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Anesthesiology APPLIED Exam › Critical care, resuscitation and trauma

Anticoagulant reversal and inherited bleeding disorders

Critical care, resuscitation and trauma·~5 min read· Physician-reviewed✓ Sourced · 10

Stem

A 79-year-old woman, 70 kg, on apixaban 5 mg twice daily for atrial fibrillation, fell down her stairs. Her last dose was 3 hours ago. CT shows a shattered spleen with free fluid. Blood pressure is 84/50 after 2 units of red cells, heart rate 118. Creatinine 0.9 mg/dL, hemoglobin 8.1 g/dL, platelets 190,000, INR 1.3. The surgeon is taking her for an emergency splenectomy now.

Question

How will you manage her anticoagulation?

Ideal answer

HeadlineThis is life-threatening bleeding on a factor Xa inhibitor at peak effect, the one setting where I reverse, and I reverse while the surgeon opens.

  1. Stop apixaban and read the clock. Last dose 3 hours ago, normal kidneys: full effect, and a near-normal INR does not tell me otherwise.
  2. 4F-PCC 50 units/kg, about 3500 units, now: andexanet left the US market in December 2025,1 and the ACC pathway names PCC as the alternative.2
  3. Run it as massive hemorrhage: balanced products, calcium, warming, tranexamic acid, with viscoelastic testing steering what comes next.
  4. General anesthesia, rapid sequence, no neuraxial, because high-dose apixaban needs 72 hours before a block.3

Watch for: clot forming in the field, falling product needs; then thrombosis, since PCC and her atrial fibrillation both push the other way.

Breaking down the answer

  • Reverse only for a major bleed — critical site, instability, a 2 g/dL hemoglobin fall or 2 units transfused; nonmajor bleeding gets none.4 Changes if: stable, I stop and wait; ASRA advises against reversing a DOAC just to place a block.3
  • Warfarin — 4F-PCC over plasma,4 dosed by INR: 25, 35 or 50 units/kg (caps 2500, 3500, 5000), with vitamin K, because PCC wears off and is not repeated.5 Vitamin K 5–10 mg IV; plasma 10–15 mL/kg only without PCC.2
  • Dabigatran — idarucizumab 5 g IV; PCC or activated PCC 50 units/kg if it is unavailable.2
  • Heparins — protamine 1 mg per 100 units given minutes ago, 0.5 mg at 30 minutes, 0.25–0.375 mg after 2 hours, at most 50 mg per 10 minutes.6 Enoxaparin within 8 hours: 1 mg per mg, neutralizing only about 60%.6
  • Von Willebrand disease — DDAVP for type 1 and trial-proven 2A, 2M and 2N; VWF concentrate for 2B, 3 and nonresponders.7 Major surgery: VWF and factor VIII activity at least 0.50 IU/mL for 3 days, and no DDAVP.7
  • Measuring and limits — an apixaban-calibrated anti-Xa level confirms residual drug, and ASRA accepts ≤0.1 IU/mL, though it advises against routine anti-Xa monitoring;3 viscoelastic testing then steers products. Fondaparinux has no known antidote, protamine included.8

Follow-up question

Your next patient is a 30-year-old man, 80 kg, with severe hemophilia A and no inhibitor, for an urgent laparoscopic appendectomy. What do you need before you start?

Follow-up answer

HeadlineA factor VIII level, not a coagulation screen; I call his hemophilia center and treat before incision.

I give factor VIII to a peak of 80–100 IU/dL; each unit per kg raises it about 2 IU/dL, so 50 units/kg, 4000 units.9 I check a peak 15–30 minutes later,9 then hold troughs at 60–80 IU/dL for days 1–3 and lower after.9 No intramuscular injections or NSAIDs. If he has an inhibitor, bypassing agents instead: rFVIIa 90 µg/kg.9

Pitfalls that cost points

  • Reversing apixaban to make a hip fracture or a spinal "work" on schedule.
  • Repeating PCC for ongoing ooze instead of measuring fibrinogen and platelets.
  • Trusting the aPTT on emicizumab: it falls into the normal range regardless of protection.9

