Overview
DOAC Bleeding
Quick Reference
Critical Alerts
- Life-threatening bleeding requires immediate reversal plus supportive care
- Idarucizumab (Praxbind) reverses dabigatran specifically
- Andexanet alfa (Andexxa) reverses factor Xa inhibitors (rivaroxaban, apixaban)
- 4-factor PCC (Kcentra) is alternative if specific antidote unavailable
- Hemodialysis removes dabigatran but not factor Xa inhibitors
Key Diagnostics
- CBC (hemoglobin, platelet count)
- Coagulation studies (PT, aPTT, fibrinogen)
- Specific drug levels if available (anti-Xa activity for factor Xa inhibitors)
- Type and crossmatch
- Thrombin time (sensitive to dabigatran)
- Renal function (affects drug clearance)
Emergency Treatments
- Dabigatran: Idarucizumab 5g IV (two 2.5g doses)
- Factor Xa inhibitors: Andexanet alfa OR 4-factor PCC 50 units/kg
- Supportive care: Transfuse pRBCs, FFP, platelets as needed
- Local hemostatic measures: Direct pressure, topical agents
- Hold anticoagulant: Determine when to resume
Definition
Direct oral anticoagulants (DOACs) are a class of anticoagulants that directly inhibit specific coagulation factors, either thrombin (factor IIa) or factor Xa. Bleeding complications are the major adverse effect, and management differs from warfarin-related bleeding.
DOAC Classification
| Mechanism | Drug | Trade Name | Half-Life |
|---|---|---|---|
| Direct thrombin inhibitor | Dabigatran | Pradaxa | 12-17 hours |
| Factor Xa inhibitors | Rivaroxaban | Xarelto | 5-13 hours |
| Apixaban | Eliquis | 8-15 hours | |
| Edoxaban | Savaysa | 10-14 hours | |
| Betrixaban | Bevyxxa | 19-27 hours |
Indications for DOACs
- Atrial fibrillation (stroke prevention)
- VTE treatment and prophylaxis
- Post-orthopedic surgery prophylaxis
- Secondary prevention after acute coronary syndrome (rivaroxaban)
Bleeding Risk Factors
| Factor | Mechanism |
|---|---|
| Advanced age | Altered pharmacokinetics |
| Renal impairment | Reduced clearance (especially dabigatran) |
| Low body weight | Higher drug levels |
| Drug interactions | CYP3A4/P-gp inhibitors |
| Concurrent antiplatelet therapy | Additive bleeding risk |
| Prior bleeding history | Increased recurrence |
| Recent surgery/trauma | Surgical bleeding sites |
Pathophysiology
Mechanism of DOACs
Dabigatran (Direct Thrombin Inhibitor)
- Binds directly to active site of thrombin
- Prevents conversion of fibrinogen to fibrin
- Reversible, competitive inhibition
- Primarily renally cleared (80%)
Factor Xa Inhibitors
- Bind directly to active site of factor Xa
- Block conversion of prothrombin to thrombin
- Affect both free and clot-bound factor Xa
- Variable renal/hepatic clearance
Reversal Agent Mechanisms
Idarucizumab
- Humanized monoclonal antibody fragment
- Binds dabigatran with very high affinity (350x thrombin)
- Immediately neutralizes dabigatran
Andexanet Alfa
- Modified recombinant factor Xa (inactive)
- Binds and sequesters factor Xa inhibitors
- Also binds LMWH, fondaparinux
- Short duration - requires infusion
Prothrombin Complex Concentrate (PCC)
- Contains factors II, VII, IX, X
- Bypasses factor Xa inhibition
- Non-specific reversal
- Thrombotic risk
Time Course of Effect
| Drug | Peak Effect | Duration |
|---|---|---|
| Dabigatran | 0.5-2 hours | 12-17 hours |
| Rivaroxaban | 2-4 hours | 5-13 hours |
| Apixaban | 1-3 hours | 8-15 hours |
Clinical Implication: If last dose was >24-48 hours ago, drug effect likely minimal
Clinical Presentation
Types of Bleeding
Life-Threatening
Major (Non-Life-Threatening)
Minor
Assessment of Bleeding Severity
| Severity | Features |
|---|---|
| Life-threatening | Hemodynamic instability, critical location (ICH, spinal), need for emergent intervention |
| Major | >g/dL hemoglobin drop, transfusion required, critically-located but stable |
| Minor | No hemodynamic effect, no transfusion needed |
Signs of Severe Bleeding
Intracranial hemorrhage
Common presentation.
