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Hematology · Emergency dosing

Anticoagulant reversal

Adults only. Major bleeding, intracerebral hemorrhage or urgent surgery on an anticoagulant or antiplatelet drug: what reverses it, the label or guideline dose with its cap, whether the last dose is recent enough to matter, and what not to give. Andexanet alfa is no longer sold in the US.

Kcentra by INR band, cappedDOAC timing by half-lifeNo andexanet in the USReviewed Oct 2026

1What is the patient taking?

2Situation

Adults only: Kcentra, Balfaxar, Praxbind and protamine are not studied or not established in children. In pregnancy the labels say to give these products only if clearly needed; obstetric hemorrhage is out of scope. First option (ACC 2020): hemodynamic instability, a life-threatening bleed, a bleed not controlled by local measures and resuscitation, or a critical site — intracranial (including traumatic, subdural, epidural and subarachnoid), intraocular, spinal, pericardial, airway (including posterior epistaxis), hemothorax, intra-abdominal, retroperitoneal, intramuscular or intra-articular. Intraluminal GI bleeding is not a critical site. Major: overt bleeding with a hemoglobin drop of 2 g/dL or more, or 2 or more units of red cells. Spontaneous ICH uses the AHA/ASA 2022 guideline; for other intracranial bleeding choose the first option, then “Intracranial”.

3Patient and labs

4Contraindication screen

Suspected HIT now? 4Ts score (opens in a new tab)

How it works

Dose rules used
AgentRuleSource
4F-PCC for warfarinINR 2 to under 4: 25 units/kg, max 2,500. INR 4 to 6: 35 units/kg, max 3,500. INR over 6: 50 units/kg, max 5,000. Dosing weight capped at 100 kg. Rate 0.12 mL/kg/min (about 3 units/kg/min), max 8.4 mL/min. No repeat dose.Kcentra label; Balfaxar label (urgent surgery only)
4F-PCC fixed dose, warfarin1,000 units for a non-intracranial major bleed (shown at INR 2 or more); 1,500 units for any intracranial bleed (shown at INR 2 or more, and at INR 1.4 or more — or 1.3 to 1.9 in spontaneous ICH — alongside the 10–20 IU/kg dose)ACC ECDP 2020, Figure 3
4F-PCC, warfarin intracranial bleed, INR under 210–20 IU/kg (off-label), with the label’s 100 kg dosing-weight cap. Spontaneous ICH: INR 1.3 to 1.9 (AHA/ASA 2022 #4). Any intracranial bleed: INR 1.4 or more (NCS/SCCM 2016 VKA rec 4: PCC rather than FFP). ECDP fixed 1,500 units also shown (no INR band in ECDP Figure 3). Monitoring: INR 15–60 min after PCC, then every 6–8 h for 24–48 h; INR still 1.4 or more: vitamin K 10 mg IV again and consider FFP; no repeat PCC.AHA/ASA 2022; NCS/SCCM 2016 VKA recs 3–4; ECDP 2020
Vitamin K5–10 mg IV for a major bleed or ICH on a VKA (no INR threshold in ECDP Figure 2); 2–5 mg orally or IV may be considered for a non-major bleed needing admission. IV no faster than 1 mg/min.ECDP 2020; AHA/ASA 2022 #3; phytonadione label
Plasma10–15 mL/kg only when 4F-PCC is not available. The tool shows it only at INR 2 or more (the tool’s own conservative choice; ECDP Figure 3 sets no INR band), except intracranial bleeding with PCC contraindicated and INR 1.4 or more: FFP 10–15 mL/kg with vitamin K 10 mg IV (NCS/SCCM 2016 VKA rec 6, conditional).ECDP 2020, Figure 3; NCS/SCCM 2016
4F-PCC, factor Xa inhibitor2,000 units fixed, severe or life-threatening bleeding (off-label)ECDP 2020, section 5.6.3
Idarucizumab5 g IV (two 2.5 g vials); a second 5 g only for recurrent bleeding with raised clotting tests or a second urgent procedurePraxbind label
PCC or aPCC, dabigatran50 units/kg, max 4,000 units, if idarucizumab is unavailable (off-label)ECDP 2020, section 5.6.2
DOAC timingHalf-life from ECDP Table 4A (dabigatran by CrCl; factor Xa inhibitors by agent and CrCl, never below 15 h). 3 half-lives or fewer: dose shown. Over 3 to 5: dose with a check-a-level caveat. Over 5: no reversal dose — except dabigatran with CrCl under 30 or dialysis (NCS/SCCM 2016 DTI rec 5b: renal insufficiency prolongs exposure) and factor Xa inhibitors with liver failure in intracranial bleeding (NCS/SCCM 2016 FXa rec 5). Loading-phase dosing or overdose beyond 5 half-lives: no automatic dose; check a calibrated anti-Xa level; both keep the caveat. Unknown time: treated as within the window, with the caveat. GI bleeding also needs a dose in the past 24 h (ACG-CAG 2022; ACG 2023).ECDP 2020; NCS/SCCM 2016
Protamine, UFHIV heparin only: 1 mg per 100 units given in the previous 2–3 h; max single dose 50 mg; no more than 50 mg in any 10 min. If the aPTT stays high: 0.5 mg per 100 units. SC prophylactic heparin: not reversed routinely; consider it only if the aPTT is significantly prolonged. SC therapeutic heparin: the IV formula does not apply; no dose shown. Boxed warning on every line.NCS/SCCM 2016; heparin and protamine labels
Protamine, enoxaparinTreatment dose. Within 8 h: 1 mg per 1 mg. Over 8 h: 0.5 mg per 1 mg. 12 h or more: may not be needed, but with CrCl under 30 or persistent life-threatening bleeding NCS suggests redosing 0.5 mg per 1 mg. Unknown time: treated as within 8 h (tool choice). Second 0.5 mg per 1 mg if the aPTT 2–4 h later is still prolonged. Anti-Xa neutralized at most about 60%. Prophylactic dose with intracranial bleeding: no reversal (NCS good practice statement).Lovenox label section 10; 50 mg cap from protamine label and NCS/SCCM 2016
Argatroban, bivalirudinStop the infusion; no antidote (labels). Intracranial bleed within 3–5 half-lives: aPCC (FEIBA) or 4F-PCC 50 U/kg is an option (NCS/SCCM 2016 DTI rec 6, conditional) unless the FEIBA or Kcentra label rules it out; no rFVIIa or FFP (DTI rec 9, strong).Argatroban and bivalirudin labels; NCS/SCCM 2016
FondaparinuxNo antidote; not protamine. Treatment dose with intracranial bleeding: aPCC 20 IU/kg (NCS/SCCM 2016, conditional), or rFVIIa 90 mcg/kg if aPCC is unavailable or contraindicated — not with DIC or recent thrombosis (NovoSeven boxed warning and §5.1). Prophylactic dose: no reversal unless it has accumulated.Arixtra, FEIBA and NovoSeven RT labels; NCS/SCCM 2016
Activated charcoal, 50 gApixaban, rivaroxaban, edoxaban: within 4 h (spontaneous ICH, apixaban or rivaroxaban: possible benefit up to 8 h). Dabigatran: within 2 h. Only if intubated or at low aspiration risk. Not with unknown timing.ECDP 2020; AHA/ASA 2022 #8 text; NCS/SCCM 2016

