thromboplastin
time (aPTT) and prothrombin time (PT) (international normalized ratio [INR]) was also
measured. A protocol was developed, in which a dabigatran concentration less than
10 ng/mL (corresponding to a TT < 38 seconds or a normal aPTT) was selected as the
upper limit for thrombolysis. Consecutive patients presenting with acute stroke were
then enrolled in this prospective study.
Results
In the 8 months after development of the protocol, 13 potential thrombolysis candidates
taking dabigatran were assessed at a median (interquartile range) time of 192 (143)
minutes. The median National Institutes of Health Stroke Scale score was 18 (20).
The mean time from arrival to TT, aPTT, and PT (INR) results were 39 ± 4.1 minutes,
21 ± 6.5 minutes, and 21 ± 6.5 minutes, respectively. Based on TT/aPTT, 4 patients
were ineligible for thrombolysis. Six patients were not treated because of minor or
resolving symptoms and another presented with intracerebral hemorrhage. Two patients
were treated with intravenous tissue plasminogen activator (tPA), without symptomatic
hemorrhagic transformation in either case. In 3 patients (42.8%), aPTT was normal,
despite a prolonged TT.
Conclusions
Administration of intravenous tPA in dabigatran-treated patients is feasible. Although,
the relationship between dabigatran concentrations and coagulation measures varies
between laboratories, individual protocols, preferably based on TT, can be developed
at acute stroke treatment centers.
Key Words
To read this article in full you will need to make a payment
Purchase one-time access:
Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online accessOne-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:
Subscribe to Journal of Stroke and Cerebrovascular DiseasesAlready a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
References
- National trends in oral anticoagulant use in the United States, 2007 to 2011.Circ Cardiovasc Qual Outcomes. 2012; 5: 615-621
- Subtherapeutic warfarin therapy entails an increased bleeding risk after stroke thrombolysis.Neurology. 2012; 79: 31-38
- Risks of intracranial hemorrhage among patients with acute ischemic stroke receiving warfarin and treated with intravenous tissue plasminogen activator.JAMA. 2012; 307: 2600-2608
- Dabigatran etexilate—a novel, reversible, oral direct thrombin inhibitor: interpretation of coagulation assays and reversal of anticoagulant activity.Thromb Haemost. 2010; 103: 1116-1127
- Hyperfibrinogenemia as a cause of prolonged thrombin clotting time.Southern Med J. 1986; 79: 563-570
- Classification and pathogenesis of cerebral hemorrhages after thrombolysis in ischemic stroke.Stroke. 2006; 37: 556-561
- A comparison of dabigatran etexilate with warfarin in patients with mechanical heart valves: the randomized, phase II study to evaluate the safety and pharmacokinetics of oral dabigatran etexilate in patients after heart valve replacement (RE-ALIGN).Am Heart J. 2012; 163: 931-937.e1
- Preadmission antithrombotic treatment and stroke severity in patients with atrial fibrillation and acute ischaemic stroke: an observational study.Lancet Neurol. 2006; 5: 749-754
- Acute ischemic stroke treated with intravenous tissue plasminogen activator in a patient taking dabigatran with radiographic evidence of recanalization.J Stroke Cerebrovas Dis. 2012; 21: 917.e5-917.e9
- Thrombolysis treatment for acute ischaemic stroke in a patient on treatment with dabigatran.Thromb Haemost. 2011; 106: 178-179
- Intravenous thrombolysis with recombinant tissue plasminogen activator in a stroke patient treated with dabigatran.Cerebrovasc Dis. 2010; 30: 533-534
- Thrombolysis in an ischemic stroke patient on dabigatran anticoagulation: a case report.Cerebrovasc Dis. 2012; 34: 246-247
- Intravenous thrombolysis in a stroke patient taking dabigatran.J Stroke Cerebrovas Dis. 2012; 21: 916.e11-916.e12
- Fatal intracerebral hemorrhage associated with administration of recombinant tissue plasminogen activator in a stroke patient on treatment with dabigatran.Cerebrovasc Dis. 2011; 32: 614-615
- Dabigatran versus warfarin in patients with atrial fibrillation.N Engl J Med. 2009; 361: 1139-1151
- Treatment of acute stroke in patients on dabigatran: A survey of us stroke specialists.J Stroke Cerebrovas Dis. 2013; 22: 1312-1316
Article info
Publication history
Published online: January 09, 2014
Accepted:
November 13,
2013
Received in revised form:
November 7,
2013
Received:
July 23,
2013
Footnotes
Disclosure: None.
Identification
DOI: https://doi.org/10.1016/j.jstrokecerebrovasdis.2013.11.013
Copyright
© 2014 National Stroke Association. Published by Elsevier Inc. All rights reserved.