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Stroke prophylaxis in an atrial

fibrillation patient with chronic

subdural hematoma – a

double-edged sword

Adam Mah, LMPS resident

SPH/LGH Pod

October 12th, 2017

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Learning objectives

• Critically appraise the literature for OAC

for patients with history of chronic subdural

hematoma and atrial fibrillation (AF)

• Weigh the benefits and risks of OAC in a

patient with non-valvular A-fib and history

of chronic subdural hematoma

• Compare and contrast anticoagulation

strategies for an inpatient with AF and

history of chronic subdural hematoma

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ID BW, 87 yo female admitted Sept 20th to PIMS,

transferred to CTU on Sept 26th

C/C Back pain

HPI Slipped and fell while using walker, found down

but conscious by son in bathroom

PMHx - TIA (2008) - CAD - Hypothyroidism

- Paroxysmal AF - COPD - Chronic constipation

- Recurrent falls, last 2016 - HTN

- Chronic subdural hematoma (~2008)

- Pacemaker for 2nd degree heart block

FHx Non-contributory for CV risk and osteoporosis

SHx Lives in residential care, no smoking, no EtOH,

no illicits

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Vitals BP 160/80, HR 70, RR 20 (90% 2L NP), temp

not documented now RR 16 saturating 94%

on RA

CNS/Psyc AAOx3, GCS 15 delirious last HS, not easily

rousable

HEENT Pt refused full exam in ED

Resp Chest clear to ascultation, no wheezes

CV Pt refused full exam in ED. CHADS2 = 4

GI Exam normal

GU JVP not observed. No CVA tenderness

Endo Not thirsty; A1c 5.6% (Sept 20)

Heme No bruising, no hemoptysis or hematemesis

MSK 7-9/10 pain to lumbar spine region (L3 to L4)

Derm Unremarkable

Allergies NKDA

Labs and diagnostics • Admission (current)

– Na 140 (133), K 4.6 (4.2), SCr 104 (118), eGFR 42 (36),

CrCl 30 (27)

– INR 2.7 (1.2), albumin 32 (24), lactate 0.8

– NT-pro-BNP 3155, troponin 39, QTc 607 ms

– TSH 0.31, A1c 5.6, random BG 6.5

• CT head: chronic subdural hematoma that

is “stable and hasn’t grown”, no acute

changes. CT spine: compression fracture

• Dx: vertebral fracture secondary to

mechanical fall

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Held home

medications

Continued home

medications

Warfarin 4 mg PO daily Melatonin 3-6 mg PO 2 hrs

before HS

Amlodipine 2.5 mg PO

daily

Vitamin D 10 000 units PO

weekly on Wednesdays

Perindopril 2 mg PO daily L-thyroxine 137 mcg PO daily

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Medications in hospital

Sufentanil 12.5-25 mcg SL/SC 30

mins before turns (max 4

doses/day)

Ipratropium 0.5 mg nebs QID and q4h PRN

Salbutamol 2.5 mg nebs QID and q4h PRN

Ca carbonate 1250 mg PO daily with food

PEG 17 g PO daily

Lactulose 30 mL PO daily

Bisacodyl 10 mg PO daily HS

Sennosides 8.6-17.2 mg PO HS PRN

Hydromorphone 0.25 mg PO BID

Acetaminophen 975 mg PO/PR QID

ASA 81 mg PO/325 mg PR daily

Atorvastatin 80 mg PO daily

Captopril 12.5-25 mg SL q30min PRN SBP

>220

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DTPs – BW is…

1. At risk of recurrent cardiogenic ischemic stroke

secondary to not receiving anticoagulation

2. At risk of VTE secondary to not receiving

anticoagulation prophylaxis while in hospital

3. At risk of recurrent ischemic stroke secondary

to not receiving antihypertensive therapy

4. At risk of barrier to discharge secondary to

receiving nebulized ipratropium

5. At risk of barrier to discharge secondary to

receiving nebulized salbutamol

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Goals of therapy

• Minimize risk of cardioembolic stroke

• Minimize expansion of chronic subdural

hematoma

• Avoid neurological sequelae

• Minimize adverse drug reactions

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Where does a subdural

hematoma (SDH) occur?

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http://www.primehealthchannel.com/wp-content/uploads/2011/02/Subdural-Hematoma-photos.jpg

Are all ICHs made equal?

