Blood Res 2016; 51(1):
Published online March 31, 2016
https://doi.org/10.5045/br.2016.51.1.37
© The Korean Society of Hematology
Korea Hemophilia Foundation, Seoul, Korea.
Correspondence to : Correspondence to Ki Young Yoo, M.D., Ph.D. Korea Hemophilia Foundation 70, Saimdang-ro, Seocho-gu, Seoul 06641, Korea. gowho@hanmail.net
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.
Immune tolerance induction (ITI) can reduce inhibitors against factor VIII concentrates by 70-80%. In this study, we elucidated the characteristics of inhibitors and attempted to determine the proper indications and timing for ITI.
Subjects included hemophilia A patients registered at the Korea Hemophilia Foundation from 1991 through 2014. Inhibitors were classified as persistent and transient. Patients were classified into groups according to peak inhibitor titer: low (<2 BU/mL), moderate (2 to <5 BU/mL), high (5 to <10 BU/mL), and very high titer (≥10 BU/mL).
Overall, 350 (21.4%) of 1,634 hemophilia A patients developed inhibitors at least once. Of these, 100 (6.1%) and 250 (15.3%) patients developed persistent and transient inhibitors, respectively. For transient inhibitors, the median peak titer was 1.0 BU/mL, persistent for median of 11.0 months (10.0, 8.0, 13.0, and 19.0 months in the low, moderate, high, and very high titer transient inhibitor groups, respectively). Overall, 95.8% (215), 72.2% (17), 52.4% (21), and 21.7% (97) of patients in the low, moderate, high, and very high titer groups became inhibitor-negative spontaneously, without ITI.
Given the spontaneous disappearance of inhibitors and high cost of ITI, it is worthwhile to postpone ITI for 11 months unless the peak inhibitor titer is greater than 10 BU/mL.
Keywords Hemophilia A, Inhibitor, Longitudinal study
Blood Res 2016; 51(1): 37-43
Published online March 31, 2016 https://doi.org/10.5045/br.2016.51.1.37
Copyright © The Korean Society of Hematology.
Ki Young Yoo*, Sang Chun Joo, and Yong Mook Choi
Korea Hemophilia Foundation, Seoul, Korea.
Correspondence to: Correspondence to Ki Young Yoo, M.D., Ph.D. Korea Hemophilia Foundation 70, Saimdang-ro, Seocho-gu, Seoul 06641, Korea. gowho@hanmail.net
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.
Immune tolerance induction (ITI) can reduce inhibitors against factor VIII concentrates by 70-80%. In this study, we elucidated the characteristics of inhibitors and attempted to determine the proper indications and timing for ITI.
Subjects included hemophilia A patients registered at the Korea Hemophilia Foundation from 1991 through 2014. Inhibitors were classified as persistent and transient. Patients were classified into groups according to peak inhibitor titer: low (<2 BU/mL), moderate (2 to <5 BU/mL), high (5 to <10 BU/mL), and very high titer (≥10 BU/mL).
Overall, 350 (21.4%) of 1,634 hemophilia A patients developed inhibitors at least once. Of these, 100 (6.1%) and 250 (15.3%) patients developed persistent and transient inhibitors, respectively. For transient inhibitors, the median peak titer was 1.0 BU/mL, persistent for median of 11.0 months (10.0, 8.0, 13.0, and 19.0 months in the low, moderate, high, and very high titer transient inhibitor groups, respectively). Overall, 95.8% (215), 72.2% (17), 52.4% (21), and 21.7% (97) of patients in the low, moderate, high, and very high titer groups became inhibitor-negative spontaneously, without ITI.
Given the spontaneous disappearance of inhibitors and high cost of ITI, it is worthwhile to postpone ITI for 11 months unless the peak inhibitor titer is greater than 10 BU/mL.
Keywords: Hemophilia A, Inhibitor, Longitudinal study
Annual number of new registrants and patients with inhibitors registered in the Korea Hemophilia Foundation. The high proportion of patients with inhibitors are observed in the early 5 years, 2005 , 2009, 2010 and 2011.
Inhibitor status according to hemophilia A phenotypes. The severer phenotypes patients have, the more frequent inhibitors the patients developed (
Kaplan–Meier survival curve of transient inhibitors according to peak titer. The duration of inhibitor presence was longer in very high titer, transient inhibitor group than in other 3 groups (
Number of patients with persistent and transient inhibitors and the percentage of transient inhibitors, according to the peak inhibitor level.
a)Number of patients that could be investigated for each variable. b)95% CI..
Abbreviations: INH, inhibitor; BU, Bethesda unit; CI, confidence interval..
a)Number of patients that could be investigated for each variable. b)95% CI. c)Peak titer <2 BU/mL. d)Peak titer 2 to <5 BU/mL. e)Peak titer 5 to <10 BU/mL. f)Peak titer ≥10 BU/mL..
Abbreviations: INH, inhibitor; BU, Bethesda unit; CI, confidence interval..
a)Number of episodes that could be investigated for each variable. b)Range..
Abbreviations: EDs, exposure days; INH, inhibitor; BU, Bethesda unit; CI, confidence interval..
a)Cases: Combined persistent inhibitor and transient inhibitor patients. b)Controls: Inhibitor(-) patients. c)Fisher's exact test. Abbreviation: CI, confidence interval..
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Annual number of new registrants and patients with inhibitors registered in the Korea Hemophilia Foundation. The high proportion of patients with inhibitors are observed in the early 5 years, 2005 , 2009, 2010 and 2011.
|@|~(^,^)~|@|Inhibitor status according to hemophilia A phenotypes. The severer phenotypes patients have, the more frequent inhibitors the patients developed (
Kaplan–Meier survival curve of transient inhibitors according to peak titer. The duration of inhibitor presence was longer in very high titer, transient inhibitor group than in other 3 groups (
Number of patients with persistent and transient inhibitors and the percentage of transient inhibitors, according to the peak inhibitor level.