How should emicizumab prophylaxis be managed for a patient undergoing dental extraction and what measures can be taken to prevent breakthrough bleeding?

Management of Dental Extraction in Patients on Emicizumab Prophylaxis

Pre-Procedure Planning

For most patients on emicizumab prophylaxis undergoing dental extraction, the procedure can be performed safely without additional factor replacement therapy, particularly for low-risk extractions, using local hemostatic measures and tranexamic acid. 1, 2

Risk Stratification

Assess the local bleeding risk based on three key factors 2:

• Method of extraction (simple vs. surgical)
• Number of teeth being extracted (≤3 teeth per visit is standard) 3
• Site of extraction (anterior vs. posterior, proximity to major vessels)

Low Local Bleeding Risk Procedures

For simple extractions of 1-3 teeth 2:

• Continue emicizumab prophylaxis without interruption 2
• No additional factor replacement may be necessary in approximately one-third of cases 2
• Consider tranexamic acid as an adjunct hemostatic agent 1
• Use local hemostatic measures (detailed below) 2

High Local Bleeding Risk Procedures

For surgical extractions, multiple teeth (>3), or complex cases 2:

• Plan for factor replacement therapy or bypassing agents 2
• Recombinant FVIIa (eptacog alfa) is the preferred bypassing agent due to safety profile with emicizumab 1
• Dosing options for rFVIIa: either 90 μg/kg every 3 hours for 3 doses OR single dose of 270 μg/kg 1
• Avoid activated prothrombin complex concentrate (APCC) or use with extreme caution due to boxed warning for thrombotic complications when combined with emicizumab 1, 4

Pre-Operative Assessment

Check current inhibitor status before the procedure 4:

• Bethesda unit level must be determined to guide bypassing agent selection 4
• For patients with low-titer inhibitors (<2 BU), higher doses of FVIII concentrates may be effective as an alternative 1, 4
• This information is critical for the surgical team to avoid contraindicated combinations 4

Consider rotational thromboelastometry (ROTEM) for peri-operative coagulation monitoring to guide factor replacement decisions 2, 5

Intra-Operative Local Hemostatic Measures

Apply the following local measures universally 2:

• Absorbable hemostatic agents (gelatin sponge, oxidized cellulose, or fibrin glue) placed in extraction socket 2, 6
• Suturing of extraction sites 2, 6
• Mouth splint application (used in 84-100% of cases in successful protocols) 2
• Tranexamic acid-soaked gauze for topical hemostasis 1

Post-Operative Management

Immediate Post-Extraction (First 30 Minutes)

• Apply direct compression with gauze for 20-30 minutes 6, 3
• Most mild oozing resolves with mechanical compression alone 6, 3

Factor Replacement Duration (If Used)

For patients receiving bypassing agents 2, 5:

• Continue dosing based on bleeding risk and clinical response
• In one successful protocol: rFVIIa every 3 hours on day 1, every 4 hours on day 2, every 6 hours on day 3, then discontinue on day 4 5
• Adjust based on clinical bleeding and coagulation monitoring 5

Monitoring Period

• First 3 days post-operatively are highest risk for bleeding episodes 6
• Most bleeding events (91.67%) are mild and controlled with local measures 6
• Instruct patients to report persistent oozing or marked hemorrhage beyond 20 minutes despite compression 6

Management of Breakthrough Bleeding

If bleeding occurs despite initial measures 6:

1. First-line: Mechanical compression with gauze for 20 minutes
2. Second-line: Revision of wound, application of fibrin glue, and resuturing
3. Third-line: Administer bypassing agent if not already given:
   • Recombinant FVIIa (eptacog alfa): 90 μg/kg, repeat every 2-3 hours as needed 1
   • Avoid APCC in emicizumab-treated patients due to thrombotic risk; if absolutely necessary, do not exceed 100 U/kg in first 24 hours 1

Critical Safety Considerations

Thrombotic Risk

Never violate the boxed warning regarding concomitant use of APCC with emicizumab 1, 4:

• Risk of thrombosis and thrombotic microangiopathy exists 1
• If APCC must be used, restrict dosing to median cumulative dose of 10.9 U/kg per bleed (IQR 8.6-14.5 U/kg) 1
• Total dose should not exceed 100 U/kg in first 24 hours 1

Alternative Bypassing Agents

Eptacog beta may be considered as an alternative to eptacog alfa, though less clinical experience exists 1:

• In vitro data suggests safety with emicizumab 1
• Not licensed for surgical use in some countries but clinical data exists 1

Common Pitfalls to Avoid

• Do not assume all extractions require factor replacement; many low-risk procedures succeed with local measures alone 2
• Do not fail to document current inhibitor status before the procedure 4
• Do not use APCC as first-line bypassing agent in emicizumab-treated patients 1
• Do not extract more than 3 teeth per visit to minimize bleeding risk 3
• Do not omit mouth splint application, which was used in 84-100% of successful cases 2
• Do not discharge patients without clear instructions about the 3-day high-risk bleeding window 6