Reversal is a trade: you are buying hemostasis with thrombosis risk. Reverse for life-threatening or critical-site bleeding (intracranial, airway, pericardial, compartment) or an emergent procedure, not for a number. Every case: stop the drug, note the time of the last dose, check renal function, and give the reversal agent at a full dose the first time. Andexanet alfa (Andexxa) was withdrawn from the US market effective December 22, 2025, so 4-factor PCC is the practical option for factor Xa inhibitor bleeding. Adult dosing throughout; confirm against your institutional protocol.
No platelets for spontaneous ICH without surgery (PATCH)
Desmopressin 0.3-0.4 mcg/kg IV once (label max 20 mcg)
Platelets only if going to emergency neurosurgery.
Underlined entries jump to the detail below. Kcentra is FDA-labeled only for VKA reversal, so every PCC use for a DOAC, fondaparinux, or a DTI is off-label. Pediatric dosing is outside the scope of this card.
Not on the label. NCS/SCCM 2016 suggests the lowest marketed dose (25 units/kg); AHA/ASA 2022 calls PCC at INR 1.3-1.9 “may be reasonable” (2b).
Judgment call
Kcentra and Balfaxar labeling: dose on actual weight up to 100 kg and never exceed the maximum. Worked example (label): 80 kg, INR 5.0 → 35 × 80 = 2800 units. Infuse Kcentra at 0.12 mL/kg/min (about 3 units/kg/min), max 8.4 mL/min. Balfaxar is labeled for urgent surgery or invasive procedures; Kcentra for both major bleeding and procedures.
Step
What to do
Vitamin K
10 mg IV (NCS/SCCM 2016; ACC 2020 allows 5-10 mg IV for major bleeding), given with the PCC, never instead of it. Infuse no faster than 1 mg/min (boxed warning: fatal anaphylaxis with IV). Effect starts in 1-2 h; full INR correction can take 12-24 h.
Fixed-dose option
ACC 2020 permits 1000 units for non-intracranial major bleeding and 1500 units for ICH. No society guideline prefers fixed dosing; NCS/SCCM 2016 and AHA/ASA 2022 remain INR- and weight-based. If you use it, build in the recheck and escalation dose.
Recheck
INR 15-60 min after PCC, then every 6-8 h for 24-48 h (NCS/SCCM 2016). ICH target INR <1.4.
Plasma
10-15 mL/kg only when PCC is unavailable or contraindicated. AHA/ASA 2022: 4F-PCC is recommended over FFP (Class 1). Plasma is slow to thaw and the volume is a problem in heart failure.
Repeat PCC
Kcentra and Balfaxar labels: repeat dosing is not recommended (safety and efficacy not established). Many institutional fixed-dose protocols still include one predefined supplemental dose; know which one yours uses.
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In fixed-dose cohorts, failure tracked with the starting INR more than with body weight. If your protocol uses a flat dose, the escalation trigger should be driven by the post-dose INR. See the Practice Signal on fixed vs weight-based 4F-PCC dosing below for the trial-level detail.
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Kcentra contains heparin and is contraindicated in known heparin-induced thrombocytopenia and in DIC. Actual potency per vial varies (a “1000 unit” vial holds 800-1240 units), so order in units of factor IX and let pharmacy round to vials.
Factor Xa Inhibitors: Apixaban, Rivaroxaban, Edoxaban ↑ back to index
Option
Dose and source
4F-PCC, fixed
2000 units IV (Anticoagulation Forum 2019). Fast to prepare, no weight needed.
4F-PCC, weight-based
25-50 units/kg IV in published cohorts; ACC 2020 and NCS/SCCM 2016 specify 50 units/kg. In ANNEXA-I usual care, the median PCC dose was 3000 units.
Activated charcoal
50 g if the last dose was within 2 h and the airway is protected or aspiration risk is low (NCS/SCCM 2016).
Andexanet alfa
Not available in the US since December 22, 2025. ANNEXA-I (NEJM 2024, ICH): better hemostatic efficacy (67.0% vs 53.1%) but more thrombotic events (10.3% vs 5.6%), including ischemic stroke 6.5% vs 1.5%, with no difference in 30-day death. Still marketed outside the US as Ondexxya.
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The guidelines still name andexanet. ACC 2020, NCS/SCCM 2016, and AHA/ASA 2022 (andexanet 2a; 4F-PCC or aPCC 2b for ICH) were all written while it was on the market, so your order set may still point to it. PCC for factor Xa inhibitor bleeding rests on cohort data, not randomized trials against placebo.
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Drug on board? NCS/SCCM 2016 suggests reversal when the bleed occurs within 3-5 half-lives of the last dose, or at any time in liver failure. If the timing is unknown, assume the drug is on board.
5 g IV as two 2.5 g/50 mL vials, consecutive infusions or back-to-back bolus. Reversal is immediate on aPTT, dTT, and ECT.
Second dose
Another 5 g may be considered if bleeding recurs with elevated coagulation tests, or for a second urgent procedure with elevated coagulation tests (label; repeat-dose safety not established).
No idarucizumab
aPCC or 4F-PCC 50 units/kg IV (ACC 2020; NCS/SCCM 2016). Hemodialysis if renal insufficiency or overdose (NCS/SCCM 2016). Charcoal 50 g if within 2 h.
Restart
Dabigatran can be restarted 24 h after idarucizumab if hemostasis is secure (label).
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Rebound. In a minority of patients aPTT and ECT rise again 12-24 h after the dose as dabigatran redistributes from tissue. Recheck coagulation tests, especially with a low CrCl.
