Neurocritical Care

Anticoagulant

Reversal Agent and Dose

Adverse Effects

Warfarin

4F-PCC [INR < 4 (25 units/kg, max 2500 units), INR

4–6 (35 units/kg, max 3500 units), INR > 6 (50

units/kg, max 5000 units)] + vitamin K 10 mg IV

Alternative: FFP 10–15 mL/kg + vitamin K 10 mg IV

Thrombosis, anaphylactoid reaction,

(vitamin K), pulmonary edema, or

transfusion-related reaction (FFP),

contains heparin (4F-PCC)

PO factor Xa

inhibitors

(rivaroxaban,

apixaban)

Andexanet alfa (Andexxa) (see dosing information

that follows in Table 12)

or 4F-PCC 25–50 units/kg

or activated 4F-PCC (FEIBA) 25–50 units/kg

Andexanet

Thrombosis; limited data for reversal,

especially with FEIBA

PO DTIsa

(dabigatran)

Idarucizumab (Praxbind) 5 g IV × 1; repeat dose may

be necessary in patients with high DTI exposure or

poor renal function

Thrombosis; limited data analyses

show minimal efficacy for reversal

with PCC and FEIBA

PO antiplatelets

Platelet transfusion infusion (usefulness is uncertain

– see Neurocrit Care 2016;24:6-45)

Consider desmopressin 0.4 mcg/kg IV

Pulmonary edema or transfusion-

related reaction

Unfractionated

heparin

Protamine 1 mg (max 50 mg) for each 100 units of

heparin (infused within the past 2–3 hr)

Hypotension, hypersensitivity

Low-molecular-

weight heparins

Protamine 1 mg (max 50 mg) for each 1 mg of enoxa-

parin (within 8 hr of last dose)

Hypotension, hypersensitivity

aReversal options have not been tested in patients with ICH and have had varying degrees of coagulopathy reversal in experimental animal and human models.

DTI = direct thrombin inhibitor; FEIBA = factor eight inhibitor bypassing activity; FFP = fresh frozen plasma; 4F-PCC = 4-factor prothrombin complex concentrate.

Factor Xa Inhibitor

Last Dose

< 8 hr or Unknown Since Last Dose

≥ 8 hr Since Last Dose

Apixaban

≤ 5 mg

> 5 mg or unknown

Low dose

High dose

Low dose

Rivaroxaban

≤ 10 mg

> 10 mg or unknown

Low dose

High dose

Low dose = 400 mg at a target rate of 30 mg/min, then 4 mg/min for up to 120 min; high dose = 800 mg at a target rate of 30 mg/min, then 8 mg/min for up to 120 min.

Blood Pressure Management

Prompt control of blood pressure is essential.

Historically, caution may have been used in rapidly reducing blood pressure in patients with chronic

hypertension because of concerns regarding accommodations in cerebral autoregulation.

However, there may be some benefit of rapidly reducing the blood pressure to approximately 140-

150 mm Hg (and thus reducing the risk of hemorrhage expansion). This may outweigh concern for

cerebral autoregulation issues and potential for ischemia, but patients with initial SBP >180 mm Hg

may have a greater risk of renal dysfunction.

hour (N Engl J Med 2013;368:2355-65). SBP less than 140 mm Hg was as safe and effective as SBP

less than 180 mm Hg (and may have improved functional outcomes).

ATACH-2 – Large, prospective, randomized trial comparing blood pressure control within 4½

hours in patients with SBP >180 mm Hg. Targeting an SBP goal of 110–139 mm Hg was as effective

as targeting an SBP goal of 140–179 mm Hg but was associated with increased renal adverse events

at 3 months. (Mean minimum SBP in the first 2 hours after randomization was 128.9 mm Hg in

the intensive-treatment group and 141.1 mm Hg in the standard-treatment group.) (N Engl J Med

2016;375:1033-43).