Every band and window is judged on the number as typed (INR, hours, kg as entered or converted exactly from lb). Doses are rounded down, so a displayed dose never exceeds its cap. Fixed doses (idarucizumab, vitamin K, fixed-dose PCC) do not need weight; weight-based doses do. Plasma volumes over 1,500 mL (15 mL/kg × 100 kg) carry a large-volume warning; that threshold is the tool’s.

Restarting (ACC 2020 §5.7)

Intracranial: delay resumption for at least 4 weeks in patients without high thrombotic risk (§5.7.5). GI: reasonable to restart once hemostasis is achieved (§5.7.4). After a procedure with low bleeding risk: restart about 24 h after; higher bleeding risk: delay therapeutic doses 48–72 h (§5.7.6). High rebleeding risk with unacceptable thrombotic risk: IV unfractionated heparin, for its short half-life and protamine reversibility (§5.7.2). Restarting doses: VTE treatment.

Bleed severity (ACC 2020)

Major bleeding: a critical site, hemodynamic instability, or overt bleeding with a hemoglobin drop of 2 g/dL or more or 2 or more units of red cells. ECDP 2020 section 5.4: reversal of the anticoagulant is recommended, if an agent is available, for most patients with major bleeding — without delaying resuscitation and local hemostasis. Figure 2 reverses a major bleed that is not life-threatening and not at a critical site only if local measures and resuscitation fail to control it; vitamin K is still given for a VKA.

ICH: AHA/ASA 2022 recommendations used

Anticoagulants (5.2.1): stop and reverse as soon as possible (1, C-LD). VKA with INR 2.0 or more: 4F-PCC over FFP (1, B-R). IV vitamin K right after factor replacement (1, C-LD). INR 1.3 to 1.9: PCC may be reasonable (2b, C-LD). Factor Xa inhibitor: andexanet reasonable (2a, B-NR) — not available in the US; 4F-PCC or aPCC may be considered (2b, B-NR). Dabigatran: idarucizumab reasonable (2a, B-NR); if unavailable, PCC or aPCC (2b, C-LD) or renal replacement therapy (2b, C-LD). DOAC within the previous few hours: activated charcoal may be reasonable (2b, C-LD). UFH: protamine reasonable (2a, C-LD). LMWH: protamine may be considered for partial reversal (2b, C-LD).