Spinal/epidural hematoma
Common presentation.
Pericardial tamponade
Common presentation.
Retroperitoneal hemorrhage
Common presentation.
Massive GI bleeding with hemodynamic instability
Common presentation.
Airway compromise (neck hematoma)
Common presentation.
Red Flags (Life-Threatening)
Critical Presentations
| Red Flag | Concern | Action |
|---|---|---|
| Altered mental status + anticoagulation | ICH | STAT CT head, reversal |
| Signs of shock | Massive hemorrhage | Resuscitation, reversal, transfusion |
| New focal neurological deficit | ICH or spinal hematoma | Emergent imaging, reversal |
| Rapidly expanding neck hematoma | Airway compromise | Secure airway, reversal |
| Pericardial friction rub + hypotension | Hemorrhagic tamponade | Echo, pericardiocentesis |
| Rigid abdomen + hypotension | Intra-abdominal hemorrhage | Surgical consultation, reversal |
Intracranial Hemorrhage
Highest Priority for Reversal
- Mortality 30-50% even with treatment
- Early hematoma expansion worsens outcome
- Time-critical reversal indicated
- Neurosurgical consultation
Differential Diagnosis
Other Causes of Bleeding in Anticoagulated Patients
| Condition | Key Features |
|---|---|
| Underlying structural lesion | GI: malignancy, AVM, peptic ulcer |
| Coagulopathy (non-DOAC) | Liver disease, DIC, vitamin K deficiency |
| Thrombocytopenia | Low platelet count |
| Drug-drug interaction | Enhanced anticoagulant effect |
| Overdose (intentional) | History, very high level if available |
| Coincidental bleeding | Trauma, separate pathology |
GI Bleeding Differential
- Peptic ulcer
- Gastric/esophageal varices
- Malignancy
- Diverticular bleeding
- AVM/angiodysplasia
- Inflammatory bowel disease
Diagnostic Approach
Initial Assessment
Key History
- Which DOAC? (determines reversal strategy)
- Time of last dose?
- Indication for anticoagulation
- Bleeding source and duration
- Other medications (antiplatelets, NSAIDs)
- Renal function
Laboratory Studies
| Test | Purpose | Interpretation |
|---|---|---|
| CBC | Hemoglobin, platelets | Quantify blood loss |
| PT/INR | Coagulation screening | May be prolonged with rivaroxaban |
| aPTT | Coagulation screening | May be prolonged with dabigatran |
| Thrombin time (TT) | Dabigatran presence | Very sensitive; if normal, no dabigatran |
| Dilute thrombin time (dTT) | Dabigatran level | Quantitative |
| Anti-Xa activity | FXa inhibitor level | Quantitative; send with drug specified |
| Fibrinogen | Coagulation | |
| Type & Screen | Transfusion preparation | |
| BMP | Renal function | Affects clearance |
Imaging
- CT head: If any concern for ICH
- CT abdomen/pelvis: Retroperitoneal bleeding, intra-abdominal source
- Neck CT/direct visualization: Expanding neck hematoma
- Endoscopy/colonoscopy: GI bleeding source when stable
Timing Considerations
| Last Dose | Implication |
|---|---|
| <2 hours ago | Absorption may be ongoing; consider activated charcoal |
| 2-12 hours | Likely therapeutic effect present |
| 12-24 hours | Drug level declining |
| >4-48 hours | Effect likely minimal unless renal impairment |
Treatment
Supportive Care (All Patients)
1. ABCs - secure airway if needed
2. Large-bore IV access (two 18G or larger)
3. Type and crossmatch
4. Transfuse pRBCs for Hb <7 g/dL (higher threshold if ongoing bleeding)
5. Direct pressure to bleeding sites
6. Hold anticoagulant
Specific Reversal Agents
Dabigatran: Idarucizumab (Praxbind)
