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Antithrombotic medication reversal in traumatic brain injury (TBI) is a nuanced topic, requiring assessments of injury severity, appropriate reversal agent and dosing strategy, and potential risks to the patient.

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Written by Michael Stocker

Besting bleeding blood-thinned brains
We frequently treat TBI in the setting of antithrombotic use; yet, determining when and how to handle reversal can be cause for consternation. This comprehensive review breaks it down:

• What determines “active antithrombotic therapy”?

  • Treatment with vitamin K agonist plus INR >1.5, direct oral anticoagulant (DOAC) within 24 hours, or antiplatelet agent (APA) within 5 days.
  • These patients warrant CT head, platelet count, and INR at minimum.

• Patients most likely to need surgical intervention or at risk of hemorrhage progression should be considered for reversal:

  • GCS ≤ 12, subdural hematoma (SDH) ≥ 8mm, mixed density chronic SDH, intraparenchymal hemorrhage (IPH) ≥ 2cm, multifocal IPH, or midline shift ≥ 5mm

• APA (aspirin, clopidogrel, prasugrel, ticagrelor) reversal with platelet transfusion carries significant risks and is generally not recommended. It may be considered immediately preceding operative intervention in select cases. Desmopressin lacks evidence here thus routine use is not recommended.
• Reversal of specific agents:

  • Unfractionated heparin: protamine 1mg IV per 100 U of heparin within preceding 2-3 hours, up to 50mg. Elevated aPTT guides repeat dosing.
  • Low-molecular weight heparin (LMWH): If last dose within 8 hours, protamine 1mg IV per 1mg LMWH. If within 8-12 hours, protamine 0.5mg IV per 1mg LMWH. If ≥12 hours, consider reversal in presence of renal impairment.
  • Vitamin K antagonists: Co-administration of 4-factor prothrombin complex concentrate (4FPCC) and vitamin K IV is preferred. Fixed dosing of 4FPCC at 1500-2000 IU has shown faster administration and higher likelihood of hemostasis compared to weight- and INR-based protocols.
  • DOAC (apixaban, rivaroxaban, edoxaban): While 4FPCC is “off-label”, consider 2000 IU or 25-50 IU/kg.

    • Dabigatran: Idarucizumab, if available, 5g IV administered in two equal doses < 15 minutes apart.

• Note that since this article’s publication, andexanet alfa has been removed from the US market thus recommendations regarding this drug have been left out here.

How will this change my practice?
With andexanet alfa out, 4FPCC will be my go-to in most anticoagulated cases warranting reversal. TBI patients can rarely provide an accurate last dose time, so I’ll continue to image liberally and consult closely with neurosurgery when significant ICH is present. I’ll defer platelet transfusion for APA reversal unless otherwise prompted by the surgeon in operative cases.

Source
Reversal of antithrombotic medications in patients with traumatic brain injury: What you need to know. J Trauma Acute Care Surg. 2025 Dec 1;99(6):828-835. doi: 10.1097/TA.0000000000004766. Epub 2025 Aug 19. PMID: 40828405.