Jurnal 15

The Dilemma of Resuming Anticoagulation After
Intracranial Hemorrhage
Little Evidence Facing Big Fears
Carlos A. Molina, MD, PhD; Magdy H. Selim, MD, PhD
ntracranial hemorrhage (ICH) is the most feared and

devastating complication of anticoagulant treatment, leading to death or disability in two thirds of cases. Once ICH
occurs, the decision of whether to resume anticoagulation is a
true therapeutic dilemma that requires balancing the competing risks of hematoma growth or recurrent ICH and disabling
thromboembolic events.
Although the risk of thromboembolism in patients off
anticoagulation is higher than the overall risk of ICH recurrence, there is a marked paucity of prospective large
population-based data on the real risk of ICH recurrence on
warfarin. The lack of randomized controlled trials probably
reflects the ethical challenge of prescribing patients a medication to which they have an apparent contraindication.
Therefore, in clinical practice, the risk is usually, and inappropriately, extrapolated from the overall risk of major
bleeding on warfarin (approximately 3%), in which older age
and elevated international normalized ratio are factors associated with an increased risk.
The little evidence available on resuming oral anticoagulation after ICH comes from either expert opinions or few
nonrandomized mainly retrospective studies.1,2 These studies
included highly selected high-risk patients and showed nonconclusive and even discrepant results. This limited and weak
evidence along with our own experience and common sense
are the weapons that our protagonists use for facing the
physicians fears and uncertainties of increasing the risk of a
devastating recurrent ICH or leaving the patient unprotected
from thromboembolic complications. Dr Shulmans argument
is based on the high risk of recurrent ICH on warfarin after
ICH at any location and gives a broad recommendation of
abstaining from resuming warfarin. He argues that in our
case, warfarin should not be resumed because the risk of
recurrent ICH (15%) is more than twice as high as the risk of
ischemic stroke (6%). Dr Steiner delineates a more restrictive
scenario, in which the risk of thromboembolism outweighs
the risk of ICH recurrence in a hypertensive-related, nonlobar
ICH. He recommends that warfarin should be restarted if
blood pressure and other risk factors are adequately

controlled.
Among all factors associated with an increased risk of
recurrent ICH on warfarin, ICH location and documented
history of thromboembolism seem to be the key factors that
tilt the risk/benefit balance of restarting anticoagulation after
ICH. In 1 of the only 2 published epidemiological studies, the
risk of recurrent ICH on warfarin was 5-fold higher in lobar
compared with deep ICH, although the rate of survival among
patients with deep ICH was low. The topographical location
of ICH may reflect the underlying microvascular pathology.
Lobar ICH in the aged population is associated with cerebral
amyloid angiopathy and an inherent high risk of recurrence.
Deep ICH is often hypertension-related. Although improved
management of hypertension can reduce the risk of recurrent
deep ICH, there is limited room for improving management
in lobar ICH if blood pressure is well controlled. On the other
hand, in an analysis of 52 patients, thromboembolic events
occurred in 48% of patients in whom warfarin was not
restarted, all of them were being treated for a previous event,
suggesting that secondary rather than primary prevention is a
stronger indication for resuming anticoagulation.2
The dilemma of restarting oral anticoagulation in the
long-term management of ICH may be better addressed by
considering other factors, including the underlying reason for
which the patient was originally started on anticoagulation,
difficulties in controlling the international normalized ratio,
the risk of thromboembolic stroke based on the CHADS2
score, and the presence and extent of microbleeds on
gradient-echo MRI. Deep ICH, secondary prevention, high
CHADS2 score, mechanical valve, or hypercoagulable state
are factors arguing in favor of resumption of anticoagulation.
Conversely, lobar ICH, presence of multiple microbleeds on
MRI, low CHADS2 score, and difficulties controlling international normalized ratio configure an unfavorable risk/
benefit profile. In addition to these factors, the decision of
whether to resume anticoagulation must take into consideration the underlying cause of ICH. For example, treatable
The opinions expressed in this article are not necessarily those of the editors or of the American Heart Association. This article is Part 3 of a 3-part
article. Parts 1 and 2 appear on pages 3661 and 3663, respectively.
Received August 1, 2011; accepted August 8, 2011.
From Hospital ValldHebron-Barcelona (C.A.M.), Barcelona, Spain; and the Stroke Division (M.H.S.), Beth Israel Deaconess Medical Center, Boston, MA.
Correspondence to Carlos A. Molina, MD, PhD, Stroke Unit, Department of Neurosciences, Hospital ValldHebron-Barcelona, Passeig Vall dHebron
119-129, 08035, Barcelona, Spain. E-mail cmolina@vhebron.net; and Magdy H. Selim, MD, PhD, Beth Israel Deaconess Medical Center, Stroke
Division, 330 Brookline Avenue, Palmer 127, Boston, MA 02215. E-mail mselim@bidmc.harvard.edu
(Stroke. 2011;42:3665-3666.)
2011 American Heart Association, Inc.
Stroke is available at http://stroke.ahajournals.org
DOI: 10.1161/STROKEAHA.111.631689
Downloaded from http://stroke.ahajournals.org/

