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?