• SDH = Usually from head injury, mix of

serous fluid and clotted blood1

• Lobar ICH = Higher risk of re-bleed on

anticoagulants2

• Symptoms = decreasing cognition,

headaches1

• As time progresses, risk of clot goes up

and risk of bleed goes down2

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Guidelines for ICH and

resumption of anticoagulation • AHA/ASA3: After non-lobar ICH, may be

considered if “strong indication”

– Avoid anticoagulants for >4 weeks

• Canada4: Decision whether to restart on “case-

by-case” basis. Evidence unclear regarding

timing

• ESO (Europe)5: “In the absence of

RCTs…cannot make firm recommendations…”

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Treatment alternatives

• No anticoagulation

• Antiplatelet: ASA and/or clopidogrel

• Re-initiate warfarin

• Factor Xa inhibitors

– Rivaroxaban

– Edoxaban

– Apixaban

• Dabigatran

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PICO

P Patients with indication for

anticoagulation but have suffered

subdural hematoma

I Anticoagulation or antiplatelet

C Anticoagulation, antiplatelet, or placebo

O Mortality, recurrent ICH, recurrent

ischemic stroke, disability, bleed

requiring hospitalization

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Search strategy and results

• PubMed, Medline

• [exp Hematoma, Subdural] AND [Stroke or

Atrial Fibrillation or Warfarin] AND

[Anticoagulation]

• Clinical trials, cohort studies, observational

studies

• 2 prospective observational, 1 single-arm

prospective trial

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De Vleeschouwer et al.6 Design Single-centre prospective observational study

Patient

population

N = 108

Patients admitted Jun 1993-Dec 2000 with ICH

- 28 had subdural hematoma (SDH), 56 had non-

valvular A-fib (most common OAC indication)

- Median INR upon admission = 3.7

Outcomes If OACs were restarted, occurrence of thromboembolic

event (TE: stroke or VTE), recurrent ICH

Results

(n = 25 for

restarting

OAC)

- Median time to restarting OACs = 11 days

- 0/25 pts who restarted had TE

- 8/81 pts who did not restart had TE.

- 3 dead, 5 severely disabled.

- No SDH in non-restarters

- Of those with SDH who experienced recurrent

SDH while on OAC, 3 out of 4 made a good

recovery

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De Vleeschouwer et al.6

Conclusions More prospective research

needed for late management

Criticisms - Enoxaparin started in all for

inpatient VTE prophylaxis

- Confounding by indication:

majority had prosthetic valves

- Heterogeneous population

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Claassen et al.7

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Design Single-centre prospective observational study

Patient

population

N = 48

-Patients admitted Nov 2001-Dec 2005 for warfarin-

associated ICH (WAICH)

- Most ICHs were lobar in nature

- Avg age 70.8 in restarted arm, most had comorbid A-fib

and HTN.

- Counted as “restarted” if <60 days from ICH.

Outcomes Mean follow-up = 43 months. Recurrent non-traumatic

WAICH, traumatic ICH, extracrainal hemorrhage,

thromboembolic stroke, PE, distal arterial embolus.

Results

(n = 23 for

restarting

OAC)

OAC no OAC

- Thromboembolic stroke: 0/23 vs. 3/25

- VTE: 0/23 vs. 2/25

- Traumatic ICH: 2/23 vs. 0/25

- GI hemorrhage: 2/23 vs. 2/25

Claassen et al.7

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Conclusions WAICH uncommon with resumption.

Defer to clinical judgement. Lobar ICH:

not resuming warfarin may result in

VTE, but risk of traumatic ICH not zero.

Criticisms - No documentation whether pts

were on antiplatelets

- Did not mention if VTE prophylaxis

was utilized

- Did not reach statistical

significance

- Only patients where warfarin was

suspected cause for ICH

Yeon et al.8

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Design Prospective single-arm, single-centre trial

Patient

population

N = 20

- Patients admitted Feb 2008-Apr 2010 for burr hole

drainage

- Had warfarin +/- antiplatelets, chronic or acute SDH,

and an INR of >1.5 upon presentation .

- Warfarin restarted 3 days after

- Mean CHADS2 = 2.1; mean INR = 2.64

Outcomes Regular INR monitoring and brain CT scans

Results - Recurrent SDH documented by CT head within a

month of surgery = 3/20

- Any other ICH = 0/20

- Extracrainal hemorrhage within 6 mos = 0/20

- Ischemic stroke/TIA/VTE within 6 mos = 0/20

Yeon et al.8

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Conclusions Restarting warfarin therapy can

be done 3 days post-op for SDH.

Begs a comparative trial for

warfarin resumption post-burr

hole drainage

Criticisms - Target INR in study was 1.7-2.5

- CHADS2 only validated in A-fib

patients = 25% pts in trial

- No comparator group and only

included surgery pts

Summary of evidence

Study Days to

restart OAC

from ICH

Strokes

and VTE

Recurrent

ICH

De Vleeschouwer

et al (2005)

Median 11 ↓* ↑*, but ↓

disability

Claassen et al

(2008)