Antiplatelets (5.2.2): aspirin with emergency neurosurgery: platelet transfusion might be considered (2b, C-LD). Desmopressin, with or without platelets: effectiveness uncertain (2b, C-LD). Aspirin without emergency surgery: platelet transfusion potentially harmful (3: Harm, B-R; PATCH).

NCS/SCCM 2026 focused update: 4F-PCC rather than andexanet for factor Xa inhibitors; avoid platelet transfusion in spontaneous intraparenchymal hemorrhage on antiplatelets without neurosurgery; give platelets for aspirin with surgery; no recommendation possible on desmopressin, on platelets in traumatic ICH, or on treating anticoagulant effects in small intraparenchymal hemorrhage. All conditional.

What this tool leaves out

No desmopressin dose: the 2022 AHA/ASA guideline calls its effectiveness uncertain and the 2026 NCS/SCCM update could not make a recommendation. For factor Xa inhibitors the tool shows the ECDP fixed 2,000 units only; NCS/SCCM 2016 instead suggests 4F-PCC or aPCC 50 U/kg for ICH within 3–5 half-lives or with liver failure (conditional, low quality) — not dosed here. No recombinant factor VIIa dosing (named only as the NCS alternative for fondaparinux). aPCC is named, not dosed, for fondaparinux (20 IU/kg) and IV direct thrombin inhibitors (50 U/kg). No protamine dose for subcutaneous therapeutic heparin: no source used here gives one. Other LMWHs (dalteparin) and thrombolytic bleeding are not covered; for alteplase or tenecteplase use the stroke thrombolysis tool. No protamine dose for urgent surgery on heparin and no PCC dose for urgent surgery on a factor Xa inhibitor: no source used here doses them. Andexanet alfa is listed only as unavailable. For timing elective or semi-urgent procedures, use the peri-procedural anticoagulation tool. For GI bleeding scores and restart timing, use the GI bleed tool.

