Immune tolerance induction in patients with severe hemophilia A with inhibitors

Ji Eun Ryu; Young Shil Park; Ki Young Yoo; Kyoo Duck Lee; Yong-Mook Choi

doi:10.5045/br.2015.50.4.248

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Original Article

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Blood Res 2015; 50(4):

Published online December 31, 2015

https://doi.org/10.5045/br.2015.50.4.248

Immune tolerance induction in patients with severe hemophilia A with inhibitors

Ji Eun Ryu¹, Young Shil Park^1*, Ki Young Yoo², Kyoo Duck Lee³, and Yong-Mook Choi²

Author Info. +

¹Department of Pediatrics, Kyung Hee University Hospital at Gangdong, Kyung Hee University School of Medicine, Seoul, Korea.

²Korea Hemophilia Foundation, Seoul, Korea.

³Health Insurance Review & Assessment Service, Seoul, Korea.

Correspondence to : Correspondence to Young Shil Park, M.D., Ph.D. Department of Pediatrics, Kyung Hee University Hospital at Gangdong, 892, Dongnam-ro, Gangdong-gu, Seoul 05278, Korea. Tel: +82-2-440-6133, pysmd@khnmc.or.kr

Received: July 24, 2015; Revised: September 7, 2015; Accepted: November 4, 2015

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

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Abstract

Background

Inhibitory antibodies to factor VIII (FVIII) are an important complication when managing patients with hemophilia A. Immune tolerance induction (ITI) has been regarded as a useful method for eradicating inhibitors. We report the results of a retrospective study in Korean patients with hemophilia A who underwent ITI.

Methods

We reviewed the records of patients with hemophilia A with inhibitors who underwent ITI from March 2004 to December 2014. ITI was started with FVIII concentrates at 100 IU/kg, 3 times per week. The dose of FVIII was reduced according to the inhibitor titer and recovery of FVIII. Inhibitor elimination was defined as the time taken to achieve a negative inhibitor assay with no anamnestic response and normal FVIII recovery and/or normal half-life.

Results

In total, 17 patients with severe hemophilia A were evaluated. Complete tolerance was achieved in 14 of 17 patients (83%). The mean peak inhibitor titer before ITI was 38.4 BU/mL. The mean treatment duration was 26.2 months. The mean duration between inhibitor detection and ITI was 5.1 years in the complete tolerance group and 10.8 years in the partial tolerance and failed group.

Conclusion

This study shows that ITI can be an effective and well-tolerated method for eradicating inhibitors. Possible influencing factors for ITI success were age at the start of ITI treatment and duration after inhibitor detection. More research to provide further insight about other factors and conditions is needed.

Keywords Hemophilia A, Inhibitor, Immune tolerance induction

Article

Original Article

Blood Res 2015; 50(4): 248-253

Published online December 31, 2015 https://doi.org/10.5045/br.2015.50.4.248

Immune tolerance induction in patients with severe hemophilia A with inhibitors

Ji Eun Ryu¹, Young Shil Park^1*, Ki Young Yoo², Kyoo Duck Lee³, and Yong-Mook Choi²

¹Department of Pediatrics, Kyung Hee University Hospital at Gangdong, Kyung Hee University School of Medicine, Seoul, Korea.

²Korea Hemophilia Foundation, Seoul, Korea.

³Health Insurance Review & Assessment Service, Seoul, Korea.

Correspondence to:Correspondence to Young Shil Park, M.D., Ph.D. Department of Pediatrics, Kyung Hee University Hospital at Gangdong, 892, Dongnam-ro, Gangdong-gu, Seoul 05278, Korea. Tel: +82-2-440-6133, pysmd@khnmc.or.kr

Received: July 24, 2015; Revised: September 7, 2015; Accepted: November 4, 2015

Abstract

Background

Methods

Results

Conclusion

Keywords: Hemophilia A, Inhibitor, Immune tolerance induction

Abstract

Table 1 Patient demographics and clinical characteristics.

^a)The number of injection increased from 3 times a week to every day..

Abbreviations: CED, cumulative exposure days to FVIII; ID, inhibitor detection; ITI, immune tolerance induction; Int22inv., intron 22 inversion; Exon del, exon deletion; UK, unknown; HP, historical peak; FVIII, factor VIII; Pd, plasma-derived FVIII/von Willebrand factor; R, recombinant; CT, complete tolerance; PT, partial tolerance; F, failure..

Table 2 Comparison of ITI outcomes between complete tolerance group and partial tolerance and failure group.

^a)P value by t-test between complete tolerance group and partial tolerance and failure group..

Abbreviations: ITI, immune tolerance induction; ID, inhibitor detection; FVIII, factor VIII; pdVWF, plasma-derived von Willebrand factor..

Table 3 Bleeding events occurred before, during, and after ITI.

^a)Major bleeding refers to joint and muscle bleeding events. Other bleeding events refer to gastrointestinal, urogenital, skin, and gingival bleeding. ^b)One year before ITI. ^c)One year after ITI. ^d)P value by χ² comparing before, during, and after ITI..

Abbreviation: ITI, immune tolerance induction..