Non-Genetic Risk Factors for The Formation of Factor VIII Inhibitors in Hemophilia A Patients in RSUD Dr. Soetomo
DOI:
https://doi.org/10.24293/ijcpml.v26i1.1400Keywords:
Hemophilia, Factor VIII, Factor VIII InhibitorAbstract
Neutralizing alloantibodies (inhibitors) is one of the complications that affect the morbidity and quality of life of hemophilia patient and can be caused by multifactorials. Genetic and inhibitors examination are not routine and expensive. Therefore, identification of non-genetic factors is important to predict the formation of inhibitors.To analyze non-genetic risk factors for the formation of factor VIII inhibitors in children with Hemophilia A.
A cross-sectional study of hemophilia children aged 1-18 years at the pediatric hematology oncology outpatient clinic of Dr. Soetomo hospital in March-April 2018. Factors analyzed included the severity of hemophilia, early age of diagnosis, initial age of therapy, type of replacement therapy, frequency of factor VIII administration, and severity of bleeding by bleeding score. Statistical analysis using Chi square, Fisher, ANOVA and logistic regression analysis.
A total of 29 children were evaluated, 7/29 mild, 15/29 moderate, and 7/29 severe hemophilia. Inhibitors were found in 11/29 subjects, 7/11 low (1-5 BU) and 4/11 high titer (> 5 BU). The initial age of diagnosis ≤ 1 year is associated with the formation of factor VIII inhibitors (OR 8.75; 95% CI = 1.5-50.2; p = 0.015). Severity of hemophilia, early age of therapy, type of replacement therapy, frequency of therapy, and bleeding score was not significantly associated with the formation of factor VIII inhibitors.
The initial age of diagnosis less than 1 year is a significant risk factor for the formation of factor VIII inhibitors.
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References
Harijadi, Djajadiman G, Arwin A, Akib. The prevalence of factor VIII inhibitor in patients with severe hemophilia-A and its clinical characteristics. Paediatrica Indonesiana. 2005;45(7): 177-82.
Yantie VK dan Ariawati K. Inhibitor Pada Hemofilia. Medicina. 2002; 43(1): 31-6.
Aznar J, Moret AFFI, Vila C, Cabrera N, Mesa E, Bonanad S. Inhibitor development after switching of FVIII with severe haemophilia A. Haemophilia. 2014;20(5):624-9.
Witmer C dan Young G. Factor VIII inhibitors in hemophilia A: rationale and latest evidence. Ther Adv Hematol.2013; 4(1):59-72.
Gomez K, Klamroth R, Mahlangu J, Mancuso M, Mingot M, Ozelo M. Key issues in inhibitor management in patients with haemophilia. Blood Transfus. 2014; 12(1): 319-29.
Saifudin, Achmad, h, Reniarti. Faktor Risiko Non-genetik Inhibitor Faktor VIII pada Pasien Hemofilia A. Sari Pediatri. 2015; 17(2):119-23.
Septarini A and Windiastuti E. Terapi profilaksis versus on-demand pada pasien hemofilia berat dengan hemartrosis. Sari Pediatri. 2010;11(5):311-6.
Simatupang G, Windiastuti E, Oswari H. Faktor risiko timbulnya inhibitor faktor VIII pada anak dengan hemofilia A. Sari Pediatri. 2013;14(5):1-7.
Dekoven M, Wisniewski T, Petrilla A, Holot N, Lee W, Cooper D, Von Mackensen S. Health-related quality of life in haemophilia patients with inhibitors and their caregivers. Haemophilia. 2013;19(2): 287-93.
Astermark J. Why do inhibitors develop? principles of and factors influencing the risk for inhibitor development in haemophilia. Haemophilia. 2006;12(3):52–60.
Genderen FV, Meeteren NV, Bom JVD, Heijnen L, Kleijn PD, Berg HVD, Helders PJ. Functional consequences of haemophilia in adults: the development of the haemophilia activities list. Haemophilia. 2004;10(5): 565-71.
Gomez K, Klamroth R, Mahlangu J, Mancuso M, Mingot M, Ozelo M. Key issues in inhibitor management in patients with haemophilia. Blood Transfus. 2014;12(1): 319-29.
Bagheri S, Beheshtipoor N, Rambod M, Karimi M, Zare N dan Hashemi F. The quality of life of children with hemophilia in Shiraz, Iran. Ijcbnm. 2013;1(2): 1-10.
World Federation of Hemophilia Treatment Guidelines Working Group. Guidelines for the management of hemophilia. Montreal: Blackwell Publishing Ltd. 2012. pp.1-73.
Kreuz W and Ettingshausen C. Inhibitors In Patients With Haemophilia A. Thromb Res. 2014;134 (1):22-6.
Hay C, Palmer B dan Chalmers E. Incidence of factor VIII inhibitors throughout life in severe hemophilia A in The United Kingdom. Blood. 2011;117(23): 6367-70.
Gouw SC, Bom JGvd dan Berg Mv.. Treatment-related risk factors of inhibitor development in previously untreated patients with hemophilia A: the CANAL cohort study. Blood. 2007;109:4648–54.
Berg HVD. Risk of inhibitor development in children with haemophilia A. European Haematology Review. 2007;1(1):8-10.
Ragni M, Ojeifo O, Feng J. Risk factors for inhibitor formation in haemophilia: a prevalent case-control study. Haemophilia. 2009;15(5): 1074-82.
Lacroix-Desmazes S, Misra N, Bayry J, Artaud C, Drayton B, Kaveri S, Kazatchkine. Pathophysiology of inhibitors to factor VIII in patients with haemophilia A. Haemophilia.2002;8(3):273-9.
Ma AD and Carrizosa D. Acquired Faktor VIII Inhibitors: Pathophysiology And Treatment. Hematology Am Soc Hematol Educ Program. 2006;1:432-7.
Chalmers E, Brown S, Keeling D. Early factor VIII exposure and subsequent inhibitor development in children with severe hemophilia A. Hemophilia. 2007;13(1):149–55.
Goudemand J, Rothschild C, Demiguel V. Influence of the type of factor VIII concentrate on the incidence of factor VIII inhibitors in previously untreated patients with severe hemophilia A. Blood. 2006;107(1):46-51.
Gallucci dan Matzinger, P. Danger signals: SOS to the immune system. Curr Opin Immunol. 2001;13:114–9.
Kono, H.and Rock, K. How dying cells alert the immune system to danger. Nat Rev Immuno. 2008;8:279–9.
Matzinger, P. The danger model: a renewed sense of self. Science. 2002;296:301-5.
Elbatarny M, Mollah S, Grabell. Normal range of bleeding scores for the ISTH-BAT: adult and pediatric data from the merging project. Haemophilia. 2014;20(6): 831–5.
Shahriari M and Karimi M. Are bleeding scores predicting severity and outcome in hemophilia and rare bleeding disorders?. Blood. 2016;128:4801.
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