Sources

  1. KCENTRA (prothrombin complex concentrate, human) US prescribing information, CSL Behring, revised 05/2023 (DailyMed setid eee1afb8-324c-42e4-8bf0-f0c9da5e6d42). Sections 1, 2.1 (Table 1), 2.3, 4, 5.2.
  2. BALFAXAR (prothrombin complex concentrate, human-lans) US prescribing information, Octapharma (DailyMed SPL effective 2023-07-21, setid 68fa4f90-8b01-6498-4140-e0be5247c3fe). Sections 1, 2, 4.
  3. PRAXBIND (idarucizumab) US prescribing information, Boehringer Ingelheim (DailyMed SPL effective 2024-01-23, setid c7400f8a-dcf4-a6df-6d07-983081b1bf34). Sections 1, 2.1–2.4, 5.2, 5.4.
  4. PRADAXA (dabigatran etexilate) capsules US prescribing information, Boehringer Ingelheim, revised 06/2025 (DailyMed setid ba74e3cd-b06f-4145-b284-5fd6b84ff3c9). Sections 2, 5.2, 10, 12.3.
  5. Protamine Sulfate Injection, USP, prescribing information, Fresenius Kabi (DailyMed SPL effective 2025-04-29, setid c76876da-b9a8-45d0-9278-7df3288d3a06). Dosage and Administration, Contraindications, Precautions.
  6. Heparin Sodium Injection US prescribing information, Pfizer (DailyMed SPL effective 2025-10-03, setid 56dc3074-f1c5-45a3-b923-f1d14858e06d). Section 10, neutralization of heparin effect.
  7. LOVENOX (enoxaparin) US prescribing information, Sanofi, revised 05/2026 (DailyMed setid 5017a927-2a24-4f27-89f9-27c805bf7d59). Section 10, Overdosage.
  8. ARIXTRA (fondaparinux) US prescribing information, Mylan Institutional, revised 12/2024 (DailyMed setid d3b30c68-cf45-4b46-8ba6-72090f7ba01a). Sections 10, 12.3.
  9. Vitamin K1 (phytonadione injectable emulsion) US prescribing information, Hospira (DailyMed SPL effective 2026-08-09, setid e8808230-2c44-44c6-8cab-8f29b6b34051). Boxed warning, section 2.1.
  10. US Food and Drug Administration. Update on the safety of Andexxa (AstraZeneca): FDA safety communication (page current as of 12/19/2025). US commercial sales ended 22 Dec 2025; FDA considers the risks to outweigh the benefits.
  11. Greenberg SM, Ziai WC, Cordonnier C, et al. 2022 guideline for the management of patients with spontaneous intracerebral hemorrhage: a guideline from the American Heart Association/American Stroke Association. Stroke 2022;53:e282–e361. Sections 5.2.1 (recommendations 1–12, Figure 2) and 5.2.2 (recommendations 1–3). doi:10.1161/STR.0000000000000407
  12. Tomaselli GF, Mahaffey KW, Cuker A, et al. 2020 ACC expert consensus decision pathway on management of bleeding in patients on oral anticoagulants. J Am Coll Cardiol 2020;76:594–622 (Table 1, Figures 2–3, Tables 2 and 4A, sections 5.2–5.6). doi:10.1016/j.jacc.2020.04.053
  13. Gulati D, Dua D, Torbey MT. Hemostasis in intracranial hemorrhage. Front Neurol 2017;8:80 (PMC5351795) — secondary reprint of the NCS/SCCM 2016 tables; its VKA rec 4 prints “>1.4” where the original reads “≥1.4”, and its numbering differs. doi:10.3389/fneur.2017.00080
  14. Frontera JA, Lewin JJ, Rabinstein AA, et al. Guideline for reversal of antithrombotics in intracranial hemorrhage: a statement from the Neurocritical Care Society and Society of Critical Care Medicine. Neurocrit Care 2016;24:6–46 — primary source; the tool uses its original numbering (VKA recs 3–6, FXa rec 5, DTI recs 5, 6 and 9, heparin, LMWH, pentasaccharide, thrombolytic and antiplatelet recommendations). doi:10.1007/s12028-015-0222-x
  15. Guideline Central. Reversal of antithrombotics in intracranial hemorrhage (summary of the NCS/SCCM 2016 guideline), guidelinecentral.com/guideline/41531 — secondary source, consulted for the LMWH wording.
  16. Vallejo MC, Kennedy LS, Dengler B, et al. Treatment of antithrombotic-associated intracranial hemorrhage in adults: a focused guideline update from the Neurocritical Care Society and the Society of Critical Care Medicine. Neurocrit Care 2026 (published 24 Sep 2026; abstract recommendations only — full text not accessible). doi:10.1007/s12028-026-02601-4
  17. Abraham NS, Barkun AN, Sauer BG, et al. ACG-CAG clinical practice guideline: management of anticoagulants and antiplatelets during acute gastrointestinal bleeding and the periendoscopic period. Am J Gastroenterol 2022;117:542–58 (recommendations 1–8; rec 7 text on selective PCC within 24 h). doi:10.14309/ajg.0000000000001627
  18. Sengupta N, Feuerstein JD, Jairath V, et al. Management of patients with acute lower gastrointestinal bleeding: an updated ACG guideline. Am J Gastroenterol 2023;118:208–31 (recommendations 3 and 4; text: “no definitive role for PCC in reversal of factor Xa inhibitors”).
  19. Baharoglu MI, Cordonnier C, Al-Shahi Salman R, et al. Platelet transfusion versus standard care after acute stroke due to spontaneous cerebral haemorrhage associated with antiplatelet therapy (PATCH). Lancet 2016;387:2605–13. doi:10.1016/S0140-6736(16)30392-0
  20. NOVOSEVEN RT (coagulation factor VIIa, recombinant) US prescribing information, Novo Nordisk, revised 07/2020 (DailyMed SPL version 21, published 2022-11-15, setid ea65c32f-8518-4383-b621-17056c0eebc0). Boxed warning (thrombosis), sections 4, 5.1, 5.2.
  21. FEIBA (anti-inhibitor coagulant complex) US prescribing information, Takeda (DailyMed SPL effective 2025-11-27, setid 752604e5-4ea2-44f4-83ed-1569373f6412). Boxed warning (embolic and thrombotic events); section 4 (contraindications: hypersensitivity, DIC, acute thrombosis or embolism); section 11 (contains no heparin).
  22. ARGATROBAN injection US prescribing information, Sagent (DailyMed SPL effective 2026-07-29, setid 629aee90-3bf3-4947-a978-21cbba2e1c41). Sections 2, 10, 12.3.
  23. BIVALIRUDIN for injection US prescribing information, Sandoz (DailyMed SPL effective 2019-09-30, setid ce56f806-7845-429d-a1ce-c2dbf79b22eb). Sections 10, 12.3.
  24. Kumbhani DJ, Armbruster AL, Cheng RK, et al. Direct oral anticoagulants in primary and secondary prevention of thrombotic events: 2026 ACC scientific statement. J Am Coll Cardiol 2026;88:1255–83. doi:10.1016/j.jacc.2026.05.033 — not reviewed (full text not accessible); nothing in this tool rests on it.

Educational reference only — not a substitute for clinical judgment, institutional protocols, or specialist advice. Calculations run in your browser; nothing you enter is sent or stored.