Rapid-fire

Q: How do you give DDAVP? A: 0.3 µg/kg IV, maximum 20 µg, in saline over 15–30 minutes, 30 minutes before surgery.10

Q: What are its two main risks? A: Hyponatremia with seizures, so fluids stay at maintenance for 24 hours;7 and tachyphylaxis, so no more than once every 24 hours and for no more than 3 days without the hemophilia center.7

Q: How do you dose factor IX for hemophilia B? A: Plasma-derived factor IX raises the level about 1 IU/dL per unit/kg; target 60–80 IU/dL before major surgery.9

Q: Why avoid activated PCC on emicizumab? A: The combination has caused thrombotic microangiopathy and venous thrombosis.9

Q: Why did andexanet leave the market? A: ANNEXA-I showed thrombosis in 14.6% versus 6.9% with usual care; the FDA judged the risks greater than the benefits.1

Numbers to know

Item Value
4F-PCC, warfarin INR 2–<4: 25 U/kg; 4–6: 35 U/kg; >6: 50 U/kg5
PCC, Xa inhibitor or dabigatran without its agent 50 U/kg2
Idarucizumab 5 g IV2
Protamine, heparin 1 mg/100 U; ≤50 mg per 10 min6
DDAVP 0.3 µg/kg, max 20 µg10
VWD major surgery VWF and FVIII ≥0.50 IU/mL for ≥3 days7
Hemophilia major surgery peak FVIII 80–100; FIX 60–80 IU/dL9

Sources

  1. 1.Update on the Safety of Andexxa (AstraZeneca): FDA Safety Communication · US Food and Drug Administration, 2025 · fda.govUS sales ended 22 December 2025; ANNEXA-I thrombosis 14.6% vs 6.9%.
  2. 2.Considerations for Anticoagulation Reversal/Hemostasis (based on the 2020 ACC ECDP) · American College of Cardiology (copy hosted by UConn School of Pharmacy), 2020 · pharmacy.media.uconn.eduDose table: 4F-PCC by INR, fixed-dose option, PCC 50 units/kg for factor Xa inhibitors and dabigatran when the specific agent is unavailable, vitamin K, plasma 10-15 mL/kg.
  3. 3.ASRA Guidelines for Regional Anesthesia with Antithrombotic or Thrombolytic Therapy 5th Edition - Summary of Recommendations · Guideline Central / ASRA Pain Medicine, 2025 · guidelinecentral.com
  4. 4.2020 ACC Expert Consensus Decision Pathway on Management of Bleeding in Patients on Oral Anticoagulants: Key Points · American College of Cardiology, 2020 · acc.org
  5. 5.Kcentra dosage (FDA labeling) · Drugs.com (FDA prescribing information) · drugs.com
  6. 6.Protamine sulfate (AHFS monograph) · Drugs.com / ASHP · drugs.com
  7. 7.MASAC Document 266: MASAC Recommendations Regarding the Treatment of von Willebrand Disease · National Bleeding Disorders Foundation (adapting the 2021 ASH/ISTH/NHF/WFH guideline), 2021 · bleeding.org
  8. 8.ARIXTRA (fondaparinux sodium) injection prescribing information · DailyMed (FDA labeling, Mylan Institutional) · dailymed.nlm.nih.govOverdosage: there is no known antidote for ARIXTRA.
  9. 9.WFH Guidelines for the Management of Hemophilia, 3rd edition · World Federation of Hemophilia, 2020 · www1.wfh.orgSrivastava et al., Haemophilia 2020;26(Suppl 6). Table 7-2 (higher-dose practice pattern used here); chapter 5 dosing; chapter 3 emicizumab and assays.
  10. 10.DDAVP injection dosage (FDA labeling) · Drugs.com (FDA prescribing information) · drugs.com

Facts on this page were checked against these sources on Oct 22, 2026. Guidelines change; confirm doses against current institutional protocols.

Related topics

Neuraxial blocks and anticoagulants (ASRA)Massive hemorrhage and transfusionDisseminated intravascular coagulationCardiopulmonary bypass: conduct and separationAtrial fibrillation: new onset and chronicTrauma: initial management and damage control
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