Guidelines for reversal of antithrombotics in intracranial hemorrhage

Neurocritical Care Society and Society of Critical Care Medicine just published guidelines for the reversal of antithrombotics in intracranial hemorrhage.

Summary is here in this table.



Antithrombotic agent Reversal agent
Vitamin K antagonists If INR more than 1.4


vitamin K 10 mg IV,

plus 3- or 4-factor PCC IV (dosing based on weight, INR, and PCC type) (Strong recommendation)or

fresh frozen plasma 10-15 mU kg IV if PCC not available


Direct factor Xa inhibitors Activated charcoal (50g) within 2 hr of ingestion, activated PCC (FEIBA) 50 U/kg IV or 4-factor

PCC 50 U/kg IV


DTis For dabigatran reversal:


Activated charcoal (50g) within 2 hr of ingestion, and idarucizumab 5g IV (in two 2.5 gm/ 50 ml vial) Consider hemodialysis or idarucizumab redosing for refractory bleeding after initial administration

For other DTis:

Activated PCC (FEIBA) 50 U/kg IV or


4-factor PCC 50 U/kg IV


Unfractionated heparin Protamine 1 mg IV for every 100 units of heparin administered in the previous 2-3 hr (up to 50 mg in a single dose)


LMWHs Enoxaparin:


Dosed within 8 hr: protamine 1 mg IV per 1mg enoxaparin (up to 50mg in a single dose) Dosed within 8-12 hr: protamine 0.5 mg IV per 1 mg enoxaparin (up to 50mg  in a single dose) Minimal utility in reversal> 12hr from dosing

Dalteparin,nadroparin, and tinzaparin:


Dosed within 3-5 half-lives of LMWH: protamine 1 mg IV per 100 anti-Xa units of LMWH (up to 50 mg in a single dose) or


rFVIIa 90 pg/kg IV if protamine is contraindicated


Danaparoid rFVIIa 90 pg/kg IV


Pentasaccharides Activated PCC (FEIBA) 20 U/kg IV or rFVIIa 90 f.lg/kg IV


Thrombolytic agents

(plasminogen activators)



Cryoprecipitate 10 units IV or antifibrinolytics (tranexamic acid 10 -15 mg/kg IV over 20min or  alpha- aminocaproic acid 4-5g IV) if cryoprecipitate is contraindicated


Antiplatelet agents Desmopressin 0.4 mcg/kg IV x 1


If neurosurgical intervention: platelet transfusion (one apheresis unit)








Few more points


  1. They recommend against VKA reversal in patients where there is a high suspicion of intracranial hemorrhage due to cerebral venous thrombosis (Conditional recommendation, very low quality evidence).
  2. They recommend assessing risks and benefits when considering VKA reversal in intracranial hemorrhage patients with concurrent symptomatic or life-threatening thrombosis, ischemia, heparin-induced thrombocytopenia, or DIC (Good Practice statement).
  3. They recommend against administration of rFVIIa or FFP in DTI-related intracranial hemorrhage
  4. They recommend against protamine for reversal of pentasaccharides
  5. In intracranial hemorrhage patients receiving pentasaccharides for venous thromboembolism prophylaxis, we suggest against reversal unless there is evidence of bioaccumulation or impaired clearance (Good Practice statement).
  6. They recommend platelet function testing prior to platelet transfusion if possible (Strong recommendation, moderate quality evidence).


















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