<60 ↓* ↑*

Yeon et al (2012) 3 0/20 3/20

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Recommendation/rationale

• Recommend D/C ASA PO and supps

• Recommend start warfarin 4 mg PO daily, INR

target 2-2.5, INR to be taken day 3 after initiation

• Recommend start dalteparin 5000 units SC BID

for at least 5 days, D/C when INR is 2-2.5

• Warfarin toxicity reversible

• Only case reports exist for NOACs

– ARISTOTLE9 cannot be applied – subgroup analysis NNT 434 for ↓ICH, 1.5% of pts had

CrCl <30 mL/min

• CrCl >20 mL/min, no need for heparin

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Monitoring plan Parameter Change When

INR ↑ to 2-2.5 3 days

Heart rate Keep at 60-110 bpm Ongoing daily

Arrhythmias Subjective sensation of palpitations,

room spinning

Ongoing daily

Blood pressure Decrease to <150/90 mm Hg Ongoing daily

ICH Presence of FAST symptoms,

headache or cognitive changes from

baseline

Twice daily

Cardiogenic

ischemic stroke

Presence of FAST symptoms Twice daily

Bleeding from

gums, rectum

Presence of bleeding gums, BRBPR,

coffee ground stools/emesis

Ongoing daily

VTE Hemoptysis, SOB, unilateral leg

swelling/tenderness

Ongoing daily

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Actual course in hospital

• Recommendation not accepted

• CNS: Suffered left MCA ischemic stroke in

hospital, did not receive alteplase

– Neuro opinion = wait 2 weeks f/u CT to rule

out hemorrhagic transformation then start

apixaban for cardiogenic stroke prophylaxis

• Psyc: Had delirium/agitation: loxapine

1.25 mg PO/SC q4h PRN added – good

effect currently conversing normally

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Actual course in hospital

• MSK: Pain well controlled (does not

require regular hydromorphone anymore)

• GI: Baseline bowel function from

residential care unknown; bowels regular

in hospital on regular PEG and lactulose

• Dispo: Transferred back to PIMS

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Resolution of other DTPs

• Recommend re-initiating amlodipine 2.5 mg PO

daily – implemented

• Recommend D/C ipratropium and salbutamol

nebs – implemented

• Recommend ipratropium 40 mcg (2 puffs)

inhaled QID regular via aerochamber -

implemented

• Recommend salbutamol 200 mcg (2 puffs)

inhaled q1h PRN SOB via aerochamber -

implemented

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References 1. Sahyouni R, Goshtasbi K, Mahmoodi A et al. Chronic Subdural Hematoma: a Historical and

Clinical Perspective. World Neurosurg 2017;S1878-8750(17):31571-1.

2. Goldstein JN, Greenberg SM. Should anticoagulation be resumed after intracerebral

hemorrhage? Cleve Clin J Med 2010;77(11):791-99.

3. Hemphill JC, Greenberg SM, Anderson CS et al. Guidelines for the Management of

Spontaneous Intracerebral Hemorrhage. Stroke 2015;46(7):2032-60.

4. Casaubon LK, Boulanger JM, Blacquiere D et al. Canadian Stroke Best Practice

Recommendations: Hyperacute Stroke Care Guidelines, Update 2015. Int J Stroke

2015;10(6):924-40.

5. Steiner T, Salman RA, Beer R et al. European Stroke Organisation (ESO) guidelines for the

management of spontaneous intracerebral hemorrhage. Int J Stroke 2014;9(7):840-55.

6. De Vleeschouwer S, van Calenbergh F, van Loon J et al. Risk Analysis of Thrombo-embolic

and Recurrent Bleeding Events in the Management of Intracranial Haemorrhage Due to Oral

Anticoagulation. Acta Chirugica Belgica 2005;105(3):268-74.

7. Claassen DO, Kazemi N, Zubkov AY et al. Restarting Anticoagulation Therapy After Warfarin-

Associated Intracerebral Hemorrhage. Arch Neurol 2008;65(10):1313-18.

8. Yeon JY, Kong DS, Hong SC et al. Safety of Early Warfarin Resumption following Burr Hole

Drainage for Warfarin-Associated Subacute or Chronic Subdural Hemorrhage. Journal of

Neurotrauma 2012;29:1334-1341.

9. Granger CB, Alexander JH, McMurray JJV et al. Apixaban versus Warfarin in Patients with

Atrial Fibrillation. NEJM 2011;365(11):981-92.

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Questions?

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Appendix – patient

characteristics

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De Vleeschouwer et al.6

• n = 73 for intraparenchymatous hematoma

(thalamic, cerebelllar, basal ganglionic)

• n = 28 for subdural hematoma

• n = 6 for intraventricular bleed

• n = 1 for subarachnoid hemorrhage

• 77/108 had supratherapeutic INR (≥3)

upon admission

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Claasen et al.7

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Yeon et al.8

• Avg age = 65.1

• Indications for warfarin

– Afib = 15 (10 of which had mechanical valves)

– Mitral stenosis = 1

– Femoral vascular graft = 1

– Cerebellar infarction = 1

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