Blood Res.  2016 Mar;51(1):37-43. 10.5045/br.2016.51.1.37.

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

• Yoo KY
• Joo SC
• Choi YM

• KMID: 2172743
• DOI: http://doi.org/10.5045/br.2016.51.1.37

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.

Keyword

Hemophilia A; Inhibitor; Longitudinal study

MeSH Terms

Factor VIII
Hemophilia A*
Humans
Immune Tolerance
Korea
Longitudinal Studies
Factor VIII

Figure

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  Fig. 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.

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  Fig. 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.

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  Fig. 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).

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  Fig. 4 Number of patients with persistent and transient inhibitors and the percentage of transient inhibitors, according to the peak inhibitor level.

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