Dose: 5g IV (two 2.5g vials)
Administration: Sequential IV boluses or infusion over 5-10 min
Onset: Immediate
Duration: 24 hours
Repeat dosing: Consider if bleeding recurs (rare)
Notes:
- Specific for dabigatran only
- No rebound anticoagulation
- Very expensive but effective
Factor Xa Inhibitors: Andexanet Alfa (Andexxa)
Dosing based on drug and timing:
Low dose: 400mg bolus, then 4mg/min x 2 hours
- Apixaban ≤5mg >8h before OR
- Rivaroxaban ≤10mg >8h before
High dose: 800mg bolus, then 8mg/min x 2 hours
- Apixaban >5mg or <8h before
- Rivaroxaban >10mg or <8h before
- Edoxaban (any dose/time)
- Enoxaparin
Notes:
- Very expensive
- Short duration - requires infusion
- Thrombotic risk (~10% at 30 days)
- Effect wanes after infusion stops
4-Factor PCC (Kcentra) - Alternative
Dose: 50 units/kg IV (max 5000 units)
Use when:
- Andexanet alfa not available
- Life-threatening bleeding requiring reversal
- Cost consideration
Notes:
- Non-specific reversal
- Contains factors II, VII, IX, X
- Thrombotic risk
- Off-label for DOAC reversal
Activated Charcoal
- Consider if ingestion within 2 hours
- May reduce absorption
- Dose: 50g PO (if airway protected)
Hemodialysis
- Dabigatran: Can be dialyzed (35-60% removed in 4 hours)
- Factor Xa inhibitors: NOT effectively dialyzed (highly protein bound)
Transfusion Targets
| Product | Indication | Target |
|---|---|---|
| pRBCs | Anemia | Hb >-8 g/dL (higher if ongoing bleeding) |
| Platelets | Severe thrombocytopenia with bleeding | >0,000/μL |
| FFP | Coagulopathy, massive transfusion | PT correction |
| Cryoprecipitate | Fibrinogen <150 mg/dL | Fibrinogen >00 |
Bleeding Site-Specific Management
| Site | Management |
|---|---|
| GI bleeding | Endoscopy, octreotide if variceal, TXA consider |
| ICH | Reversal, BP control (target <140 systolic), consider surgery |
| Airway hematoma | Secure airway early |
| Retroperitoneal | IR embolization vs surgery |
| Muscle/joint | Compression, consider IR drainage if large |
Disposition
ICU Admission Criteria
- Life-threatening bleeding
- ICH
- Hemodynamic instability
- Post-reversal monitoring
- Need for ongoing resuscitation
Floor/Monitored Bed
- Major bleeding, now controlled
- Need for serial hemoglobin monitoring
- Moderate transfusion requirement
- Need to determine anticoagulation plan
Observation
- Minor bleeding
- DOAC held, stable
- Clear source identified and controlled
Discharge (Rare in Significant DOAC Bleeding)
- Minor bleeding resolved
- Clear follow-up plan
- Decision made regarding anticoagulation
Resuming Anticoagulation
| Scenario | Timing |
|---|---|
| Minor bleeding | May resume after source controlled |
| Major GI bleeding | 7-14 days, depending on source |
| ICH | Varies; often weeks to never; multidisciplinary decision |
| Surgical bleeding | When surgical team approves |
Consider:
- Indication strength for anticoagulation
- Bleeding recurrence risk
- Whether alternative anticoagulation or lower dose
Patient Education
Understanding DOAC Bleeding
- DOACs are blood thinners that prevent clots
- They can increase bleeding risk
- Most bleeding is minor, but severe bleeding can occur
- Know the signs of serious bleeding
When to Seek Emergency Care
- Any head injury (even minor)
- Signs of internal bleeding: vomiting blood, black stools, blood in urine
- Uncontrolled bleeding
- Dizziness, weakness, or confusion
- Severe headache
- Swelling or pain in abdomen
Prevention
