Girish Hiremath, MD, FAANS
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Spontaneous ICH (sICH)
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15% of all acute strokes
Deadliest stroke subtype
 1 month mortality of 40%
 At 1 year, 75% die or are severely disabled
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Initial hematoma volume remains strongest
predictor of 30-day mortality and functional
outcome
 Only modifiable predictor of outcome
Qureshi, Lancet 2009
Van Asch, Lancet Neurol 2010
Broderick, Stroke 1993
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Larger more likely to expand
Early presentation after symptom onset
Anticoagulation use
Presence of APOE ε2 allele
CTA spot sign
Newer marker for hematoma expansion
 Poor functional outcome, death
 Low sensitivity
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Cucchiara, Stroke 2008
Broderick, Stroke 2007
Delgado, Stroke 2010
Brouwers, Stroke 2012
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Dilemma: pt with past ICH develops clear indication for A/C such as Afib
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Risk of thromboembolism is 4.5% with Afib
Efficacy of warfarin for stroke prevention: 68%
Decision analysis models (no RCT’s)
Assumptions:
Relative risk of bleeding on ASA in this cohort—SDH = 2.0
Relative risk of bleeding on A/C—ICH = 2.0; SDH = 4.0
For 1000 patients with lobar ICH, A/C would result in 31 fewer thromboembolic events,
but 150 additional ICH’s
Conclusions:
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A/C not indicated after lobar ICH
A/C resumption unclear after deep ICH (probably no unless very high risk of ischemic stroke)
ASA indicated only if RR for deep ICH is < 1.3 and for lobar ICH < 1.04
Eckman, Stroke 2003
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72 year old white man presents with expressive
aphasia, headache, declining mental status
Likely spontaneous—no specific hx of trauma
On ASA/PLAVIX for CAD
L Acute SDH (2cm) with 1cm MLS; L inferior
frontal contusion/ICH
Underwent platelet tx, emergent craniotomy,
evacuation of SDH
Redo Urgent Craniotomy…
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1 week later:
Admitted to OSH with massive MI, resulting in
resumption of ASA/PLAVIX…
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22071 male physicians (aged 40-84) randomly assigned to
325mg ASA or placebo qOD
At 5 yrs:
 ASA use was associated with 2.14 X higher risk of
hemorrhagic stroke
Swedish Aspirin Low-dose Trial (SALT)
1360 pts with hx of TIA/minor stroke randomly assigned to
75mg/d of ASA or placebo for 2.8 yrs
 ASA use associated with 2.78 X higher risk of
hemorrhagic stroke
Steering Committee of the Physicians’ Health Study Research Group; NEJM 1989
SALT Collaborative Group; Lancet 1991
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Meta-analysis of 16 RCT’s on ASA use
International study of 55462 participants
RR reduction of MI with ASA
RR reduction of ischemic stroke with ASA
RR increase in hemorrhagic stroke with ASA
(84% increased RR)
(all three were significant at P <.001)
He et al, JAMA 1998
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Meta-analysis of 1880 ICH survivors between 1982
and 2000
Mean age 65
Mean f/u: 3.4 yrs from index ICH
Stroke recurrence:
59% hemorrhagic
 26% ischemic
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Recurrent ICH occurs at 2X the rate of ischemic stroke in
survivors of primary ICH
 2.4% per year rate of recurrent ICH
 Higher risk with lobar hemorrhage
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Bailey et al; Neurology 2001
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207 patients with index ICH
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AP prescribed in 22% of survivors
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Avg of 5.4 months after index ICH
Most commonly for ischemic cardiovascular dz
ICH recurred in 22% of survivors
No increase in risk of recurrent ICH with ASA resumption
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Lobar
Deep
(p = 0.73)
ICH location not factor (lobar vs. deep)
Limitations:
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Selection bias (pts felt to be high risk for repeated ICH likely did not have
AP resumption)
Resumption of ASA did NOT significantly improve cardiovasc morbidity
(p =.75)
Small sample size (only 46 pts had recurrent ICH)
Viswanathan et al; Neurology 2006
Donnan and Ly; Neurology 2006
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Observational, Community-based study in
Scotland
417 pts with ICH
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120 prescribed Antiplatelet medications (28.8%)
Median time from d/c to AP use was 14.8 months
40 ischemic strokes/MI
14 recurrent ICH
Study found no association between AP use and
recurrent ICH
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Limitations:
 Small sample size
 Selection bias
 ? Delay in resuming of AP to 14.8 months after index ICH
Flynn et al; Stroke 2010
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There is no good answer!
