Antithrombotic management in the setting of Intracerebral Hemorrhage

Antithrombotics and Intracerebral Hemorrhage: When is is safe to restart?

Antithrombotic management in the setting of Intracerebral HemorrhageGirish Hiremath, MD, FAANS

IntroductionSpontaneous ICH (sICH)15% of all acute strokesDeadliest stroke subtype 1 month mortality of 40%At 1 year, 75% die or are severely disabled

Initial hematoma volume remains strongest predictor of 30-day mortality and functional outcomeOnly modifiable predictor of outcomeQureshi, Lancet 2009Van Asch, Lancet Neurol 2010Broderick, Stroke 1993

Hematoma VolumeLarger more likely to expandEarly presentation after symptom onsetAnticoagulation usePresence of APOE 2 alleleCTA spot signNewer marker for hematoma expansionPoor functional outcome, deathLow sensitivityCucchiara, Stroke 2008Broderick, Stroke 2007Delgado, Stroke 2010Brouwers, Stroke 2012Should patients be anticoagulated after a history of ICH?Dilemma: pt with past ICH develops clear indication for A/C such as AfibRisk of thromboembolism is 4.5% with AfibEfficacy of warfarin for stroke prevention: 68%

Decision analysis models (no RCTs)

Assumptions:Relative risk of bleeding on ASA in this cohortSDH = 2.0Relative risk of bleeding on A/CICH = 2.0; SDH = 4.0

For 1000 patients with lobar ICH, A/C would result in 31 fewer thromboembolic events, but 150 additional ICHs

Conclusions:A/C not indicated after lobar ICHA/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 2003If no anticoagulation, is antiplatelet better than no treatment at all?

Case Example72 year old white man presents with expressive aphasia, headache, declining mental statusLikely spontaneousno specific hx of traumaOn ASA/PLAVIX for CADL Acute SDH (2cm) with 1cm MLS; L inferior frontal contusion/ICHUnderwent platelet tx, emergent craniotomy, evacuation of SDHPOD #1

POD 2more lethargic, worse expressive aphasia (contd plt tx); CT shows recurrent L frontal ICH, SDH, MLS

Redo Urgent CraniotomyPOD 4: doing well clinically, but draining scalp incision

3 wks laterwound infection/infected bone flapwound washout, craniectomy

ASA stopped (10 days prior), underwent Cranioplasty 5 months later with postop EDH (developed 12h after surgery with presentation of weak RUE, expressive aphasia)--underwent take back for evacuation

Eventually did wellsutures out (5 surgeries later)

Story doesnt end1 week later:Admitted to OSH with massive MI, resulting in resumption of ASA/PLAVIX

Antiplatelet use and ICH22071 male physicians (aged 40-84) randomly assigned to 325mg ASA or placebo qODAt 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 yrsASA 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 1991Antiplatelet use and ICHMeta-analysis of 16 RCTs on ASA useInternational study of 55462 participantsRR reduction of MI with ASARR reduction of ischemic stroke with ASARR increase in hemorrhagic stroke with ASA (84% increased RR)(all three were significant at P