Anticoagulation Reversal for Major Bleeding (ISTH 2025)

Algorithm Steps

1. ▶

   Start

   Major Bleeding on Anticoagulant

   Life-threatening or critical site bleeding requiring reversal

   1. ◆

      Decision

      Identify Anticoagulant

      Which anticoagulant is the patient taking?

      1. ●

         Action

         Warfarin (VKA)

         Vitamin K antagonist reversal

         • Check INR
         • 4-Factor PCC 25-50 units/kg (based on INR)
         • Vitamin K 10mg IV slow infusion
         • Recheck INR in 30 min
         • Target INR <1.5
         1. ●

            Action

            Supportive Care (All Patients)

            Standard hemorrhage management

            • Hold anticoagulant
            • IV access, type and screen
            • Transfuse PRBCs for hemodynamic instability
            • Consider platelets if plt <50k
            • Local hemostatic measures
            • Maintain normothermia
            1. ◆

               Decision

               Bleeding Site

               Location-specific considerations

               1. ⚠

                  Warning

                  Intracranial Hemorrhage

                  Most urgent - rapid reversal critical

                  • Door-to-reversal time critical
                  • Target SBP <140 mmHg
                  • Neurosurgery consultation
                  • Repeat CT in 6 hours
                  • ICU admission
                  1. ●

                     Action

                     Reassess Response

                     Check hemostasis and labs

                     • Clinical bleeding assessment
                     • Repeat coagulation studies
                     • Consider re-dosing if ongoing bleeding
                     • Plan anticoagulation resumption timing
                     1. ✓

                        Outcome

                        Bleeding Controlled

                        Plan for anticoagulation resumption based on indication

               2. ●

                  Action

                  GI Hemorrhage

                  Endoscopy when stable

                  • IV PPI (pantoprazole 80mg bolus)
                  • Gastroenterology consultation
                  • Endoscopy within 24h (or emergent if unstable)
                  • Transfuse to Hgb >7 (>8 if CAD)
               3. ●

                  Action

                  Other Major Bleeding

                  Muscle, retroperitoneal, etc.

                  • Imaging to characterize
                  • Surgical/IR consultation as needed
                  • Embolization if appropriate
                  • Compartment syndrome monitoring
      2. ●

         Action

         Dabigatran

         Direct thrombin inhibitor reversal

         • Idarucizumab 5g IV (2x2.5g vials)
         • Full reversal within minutes
         • Can re-dose if needed
         • If unavailable: 4F-PCC 50 units/kg
         • Hemodialysis removes ~60% in 2-3h
      3. ●

         Action

         Factor Xa Inhibitors

         Apixaban, rivaroxaban, edoxaban

         • Andexanet alfa if available:
         • Low dose: 400mg bolus + 4mg/min x2h
         • High dose: 800mg bolus + 8mg/min x2h
         • If unavailable: 4F-PCC 50 units/kg
         • TXA 1g IV as adjunct