Immun Tolerance Induction in Hemophilia with Inhibitors: Istanbul Experience

Introduction: The development of inhibitors against factor VIII or IX is the most serious complication in hemophilia, occurring in approximately 30% and 5% of severe hemophilia A and B patients, respectively. Management of hemophilia with inhibitors presents certain challenges. The best treatment strategy for inhibitor eradication is immune tolerance induction (ITI). The aim of this study was to evaluate patients who were treated by ITI at our center.

Material-Method: A retrospective data collection and analysis of patients were obtained. Data from all subjects with Hemophilia A with inhibitors undergoing ITI between 1999 and 2017 were collected from Istanbul University Hemophilia Centre.

Results: Fifteen patients with severe Hemophilia A were enrolled in the study of whom 13 were eligible for analysis. After the exclusion of ineffective ITI treatments, median age of the beginning ITI was 10 years old (range:1,25-52), median maximum inhibitor titer before ITI was 30 BU (range:4.48-135) and during ITI was 3,4 BU (range:0-158.7). Median inhibitor titre was 1.25 BU (range:0-5.6) at the beginning of ITI. Median time interval between inhibitor development and starting of ITI was 5 years (range:0.58-22). In totally, 4 of the 12 patients (33.3%) had complete response, 2 of 12 (16.6%) had partial response and 2 of 12 (16.6%) had decreasing of inhibitor titer and ITI is going on. Four of the 12 patients (33.3%) had failure of ITI.

Conclusion: Management of hemophilia with inhibitors presents certain challenges. Immun tolerance induction is the best treatment model. But high-dose daily regimen ITI could not be given in Turkey due to high cost of treatment. Our results showed that low dose ITI could be a choice for patients with inhibitors.