- Take medication as prescribed
- Avoid NSAIDs (ibuprofen, naproxen)
- Inform all healthcare providers
- Wear medical alert identification
- Be cautious with activities that could cause injury
Special Populations
Renal Impairment
- Dabigatran most affected (80% renal clearance)
- Adjust doses per package insert
- Prolonged drug effect in renal failure
- Hemodialysis removes dabigatran
Elderly
- Higher bleeding risk
- More likely to have renal impairment
- Falls risk increases ICH risk
- May need dose adjustment
Obesity
- Standard dosing generally applies
- Limited data on extremes of weight
- Consider drug levels if available
Trauma
- Determine time since last dose
- Low threshold for reversal in severe trauma
- Balance bleeding risk vs thrombotic risk
Perioperative Bleeding
- Timing of last dose critical
- Reversal if emergent surgery and recent dose
- Surgical hemostasis important
Quality Metrics
Performance Indicators
| Metric | Target |
|---|---|
| DOAC identified and documented | 100% |
| Time to reversal agent (life-threatening) | <60 min |
| Type and screen ordered | 100% |
| Renal function checked | 100% |
| Hematology/toxicology consultation (severe) | As needed |
| Neuroimaging for altered mental status | <30 min |
Documentation Requirements
- Specific DOAC and dose
- Time of last dose
- Bleeding site and severity
- Laboratory values
- Reversal agent used and timing
- Blood products given
- Response to treatment
- Plan for resuming anticoagulation
Key Clinical Pearls
Diagnostic Pearls
- Know which DOAC - determines reversal strategy
- Time since last dose matters - >48 hours, drug effect minimal
- Thrombin time screens for dabigatran - if normal, no dabigatran effect
- Anti-Xa activity for factor Xa inhibitors - need to specify drug
- Renal function affects clearance - especially dabigatran
Treatment Pearls
- Idarucizumab for dabigatran - specific, immediate, complete reversal
- Andexanet or PCC for factor Xa inhibitors - andexanet preferred if available
- Dialysis removes dabigatran but not factor Xa inhibitors
- PCC is reasonable alternative if specific antidote unavailable
- Supportive care remains essential - transfusion, pressure, source control
Disposition Pearls
- ICU for life-threatening bleeding - close monitoring needed
- Hematology input valuable for complex cases
- Anticoagulation resumption is case-by-case decision
- Document decision-making about anticoagulation plan
- Close follow-up essential for any significant bleed
References
- Tomaselli GF, et al. 2020 ACC Expert Consensus Decision Pathway on Management of Bleeding in Patients on Oral Anticoagulants. J Am Coll Cardiol. 2020;76(5):594-622.
- Pollack CV, et al. Idarucizumab for Dabigatran Reversal — Full Cohort Analysis (RE-VERSE AD). N Engl J Med. 2017;377(5):431-441.
- Connolly SJ, et al. Andexanet Alfa for Acute Major Bleeding Associated with Factor Xa Inhibitors (ANNEXA-4). N Engl J Med. 2016;375(12):1131-1141.
- Cuker A, et al. Reversal of direct oral anticoagulants: Guidance from the Anticoagulation Forum. Am J Hematol. 2019;94(6):697-709.
- Levy JH, et al. Anticoagulation: Current and future state. Anesthesiology. 2021;134(2):340-351.
- Frontera JA, et al. Guideline for Reversal of Antithrombotics in Intracranial Hemorrhage. Neurocrit Care. 2016;24(1):6-46.
Version History
| Version | Date | Changes |
|---|---|---|
| 1.0 | 2025-01-15 | Initial comprehensive version with 14-section template |