No good literature to guide the neurosurgeon
(or neurologist)
There is not likely to be a RCT
In general, it is prudent to wait at least one
month
Must be made on a case-by-case basis
NOT by a “protocol-driven” approach
VTE is frequent in pts with ischemic and
hemorrhagic stroke
5% of early deaths following stroke
attributed to PE
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Incidence of DVT in untreated NS pts: 18-50%
Multiple studies have shown the safety of pharmacological DVT
prophylaxis in the setting of elective NS
In 555 pts undergoing elective NS procedures, LDSQUFH:
 Reduced DVT by 43% (measured by U/S)
 Risk reduction NOT assoc with incr hemorrhage
 Did not alter the rate of PE
 No correlation between DVT and PE
 (In general, 30% of pts with acute PE have no LE DVT)
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PE directly related only to length of procedure
(? Lack of statistical power)
Khaldi et al; J Neurosurg 2011;
Agnelli et al; NEJM 1998;
Geerts; Chest 2001
Cage et al; J Neurooncology 2009
Chibbaro Surg Neurol 2008
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133/151 evaluated at day 10 after ICH
Endpoints: a/symptomatic DVT/PE
14 asymptomatic DVT’s identified
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3 in ES only group
11 in ES + IPC group
IPC combined with graded ES reduced the risk
of asymptomatic DVT at day 10 following ICH
by 71% compared with ES alone.
Lacut et al; Neurology 2005
(VICTORIAh study)
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Meta-analysis of RCT’s of prophylactic use
(within 6 days) of SQ
UFH
 LMWH
 Heparinoids
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Endpoints:
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A/symptomatic DVT
A/symptomatic PE
Death
A/symptomatic hematoma enlargement
Paciaroni et al; J Thrombosis and Haemostasis 2011
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4 studies included
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2 used UFH
2 used LMWH
Results:
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A/C resulted in sig reduction in:
 PE
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A/C resulted in NON-sig
 Reduction in mortality
 Reduction in DVT
 Hematoma enlargement
Paciaroni et al; J Thrombosis and Haemostasis 2011
97 patients with sICH were all given LMWH in the
form of Enoxaparin or Dalteparin
2 patients developed moderate enlargement of
hematoma
No fatal PE’s
Limitations:
Non-randomized; no control group; limited sample
size
Kiphuth et al; Cerebrovasc Dis 2009
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2 cohorts of 107, 129 pts each with tICH (1 served
as a historic control)
Both groups tx with SCD’s
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Following stable Head CT, 1 group underwent tx with
either LMWH (Lovenox 30mg BID or SQUFH 5000 TID)
Group A (no tx): DVT rate was 5.6%
Group B (tx): DVT rate was 0%
No progression of ICH
NO sig difference in rate of PE (P = 0.179) with trend
towards lower rate of PE in pts undergoing
pharmacological prophylaxis
Farooqui et al; J Neurosurg 2013
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In general, rates of DVT and PE are reduced with the
use of pharmacological prophylaxis in the setting of
sICH and tICH
There is probably no significant hematoma
enlargement with the use of such prophylaxis
However, many studies show no significant correlation
between DVT and PE; some show no significant
reduction in rate of PE with pharm prophylaxis
The idea that mortality is reduced with the use of
pharmacological DVT prophylaxis is yet to be proven