Long-term course of anti-factor VIII antibody in patients with hemophilia A at a single center

Ki Young Yoo; Sang Chun Joo; Yong Mook Choi

doi:10.5045/br.2016.51.1.37

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Original Article

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Blood Res 2016; 51(1):

Published online March 31, 2016

https://doi.org/10.5045/br.2016.51.1.37

Long-term course of anti-factor VIII antibody in patients with hemophilia A at a single center

Ki Young Yoo^*, Sang Chun Joo, and Yong Mook Choi

Author Info. +

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

Received: November 27, 2015; Revised: January 29, 2016; Accepted: February 4, 2016

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

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.

Methods

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).

Results

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.

Conclusion

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

Article

Original Article

Blood Res 2016; 51(1): 37-43

Published online March 31, 2016 https://doi.org/10.5045/br.2016.51.1.37

Long-term course of anti-factor VIII antibody in patients with hemophilia A at a single center

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

Received: November 27, 2015; Revised: January 29, 2016; Accepted: February 4, 2016

Abstract

Background

Methods

Results

Conclusion

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

Abstract

Fig 1.

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Figure 1.

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.

Blood Research 2016; 51: 37-43https://doi.org/10.5045/br.2016.51.1.37

Fig 2.

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Figure 2.

Inhibitor status according to hemophilia A phenotypes. The severer phenotypes patients have, the more frequent inhibitors the patients developed (P<0.001). However the proportion of persistent inhibitors to transient inhibitors was not significantly higher in severe patients in comparison with the mild and moderate patients (P=0.221). Abbreviations: PWH, patient with hemophilia; INH, inhibitor.

Blood Research 2016; 51: 37-43https://doi.org/10.5045/br.2016.51.1.37

Fig 3.

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Figure 3.

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 (P=0.001).

Blood Research 2016; 51: 37-43https://doi.org/10.5045/br.2016.51.1.37

Fig 4.

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Figure 4.

Number of patients with persistent and transient inhibitors and the percentage of transient inhibitors, according to the peak inhibitor level.

Blood Research 2016; 51: 37-43https://doi.org/10.5045/br.2016.51.1.37

Table 1 Characteristics of patients with inhibitors against factor VIII.

^a)Number of patients that could be investigated for each variable. ^b)95% CI..

Abbreviations: INH, inhibitor; BU, Bethesda unit; CI, confidence interval..

Table 2 Long-term follow up of patients with transient inhibitors against factor VIII.

^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..

Table 3 Characteristics of patients treated with recurrent factor VIII inhibitors (N=71).

^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..

Table 4 Anti-FVIII inhibitor development by <italic>F8</italic> gene mutation.

^a)Cases: Combined persistent inhibitor and transient inhibitor patients. ^b)Controls: Inhibitor(-) patients. ^c)Fisher's exact test. Abbreviation: CI, confidence interval..