Reversing AnticoagulationIn Intracerebral Hemorrhage
John PerezOctober 27, 2015
Today’s outline:
The Basics
There are 4 steps to hemostasis
The coagulation cascade is a result of complex interactions between factors
aPTT PT/INR
The body balances anticoagulation and procoagulation
Procoagulation
Anticoagulation
I, II
III, IV
V, VI, VII, VIII
IX, X, XI, XIIC, S,
Antithrombin, Plasmin
Diseases upset the body’s balance
Procoagulation
AnticoagulationAF, MI, DVT Heart Valves
Dyscracias
Embolisms
Stroke
Different drugs are used to restore balance
Procoagulation
WarfarinHeparin
Anti-PlateletsNOACs
AF, MI, DVT Heart Valves
Dyscracias
Embolisms
Stroke
Anticoagulation
But too much drugs is a problem, too
Procoagulation
Anticoagulation
Disease
Anti-Platelets
Heparin
Warfarin
NOACs
II. The Problems
Anticoagulants have potential risks for bleeding
Intracerebral hemorrhage has several etiologies
Anticoagulation is double-bladed
Anticoagulation
Problems:1.Mortality rates2.INR range
Infarct Hemorrhage
Aspirin was most frequently used in a cohort of 435 ICH patients
Rosand et al. “The Effect of Warfarin and Intensity of Anticoagulation on Outcome of ICH.” Stroke. 2004
57/MTricycle driver
HTNCAD s/p MI
AFMR
On warfarinINR 2.6
Mr. CU came in for loss of consciousness
III. The SolutionsWarfarin, Heparin and Special Cases
Goals of Emergent Management
1. Aggressively lower INR to normal2. Aggressive BP control3. Ventriculostomy if indicated4. For rFVIIa: monitor ECG, troponins5. For FFP: monitor for congestion
Wijdicks and Rabinstein. Neurocritical Care. 2012
Management will rely on the underlying drug
Reversing Warfarin
Warfarin inhibits Vitamin K-dependent factors: II, VII, IX, X
Vitamin K and FFP are used to reverse warfarin
10mg IV
15-20mL/kgover 90 minutes
Hemphill et al. “Guidelines for Management of Spontaneous ICH.” Stroke. 2015
All clotting factors, anticoagulants, fibrinogen, proteins, electrolytes
Vitamin K and FFP have pros and cons
Vitamin K FFP
Onset of Action Slow; depends on liver function Fast
Time to Prepare Fast Slow
Volume Required Little Plenty
Risks AnaphylaxisInfection, anaphylaxis, transfusion reactions,
congestion
Wijdicks and Rabinstein. Neurocritical Care. 2012
PCC and rFVIIa are acceptable alternatives
25-50 units/kg
20-40mcg/kg
Wijdicks and Rabinstein. Neurocritical Care. 2012
II, VII, IX, X, C, S
rVIIa induces activation of the extrinsic pathway
PCC and rVIIa have advantagesVitamin K FFP PCC rVIIa
OnsetSlow;
depends on liver function
Fast Fast
Time to Prepare Fast Slow Fast
Volume Required Little Plenty Little
Risks Anaphylaxis
• Infection• Anaphylaxis• Transfusion
reactions• Congestion
• Expensive• Not widely available
• Not extensively studied
• Myocardial Infarction
Wijdicks and Rabinstein. Neurocritical Care. 2012
Close monitoring of INR is essential
Torbey. Neurocritical Care. 2012
ReversingHeparin
Heparin indirectly inhibits IIa and Xa
Heparin
Protamine sulfate renders heparin inert
1mg per 100 units heparinFor LMWH: 1mg/1mg LMWH
Interval (mins)
Dose (mg/100u heparin)
30-60 0.5-0.75
60-120 0.375 – 0.5
> 120 0.25 to 0.375
SIVP max rate of 5mg/minMax dose: 50mg
Hemphill et al. “Guidelines for Management of Spontaneous ICH.” Stroke. 2015
Special Case 1: Platelet Disorders and Aspirin in ICH
Broderick et al. “Guidelines for Management of Spontaneous ICH in Adults.” Stroke. 2007
Broderick et al. “Guidelines for Management of Spontaneous ICH in Adults.” Stroke. 2007
Special Case 2: ICH after fibrinolytics
• Poor prognosis• Platelet transfusion• Cryoprecipitate • Fibrinogen• VIII, XII• vWF
Emergent reversal creates a new problem
Anticoagulation
Therapeutic HemorrhageInfarct
The decision to restart anticoagulation demands a hollistic assessment
Broderick et al. “Guidelines for Management of Spontaneous ICH in Adults.” Stroke. 2007
Evaluate risk for:• DVT• PE• MI• Repeat ICH• Overall neurologic status
700mL FFP
How did we manage Mr. CU?
10mg IV q6 x 4 doses
INR2.6 1.2 in 24 hours
What happened to Mr. CU?
• 2nd HD: underwent bilateral ventriculostomy– Serial CT showed persistence of hydrocephalus
• Warfarin put on hold. – INR trend: 2.6 1.21 1.0
• 9th HD: underwent VP shunting• 19th HD: family opted to THOC
Wrapping up today’s session
Questions?