1 mg protamine per 100 units of heparin received in the prior 2-3 h. Max 50 mg per dose, no faster than 5 mg/min. If aPTT stays high, 0.5 mg per 100 units (NCS/SCCM 2016).
Enoxaparin
1 mg per 1 mg enoxaparin if ≤8 h; 0.5 mg per 1 mg at 8-12 h; often not useful beyond 12 h. Max 50 mg per dose.
Fondaparinux
Protamine does not bind it. Off-label aPCC 20 units/kg; rFVIIa 90 mcg/kg if aPCC is contraindicated or unavailable. Low-quality evidence.
Time-decay table for UFH boluses, dalteparin dosing, rebound monitoring, and the allergy risk factors are on the Antidotes card. Do not round protamine up: excess protamine is itself an anticoagulant.
Stop the infusion and support. NCS/SCCM 2016 lists aPCC or 4F-PCC 50 units/kg as an option and recommends against FFP or rFVIIa for DTI-related ICH.
Bivalirudin
25 min; renal (lasts longer when CrCl is low)
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Many of these patients have HIT. Stopping the DTI leaves an active prothrombotic state with no anticoagulant, so plan the restart (or alternative) at the same time as the hold. And remember Kcentra contains heparin.
Stop the alteplase infusion. STAT CT, CBC, PT/INR, aPTT, fibrinogen, type and cross.
2
Cryoprecipitate 10 units IV empirically, then redose to keep fibrinogen ≥150 mg/dL (NCS/SCCM 2016; AHA/ASA 2017 statement). The AHA/ASA 2018/2019 stroke guideline table and ENLS redose for fibrinogen <200 mg/dL; know which threshold your protocol uses.
3
Antifibrinolytic, as an adjunct or when cryoprecipitate cannot be given: tranexamic acid 1000 mg IV over 10 min (AHA/ASA stroke guideline table; ENLS) or 10-15 mg/kg IV over 20 min (NCS/SCCM 2016), oraminocaproic acid 4-5 g IV over 1 h, then 1 g/h until bleeding is controlled (many protocols cap the infusion at 8 h).
4
Some protocols add platelets if the count is <100,000 (minimal evidence). Call neurosurgery and hematology early.
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Tenecteplase (0.25 mg/kg, max 25 mg, per the 2026 AHA/ASA stroke guideline) has no separate reversal data. The same cryoprecipitate-plus-antifibrinolytic approach is used by extrapolation. All of this rests on expert opinion and case series, not trials.
Do not transfuse platelets. PATCH (Lancet 2016, n=190, mostly aspirin): death or dependence at 3 months was higher with platelets (adjusted OR 2.05, 95% CI 1.18-3.56). AHA/ASA 2022: potentially harmful (Class 3: Harm).
ICH going to emergency neurosurgery on aspirin
Platelet transfusion may be considered to reduce postoperative bleeding (AHA/ASA 2022, 2b).
Desmopressin
0.3 mcg/kg IV in 50 mL NS over 15-30 min (labeled hemostatic dose; the current label caps each dose at 20 mcg, which is reached at about 67 kg). NCS/SCCM 2016 suggested 0.4 mcg/kg once. AHA/ASA 2022: benefit uncertain (2b). Restrict free water and check sodium; tachyphylaxis if redosed within 48 h.
Ticagrelor
Platelet transfusion is less effective against ticagrelor; some institutional protocols give more than 2 units. Bentracimab (REVERSE-IT, single-arm) reverses it within minutes, but we could not confirm FDA approval as of Oct 2026. Check Drugs@FDA before you plan around it.
Thrombosis After Reversal, and When to Restart
Question
Answer
How real is the clot risk?
Kcentra registration trials: thromboembolic events 6.8% with PCC vs 7.1% with plasma (pooled). ANNEXA-I: 10.3% with andexanet vs 5.6% with usual care. PROCOAG (JAMA 2023, non-anticoagulated trauma): 4F-PCC gave no transfusion benefit and more thromboembolism (35% vs 24%).
Low thrombotic risk
ACC 2020: consider stopping anticoagulation (for example AF with low CHA2DS2-VASc, or provoked VTE more than 3 months ago).
Critical-site bleed or unknown source
ACC 2020: delay the restart. After ICH, about 4 weeks is the usual starting point; this is a shared decision with neurology or neurosurgery.
GI bleed
Restarting at 7 days or later was associated with better survival and less thromboembolism (cohort data summarized in ACC 2020).
Everyone else
Restart as soon as hemostasis is secure (ACC 2020).
Platelets for spontaneous ICH on an antiplatelet. PATCH showed harm, and AHA/ASA 2022 calls it Class 3: Harm unless the patient is going to emergency surgery. This is still ordered reflexively. Ask before you release the unit.
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PCC without vitamin K for warfarin. The factors from PCC decline over hours; without vitamin K the INR drifts back up and the bleed restarts. Both labels say to give vitamin K concurrently.
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PCC as a general “make it clot” drug. In PROCOAG, 4F-PCC in trauma patients who were not anticoagulated did not reduce blood product use and increased thromboembolic events. Use it to replace factors that a drug has removed.
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Kcentra in a patient with HIT. Each vial contains heparin and the label lists known HIT as a contraindication. This is most likely in a patient on argatroban or bivalirudin.
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Pushing IV vitamin K, or rounding protamine up. Vitamin K IV: no faster than 1 mg/min. Protamine: max 50 mg, no faster than 5 mg/min, and excess protamine causes bleeding.