Blood Res 2019; 54(3):
Published online September 30, 2019
https://doi.org/10.5045/br.2019.54.3.204
© The Korean Society of Hematology
Correspondence to : Chur Woo You, M.D.
Department of Pediatrics, Eulji University School of Medicine, 95 Dunsanseo-ro, Seo-gu, Daejeon 35233, Korea
E-mail: YCW1@eulji.ac.kr
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.
Risk factors for the development of inhibitors in previously untreated patients (PUPs) have been reported; this is not the case in previously treated patients (PTPs) owing to fewer studies. Risk factors may differ for the development of PTP versus PUP inhibitors. We aimed to identify risk factors for PTP inhibitor development.
Participants were patients at a hemophilia treatment center in Korea with current or past history of factor VIII or factor IX alloantibodies. Observed inhibitors were classified as PUP or PTP inhibitors based on the cumulative number of exposure days. We compared the type and severity of hemophilia, mutation type, and family history of inhibitor between PUPs and PTPs. Events within 3 months before the first inhibitor detection, such as change of the factor concentrate used, short-term high exposure or continuous infusion of factor concentrate, history of surgery, infection, diagnosis of cancer, use of immunosuppressive or immunomodulator agents, and vaccination were compared between PUPs and PTPs.
We observed 5 PUP inhibitors and 5 PTP inhibitors in 115 patients with hemophilia A. Events that might be related to the development of inhibitors within 3 months prior to the first inhibitor detection were observed in all 5 PTPs. On the contrary, no such events were observed in any PUPs. The observed events included a change in the factor concentrate used, subsequent chemotherapy, and short-term high exposure to factor concentrates for controlling hemorrhage and surgeries.
Our results suggest a greater role of nongenetic factors in PTP inhibitor development.
Keywords Hemophilia A, Previously treated patient, Inhibitor, Risk factor
Blood Res 2019; 54(3): 204-209
Published online September 30, 2019 https://doi.org/10.5045/br.2019.54.3.204
Copyright © The Korean Society of Hematology.
Ju Young Kim, Chur Woo You
Department of Pediatrics, Eulji University School of Medicine, Daejeon, Korea
Correspondence to:Chur Woo You, M.D.
Department of Pediatrics, Eulji University School of Medicine, 95 Dunsanseo-ro, Seo-gu, Daejeon 35233, Korea
E-mail: YCW1@eulji.ac.kr
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.
Risk factors for the development of inhibitors in previously untreated patients (PUPs) have been reported; this is not the case in previously treated patients (PTPs) owing to fewer studies. Risk factors may differ for the development of PTP versus PUP inhibitors. We aimed to identify risk factors for PTP inhibitor development.
Participants were patients at a hemophilia treatment center in Korea with current or past history of factor VIII or factor IX alloantibodies. Observed inhibitors were classified as PUP or PTP inhibitors based on the cumulative number of exposure days. We compared the type and severity of hemophilia, mutation type, and family history of inhibitor between PUPs and PTPs. Events within 3 months before the first inhibitor detection, such as change of the factor concentrate used, short-term high exposure or continuous infusion of factor concentrate, history of surgery, infection, diagnosis of cancer, use of immunosuppressive or immunomodulator agents, and vaccination were compared between PUPs and PTPs.
We observed 5 PUP inhibitors and 5 PTP inhibitors in 115 patients with hemophilia A. Events that might be related to the development of inhibitors within 3 months prior to the first inhibitor detection were observed in all 5 PTPs. On the contrary, no such events were observed in any PUPs. The observed events included a change in the factor concentrate used, subsequent chemotherapy, and short-term high exposure to factor concentrates for controlling hemorrhage and surgeries.
Our results suggest a greater role of nongenetic factors in PTP inhibitor development.
Keywords: Hemophilia A, Previously treated patient, Inhibitor, Risk factor
Abbreviation: SH, severe hemophilia..
Abbreviations: EDs, exposure days; HA, hemophilia A; PTP, previously treated patient; PUP, previously untreated patient; SHA, severe hemophilia A; TR, transient inhibitor..
a)Events within 3 months before inhibitor detection..
No 1. Inhibitor detected at 32 years old and detected at 35 EDs after changing to EHL (extended half-life) FVIII..
No 2. Inhibitor detected at 65 years old after rectosigmoid cancer resection and chemotherapy..
No 3. Inhibitor detected at 55 years old after treatment for hemoperitoneum and liver laceration due to car accident, controlled with plasma-derived FVIII..
No 4. Inhibitor detected at 70 years old after knee arthroplasty..
No 5. Inhibitor detected at 33 years old after Rt with ankle osteotomy with synovectomy and prophylaxis for physical therapy..
Abbreviations: Dz, disease; EDs, exposure days; EHL, extended half-life; FMHX, familial history of inhibitor; HR, high responding; Ihn, inhibitor; Inv, inversion; LR, low responding; PT, physical therapy; SH, severity of hemophilia; SHA, severe hemophilia A; TR, transient inhibitor..
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