PB0691 - Inhibitor Eradication Strategies in Patients with Non-Severe Hemophilia A

Background: The cumulative incidence of a factor VIII inhibitor can be as high as 13.3% in patients with non-severe hemophilia A (NSHA) [1]. Despite having a profound clinical impact with an almost 10-fold increase in annualized bleeding rate, evidence for optimal inhibitor eradication strategy remains scarce [1, 2]. Practice patterns vary greatly between different institutions and options for inhibitor eradication include immune tolerance induction (ITI), immunosuppressive (IS) agents, and watchful waiting without re-exposure to product [3]. We present a cohort of 5 patients with NSHA who developed clinically significant FVIII inhibitor with severe bleeding, that was successfully eradicated with ITI.

Aims: Emphasize the importance of inhibitor eradication strategies in patients with NSHA who develop severe bleeding phenotypes.

Methods: We conducted a retrospective chart review utilizing our institutional clinical database to identify patients with NSHA who developed factor VIII inhibitor. Baseline demographics, clinical variables along with outcomes data were captured.

Results: Five NSHA patients with FVIII inhibitor were identified; age range 3-41 years. Baseline factor VIII ranged between 3 to 19%. Four of five patients developed a high-titer inhibitor with >5 Bethesda Unit (BU); all patients developed severe hemophilia phenotype with FVIII < 1%. Severe bleeding was noted in our entire cohort, including epistaxis, flank hematoma, compartment syndrome of arm and calf, hemarthrosis of elbow and palmar pseudo-aneurysm. Hemostasis support was achieved using Hemlibra, FEIBA and Novoseven in 2, 3 and 4 patients, respectively. ITI was initiated with standard half-life (SHL) factor products in all patients; 3/5 patients had successful resolution of the inhibitor. The two patients who displayed suboptimal response to SHL factor were switched to an extended half-life product, achieving inhibitor eradication thereafter.

Conclusion(s): Information from our clinical cohort adds evidence for the successful use of ITI for eradication of inhibitor in NSHA patients.