Overview
Warfarin Reversal
Topic Overview
Summary
Warfarin reversal is required for bleeding, supratherapeutic INR, or urgent surgery. The approach depends on INR level, bleeding severity, and urgency of reversal. Options include withholding warfarin, oral or IV vitamin K, prothrombin complex concentrate (PCC — Beriplex/Octaplex), and fresh frozen plasma (FFP). Life-threatening bleeding requires immediate IV vitamin K plus PCC. Minor bleeding or elevated INR without bleeding may only need dose adjustment and vitamin K.
Key Facts
- Minor elevation (INR 5-8): Withhold warfarin ± oral vitamin K
- Major elevation (INR over 8): Withhold + oral/IV vitamin K
- Minor bleeding: Withhold + IV vitamin K ± PCC
- Major/life-threatening bleeding: IV vitamin K + PCC (or FFP if unavailable)
- Urgent surgery: IV vitamin K + PCC
Clinical Pearls
PCC works within minutes; vitamin K takes 6-12 hours — use both for major bleeding
After giving vitamin K, warfarin will be ineffective for days — use bridging if needed
Intracranial haemorrhage on warfarin = immediate reversal (PCC + vitamin K)
Why This Matters Clinically
Warfarin is widely used and reversal is common. Knowing when and how to reverse appropriately prevents both bleeding deaths and thrombotic complications from over-reversal.
Visual Summary
Visual assets to be added:
- Warfarin reversal algorithm by INR and bleeding
- PCC dosing table
- Vitamin K routes and timing
- Decision flowchart
Epidemiology
Incidence
- Warfarin is widely prescribed (AF, VTE, mechanical valves)
- Major bleeding: 1-3% per year
- Intracranial haemorrhage: 0.5% per year
Risk Factors for Bleeding
| Factor | Notes |
|---|---|
| INR over 4 | Significantly increased risk |
| Age over 75 | |
| Previous bleeding | |
| Renal impairment | |
| Liver disease | |
| Concomitant antiplatelet | |
| Drug interactions |
Pathophysiology
Warfarin Mechanism
- Vitamin K antagonist
- Inhibits vitamin K epoxide reductase
- Reduces synthesis of factors II, VII, IX, X (and protein C, S)
Reversal Agents
| Agent | Mechanism | Onset |
|---|---|---|
| Vitamin K (phytomenadione) | Restores factor synthesis | 6-12 hours |
| PCC (4-factor) | Provides factors II, VII, IX, X | Minutes |
| FFP | Contains all clotting factors | 30-60 minutes |
Why PCC is Preferred Over FFP
- Faster onset
- Smaller volume (avoids fluid overload)
- More reliable INR correction
- Lower infection risk
Clinical Presentation
Elevated INR Without Bleeding
Minor Bleeding
Major/Life-Threatening Bleeding
Red Flags
| Finding | Significance |
|---|---|
| Intracranial haemorrhage | Immediate reversal |
| Haemodynamic instability | Major bleeding |
| GCS reduction | Intracranial bleeding |
| INR over 8 | High bleeding risk |
Often asymptomatic
Common presentation.
Detected on routine monitoring
Common presentation.
May have minor bruising
Common presentation.
Clinical Examination
General
- Bruising
- Pallor
- Signs of shock
Site-Specific
- Look for bleeding source
- Neurological examination (if ICH suspected)
- Abdominal examination (retroperitoneal)
Investigations
Blood Tests
| Test | Purpose |
|---|---|
| INR | Assess anticoagulation level |
| FBC | Hb, platelets |
| U&E, LFTs | Baseline; liver affects warfarin |
| Group & Save/Crossmatch | If transfusion needed |
Imaging
- CT head: If intracranial bleed suspected
- CT abdomen: If retroperitoneal bleed suspected
Classification & Staging
By INR Level
| INR | Category |
|---|---|
| 3.0-5.0 | Mildly elevated |
| 5.0-8.0 | Moderately elevated |
| Over 8.0 | Severely elevated |
By Bleeding Severity
| Severity | Features |
|---|---|
| No bleeding | INR elevated, no symptoms |
| Minor bleeding | Epistaxis, bruising, controlled |
| Major bleeding | Hb drop over 2, transfusion needed, critical site |
| Life-threatening | ICH, haemodynamic instability |
Management
No Bleeding, INR Elevated
| INR | Action |
|---|---|
| 5.0-8.0 | Withhold 1-2 doses; reduce maintenance dose |
| Over 8.0 | Withhold + oral vitamin K 1-5 mg |
Minor Bleeding
| Action | Details |
|---|---|
| Withhold warfarin | |
| IV vitamin K | 5 mg slow IV |
| Treat bleeding source | |
| Recheck INR | In 6-12 hours |
Major/Life-Threatening Bleeding
| Action | Details |
|---|---|
| Stop warfarin | |
| IV vitamin K | 5-10 mg slow IV |
| PCC (Beriplex/Octaplex) | 25-50 units/kg (see table below) |
| Transfuse | If needed |
| Treat source | Surgery/endoscopy as needed |
| Recheck INR | 15-30 min post-PCC |
PCC Dosing (4-Factor)
| INR | Dose (units/kg) |
|---|---|
| 2.0-4.0 | 25 |
| 4.0-6.0 | 35 |
| Over 6.0 | 50 |
Maximum 3000-5000 units total
If PCC Unavailable
- FFP 15-30 mL/kg
- Less effective, more volume
Urgent Surgery (Non-Bleeding)
| Urgency | Action |
|---|---|
| Elective (can wait 5 days) | Stop warfarin; let INR normalise |
| Urgent (24-48h) | IV vitamin K ± low-dose PCC |
| Emergency (immediate) | IV vitamin K + full PCC |
After Reversal
- Document indication for warfarin
- Restart anticoagulation when safe (usually 24-72 hours)
- May need bridging with LMWH if high VTE risk
Complications
Of Bleeding
- Death
- Permanent disability (ICH)
- Transfusion reactions
Of Reversal
- Thrombosis (over-reversal in high-risk patients)
- Valve thrombosis (mechanical valves)
- Warfarin resistance after high-dose vitamin K
Prognosis & Outcomes
Prognosis
- Minor bleeding: Excellent
- ICH on warfarin: Mortality 30-50%
Key Factors
- Time to reversal
- Severity of bleeding
- Location of bleeding
Evidence & Guidelines
Key Guidelines
- BSH Guidelines on Oral Anticoagulant Reversal
- NICE NG158: VTE
Key Evidence
- PCC is superior to FFP for warfarin reversal
- 4-factor PCC preferred over 3-factor
Patient & Family Information
What is Warfarin Reversal?
Warfarin is a blood-thinning medication. Sometimes the effect is too strong, or you may need to reverse it for surgery or bleeding.
Why Might I Need Reversal?
- Bleeding that doesn't stop
- Blood test (INR) too high
- Need for urgent surgery
Treatment
- Stopping warfarin
- Vitamin K injection
- A medicine called PCC (blood clotting factors)
What Happens After?
- Your blood thinning level will be monitored
- Warfarin may be restarted when safe
Resources
References
Primary Guidelines
- Keeling D, et al. Guidelines on oral anticoagulation with warfarin - fourth edition. Br J Haematol. 2011;154(3):311-324. PMID: 21671894
Key Reviews
- Sarode R, et al. Efficacy and safety of a 4-factor prothrombin complex concentrate in patients on vitamin K antagonists presenting with major bleeding. Circulation. 2013;128(11):1234-1243. PMID: 23935011
Guidelines
- NICE. Venous Thromboembolic Diseases (NG158). 2020.