by guest on June 21, 2015
3665
3666
Stroke
December 2011
secondary causes of ICH such as an arteriovenous malformation, in which concomitant use of anticoagulation is only
guilty by association, may not pose a risk for ICH recurrence
once treated; and traumatic ICH in the setting of anticoagulant use does not necessarily imply increased risk for ICH
recurrence.
The optimal timing for resumption of anticoagulation after
ICH is unresolved. In the acute phase, the risk of continuous
bleeding from restarting anticoagulation exceeds the risk of
thromboembolism from withholding it. Later on, the risk of
stroke and systemic embolism in the absence of anticoagulation outweighs that of rebleeding. Therefore, both the American Heart Association and the European Stroke Initiative
recommend that in patients with high risk of thromboembolism, anticoagulation should be restarted between 7 and 10
days. Dr Shulman and his colleagues, however, questioned
these recommendations and suggested that the optimal time
for resumption of anticoagulation is after 10 weeks. Clearly,
the timing depends on the indication for anticoagulation and
the patients comorbidities.
In patients with atrial fibrillation and an unfavorable
risk/benefit profile to restarting anticoagulation, antiplatelet
therapy is a reasonable alternative. In some, the use of a left
atrial appendage occlusion device or procedure may be
another consideration. Although dabigatran has demonstrated
fewer bleeding complications in patients with atrial fibrillation, compared with warfarin, safety and efficacy data in
patients with ICH is lacking.
The current dilemma is likely to persist despite ongoing
efforts to develop decision-support tools given the heterogeneity of the underlying causes of anticoagulation-related ICH
and patient populations. It exemplifies the fact that medicine
is an art and that the decision of whether and when to resume
anticoagulation after ICH should be made on an individual
case-by-case basis after taking into considerations the patients risk factors for thromboembolism and his or her
preferences after a thorough discussion of the risks versus
benefits.
Disclosures
None.
References
1. De Vleeschouwer S, Van Calenbergh F, van Loon J, Nuttin B, Goffin J,
Plets C. Risk analysis of thromboembolic and recurrent bleeding events in
the management of intracranial hemorrhage due to oral anticoagulation.
Arch Chir Belg. 2005;105:268 274.
2. Classen DO, Kazemi N, Zubkov AY, Wijdicks EF, Rabinstein AA.
Restarting anticoagulation therapy after warfarin-associated intracranial
hemorrhage. Arch Neurol. 2008;65:13131318.
KEY WORDS: acute stroke
hemorrah
Downloaded from http://stroke.ahajournals.org/ by guest on June 21, 2015
intracranial stenosis
4(24)2011

- :

. C.A. Molina, M.H. Selim. The dilemma of resuming anticoagulation after intracranial hemorrhage.
Little evidence facing big fears. Stroke 2011;42:12:36653666.
Hospital ValldHebron-Barcelona, Barcelona, Spain; and the Stroke Division, Beth Israel Deaconess Medical Center, Boston, MA.
: (acute stroke), (hemorrah), (intracranial stenosis)
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: Carlos A. Molina, MD, PhD, Stroke Unit,
Department of Neurosciences, Hospital ValldHebron-Barcelona, Passeig
Vall dHebron 119-129, 08035, Barcelona, Spain. E-mail: cmolina@vhebron.
net. Magdy H. Selim, MD, PhD, Beth Israel Deaconess Medical Center, Stroke
Division, 330 Brookline Avenue, Palmer 127, Boston, MA 02215.
E-mail: mselim@bidmc.harvard.edu
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1. De Vleeschouwer S., Van Calenbergh F., van Loon J., Nuttin B.,
Goffin J., Plets C. Risk analysis of thromboembolic and recurrent
bleeding events in the management of intracranial hemorrhage due
to oral anticoagulation. Arch Chir Belg. 2005;105:268274.
2. Classen D.O., Kazemi N., Zubkov A.Y., Wijdicks E.F., Rabinstein A.A.
Restarting anticoagulation therapy after warfarin-associated
74
intracranial hemorrhage. Arch Neurol. 2008;65:13131318.

3. Schulman S. Resumption of oral anticoagulation after warfarinassociated intracerebral hemorrhage: no. Stroke 2011;42:12:3663
3664.
4. Steiner T. Resumption of oral anticoagulation after warfarin-associated
intracerebral hemorrhage: yes. Stroke 2011;42:12:36613662.
The Dilemma of Resuming Anticoagulation After Intracranial Hemorrhage: Little

Evidence Facing Big Fears
Carlos A. Molina and Magdy H. Selim
Stroke. 2011;42:3665-3666; originally published online November 3, 2011;
doi: 10.1161/STROKEAHA.111.631689
Stroke is published by the American Heart Association, 7272 Greenville Avenue, Dallas, TX 75231
Copyright 2011 American Heart Association, Inc. All rights reserved.
Print ISSN: 0039-2499. Online ISSN: 1524-4628
The online version of this article, along with updated information and services, is located on the
World Wide Web at:
http://stroke.ahajournals.org/content/42/12/3665
Data Supplement (unedited) at:

http://stroke.ahajournals.org/content/suppl/2013/10/08/STROKEAHA.111.631689.DC1.html
Permissions: Requests for permissions to reproduce figures, tables, or portions of articles originally published
in Stroke can be obtained via RightsLink, a service of the Copyright Clearance Center, not the Editorial Office.
Once the online version of the published article for which permission is being requested is located, click
Request Permissions in the middle column of the Web page under Services. Further information about this
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The Dilemma of Resuming Anticoagulation After

ntracranial hemorrhage (ICH) is the most feared and

blood pressure and other risk factors are adequately

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intracranial hemorrhage. Arch Neurol. 2008;65:13131318.

The Dilemma of Resuming Anticoagulation After Intracranial Hemorrhage: Little

Data Supplement (unedited) at:

Downloaded from http://stroke.ahajournals.org/ by guest on June 21, 2015

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