Exploring Hemophilia: Understanding the Underlying Mechanisms, Diagnostic Strategies, and Therapeutic Advances
Keywords:
hemophilia, coagulation factors, blood disorder, genetic disorder, bleeding
Abstract
Hemophilia is an inherited blood disorder resulting in impaired blood clotting upon vascular damage due to defective or deficient coagulation factors. The three types of hemophilia are hemophilia A, hemophilia B, and hemophilia C, which result from the defect or deficiency of factor VIII, factor IX, and factor XI respectively. Hemophilia affects hundreds of millions of people worldwide, with the highest incidence in Asian countries including India, Bangladesh, and Indonesia. This review encompasses the epidemiology, etiology, pathophysiology, diagnosis, and treatment for hemophilia, and the literature sources were collected from other publications, including journal articles and books.
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References
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Castaman, G., & Matino, D. (2019). Hemophilia A and B: Molecular and clinical similarities and differences. Haematologica, 104(9), 1702–1709. https://doi.org/10.3324/haematol.2019.221093
Davidoff, A. M., & Nathwani, A. C. (2016). Genetic Targeting of the Albumin Locus to Treat Hemophilia. New England Journal of Medicine, 374(13), 1288–1290. https://doi.org/10.1056/NEJMcibr1600347
De Brasi, C., El-Maarri, O., Perry, D. J., Oldenburg, J., Pezeshkpoor, B., & Goodeve, A. (2014). Genetic testing in bleeding disorders. Haemophilia, 20, 54–58. https://doi.org/10.1111/hae.12409
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Hartmann, J., & Croteau, S. E. (2016). 2017 Clinical trials update: Innovations in hemophilia therapy. American Journal of Hematology, 91(12), 1252–1260. https://doi.org/10.1002/ajh.24543
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Iorio, A., Stonebraker, J. S., Chambost, H., Makris, M., Coffin, D., Herr, C., … for the Data and Demographics Committee of the World Federation of Hemophilia. (2019). Establishing the Prevalence and Prevalence at Birth of Hemophilia in Males: A Meta-analytic Approach Using National Registries. Annals of Internal Medicine, 171(8), 540. https://doi.org/10.7326/M19-1208
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Jeanpierre, E., Pouplard, C., Lasne, D., Le Cam Duchez, V., Eschwege, V., Flaujac, C., … Voyer, A. (2020). Factor VIII and IX assays for post‐infusion monitoring in hemophilia patients: Guidelines from the French BIMHO group (GFHT). European Journal of Haematology, 105(2), 103–115. https://doi.org/10.1111/ejh.13423
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Davidoff, A. M., & Nathwani, A. C. (2016). Genetic Targeting of the Albumin Locus to Treat Hemophilia. New England Journal of Medicine, 374(13), 1288–1290. https://doi.org/10.1056/NEJMcibr1600347
De Brasi, C., El-Maarri, O., Perry, D. J., Oldenburg, J., Pezeshkpoor, B., & Goodeve, A. (2014). Genetic testing in bleeding disorders. Haemophilia, 20, 54–58. https://doi.org/10.1111/hae.12409
Eckhardt, C. L., Van Velzen, A. S., Peters, M., Astermark, J., Brons, P. P., Castaman, G., … Fijnvandraat, K. (2013). Factor VIII gene (F8) mutation and risk of inhibitor development in nonsevere hemophilia A. Blood, 122(11), 1954–1962. https://doi.org/10.1182/blood-2013-02-483263
El Ekiaby, M., Burnouf, T., Goubran, H., Radosevich, M., & El Ekiaby, A. (2018). Role of the mini-pool cryoprecipitate technology for cost-saving and guarantee of local Factor VIII, Von Willebrand Factor and Fibrinogen product supply: Egypt experience. Annals of Blood, 3, 22–22. https://doi.org/10.21037/aob.2018.02.07
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Franchini, M., & Mannucci, P. M. (2011). Inhibitors of propagation of coagulation (factors VIII, IX and XI): A review of current therapeutic practice: Inhibitors of factors VIII, IX and XI. British Journal of Clinical Pharmacology, 72(4), 553–562. https://doi.org/10.1111/j.1365-2125.2010.03899.x
Goodeve, A. C. (2015). Hemophilia B: Molecular pathogenesis and mutation analysis. Journal of Thrombosis and Haemostasis, 13(7), 1184–1195. https://doi.org/10.1111/jth.12958
Gualtierotti, R., Pasca, S., Ciavarella, A., Arcudi, S., Giachi, A., Garagiola, I., … Peyvandi, F. (2022). Updates on Novel Non-Replacement Drugs for Hemophilia. Pharmaceuticals, 15(10), 1183. https://doi.org/10.3390/ph15101183
Hartmann, J., & Croteau, S. E. (2016). 2017 Clinical trials update: Innovations in hemophilia therapy. American Journal of Hematology, 91(12), 1252–1260. https://doi.org/10.1002/ajh.24543
Hirayama, A. B., Silva, A. K. C. D., Rocha, J. S., & Roberti, M. D. R. F. (2019). Prevalence of symptoms in hemophilia carriers in comparison with the general population: A systematic review. Hematology, Transfusion and Cell Therapy, 41(4), 349–355. https://doi.org/10.1016/j.htct.2019.02.006
Huether, S. E., McCance, K. L., Parkinson, C. F., Brashers, V. L., & Rote, N. S. (2022). Study Guide for Understanding Pathophysiology (5th ed.). Elsevier Saunders.
