Is inhibitor level checking required for a patient with a history of inhibitors on emicizumab?

Inhibitor Monitoring in Emicizumab-Treated Patients with Prior Inhibitor History

Ongoing inhibitor monitoring is strongly recommended for patients with a history of inhibitors who are currently on emicizumab, as inhibitor status directly impacts the choice of bypassing agents for breakthrough bleeding management and surgical hemostasis. 1

Rationale for Continued Monitoring

Clinical Necessity for Treatment Decisions

• The presence of an inhibitor significantly impacts factor product choice for bleeding management, making ongoing monitoring essential even in tolerized patients on emicizumab 1
• When managing breakthrough bleeds or surgery in patients on emicizumab, clinicians must know the current inhibitor status to select appropriate bypassing agents and avoid contraindicated combinations 2
• Treaters must be familiar with and not violate the boxed warning regarding concomitant use of activated prothrombin complex concentrate (APCC) with emicizumab, which requires knowledge of current inhibitor status 2

Risk of Inhibitor Relapse

• In a pediatric cohort of tolerized patients who transitioned from FVIII prophylaxis to emicizumab, 11 of 12 patients (92%) maintained negative inhibitor titers at mean follow-up of 14.2 months, but one patient experienced inhibitor relapse with a peak titer of 2.5 BU/mL 1
• Five of 11 patients (45%) with negative inhibitor titers had detectable non-neutralizing anti-FVIII IgG4 antibodies, though none had detectable IgG1 antibodies 1
• A significant reduction of FVIII inhibitor levels was noted among inhibitor patients on emicizumab prophylaxis during longitudinal follow-up, suggesting dynamic changes in inhibitor status 3

Recommended Monitoring Approach

Appropriate Testing Methods

• Chromogenic FVIII inhibitor assays should be used to assess inhibitor status, as aPTT-based tests are not suitable for laboratory monitoring in patients treated with emicizumab 4, 5
• Only FVIII chromogenic assays based on bovine FIX and FX proteins can accurately measure FVIII levels in the presence of emicizumab 4
• The Bethesda unit level of inhibitor should be determined when assessing current inhibitor status 2

Monitoring Frequency and Timing

• Inhibitor monitoring should be performed periodically during emicizumab therapy, particularly before surgical procedures or invasive interventions 1, 4
• Testing is especially important when planning for breakthrough bleed management or surgery, as this determines whether FVIII concentrates, recombinant FVIIa, or APCC should be used 2
• For patients with prior high-responding inhibitors, more frequent monitoring may be warranted given the potential for relapse 1

Clinical Implications

Impact on Bleeding Management

• In patients on emicizumab prophylaxis, recombinant FVIIa is preferred for bleeding management due to potential thrombotic complications with concomitant APCC use 2
• However, APCC can still be used with restrictions on dosing and duration if inhibitor status is known and monitored 2
• For patients with low-titer inhibitors (<2 BU), higher doses of FVIII concentrates may be effective, but this requires current inhibitor level knowledge 2

Surgical Planning

• Knowledge of inhibitor status is critical for surgical hemostasis planning in patients on emicizumab, as bypassing agent selection and dosing depend on current inhibitor titers 2
• For major surgery, bypassing agents at doses balancing benefits and risks are recommended, which requires accurate inhibitor assessment 2

Common Pitfalls to Avoid

• Do not use aPTT-based assays for inhibitor testing in emicizumab-treated patients, as emicizumab interferes with these conventional coagulation tests 4
• Do not assume inhibitor status remains unchanged from pre-emicizumab baseline, as levels can decrease or occasionally relapse during therapy 1, 3
• Do not fail to document inhibitor status before surgical procedures, as this information is essential for the multidisciplinary surgical team 2