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Iorio, A., Stonebraker, J. S., Chambost, H., Makris, M., Coffin, D., Herr, C., … for the Data and Demographics Committee of the World Federation of Hemophilia. (2019). Establishing the Prevalence and Prevalence at Birth of Hemophilia in Males: A Meta-analytic Approach Using National Registries. Annals of Internal Medicine, 171(8), 540. https://doi.org/10.7326/M19-1208
Ishii, E. (2018). Hematological Disorders in Children: Pathogenesis and Treatment. Springer.
Jamil, M. A., Sharma, A., Nuesgen, N., Pezeshkpoor, B., Heimbach, A., Pavlova, A., … El-Maarri, O. (2019). F8 Inversions at Xq28 Causing Hemophilia A Are Associated With Specific Methylation Changes: Implication for Molecular Epigenetic Diagnosis. Frontiers in Genetics, 10, 508. https://doi.org/10.3389/fgene.2019.00508
Jankowska, K. I., McGill, J., Pezeshkpoor, B., Oldenburg, J., Sauna, Z. E., & Atreya, C. D. (2020). Further Evidence That MicroRNAs Can Play a Role in Hemophilia A Disease Manifestation: F8 Gene Downregulation by miR-19b-3p and miR-186-5p. Frontiers in Cell and Developmental Biology, 8, 669. https://doi.org/10.3389/fcell.2020.00669
Jayakrishnan, T., Shah, D., & Mewawalla, P. (2019). Hemophilia C: A Case Report With Updates on Diagnosis and Management of a Rare Bleeding Disorder. Journal of Hematology, 8(3), 144–147. https://doi.org/10.14740/jh522
Jeanpierre, E., Pouplard, C., Lasne, D., Le Cam Duchez, V., Eschwege, V., Flaujac, C., … Voyer, A. (2020). Factor VIII and IX assays for post‐infusion monitoring in hemophilia patients: Guidelines from the French BIMHO group (GFHT). European Journal of Haematology, 105(2), 103–115. https://doi.org/10.1111/ejh.13423
Kato, A., Asakai, R., Davie, E. W., & Aoki, N. (1989). Factor XI gene (F11) is located on the distal end of the long arm of human chromosome 4. Cytogenetic and Genome Research, 52(1–2), 77–78. https://doi.org/10.1159/000132844
Key, N. S. (2004). Inhibitors in congenital coagulation disorders: Review. British Journal of Haematology, 127(4), 379–391. https://doi.org/10.1111/j.1365-2141.2004.05168.x
Kitazawa, T., Igawa, T., Sampei, Z., Muto, A., Kojima, T., Soeda, T., … Hattori, K. (2012). A bispecific antibody to factors IXa and X restores factor VIII hemostatic activity in a hemophilia A model. Nature Medicine, 18(10), 1570–1574. https://doi.org/10.1038/nm.2942
Knobe, K., & Berntorp, E. (2011). Haemophilia and Joint Disease: Pathophysiology, Evaluation, and Management. Journal of Comorbidity, 1(1), 51–59. https://doi.org/10.15256/joc.2011.1.2
Knobe, K., & Berntorp, E. (2012). New treatments in hemophilia: Insights for the clinician. Therapeutic Advances in Hematology, 3(3), 165–175. https://doi.org/10.1177/2040620712440007
Kruse-Jarres, R., Kempton, C. L., Baudo, F., Collins, P. W., Knoebl, P., Leissinger, C. A., … Kessler, C. M. (2017). Acquired hemophilia A: Updated review of evidence and treatment guidance: KRUSE-JARRES et al. American Journal of Hematology, 92(7), 695–705. https://doi.org/10.1002/ajh.24777
Lannoy, N., & Hermans, C. (2010). The ‘royal disease’- haemophilia A or B? A haematological mystery is finally solved: THE ROYAL DIESEASE. Haemophilia, 16(6), 843–847. https://doi.org/10.1111/j.1365-2516.2010.02327.x
Mannucci, P. M. (2020). Hemophilia therapy: The future has begun. Haematologica, 105(3), 545–553. https://doi.org/10.3324/haematol.2019.232132
Mansouritorghabeh, H. (2015). Clinical and laboratory approaches to hemophilia a. Iranian Journal of Medical Sciences, 40(3), 194–205.
Mantik, M. F. J., Gunawan, S., & Wowiling, S. (2020). Knowledge about hemophilia among teachers of patients with hemophilia in Indonesia. Pediatric Hematology Oncology Journal, 5(3), 126–129. https://doi.org/10.1016/j.phoj.2020.06.003
Matuk-Villazon, O., Roberts, J. C., & Corrales-Medina, F. F. (2021). Hemophilia: The Past, the Present, and the Future. Pediatrics In Review, 42(12), 672–683. https://doi.org/10.1542/pir.2020-004143
Meeks, S. L., & Batsuli, G. (2016). Hemophilia and inhibitors: Current treatment options and potential new therapeutic approaches. Hematology, 2016(1), 657–662. https://doi.org/10.1182/asheducation-2016.1.657
Nathwani, A. C. (2019). Gene therapy for hemophilia. Hematology, 2019(1), 1–8. https://doi.org/10.1182/hematology.2019000007
Nogami, K., & Shima, M. (2019). New therapies using nonfactor products for patients with hemophilia and inhibitors. Blood, 133(5), 399–406. https://doi.org/10.1182/blood-2018-07-820712
Payne, A. B., Miller, C. H., Kelly, F. M., Soucie, J. M., & Hooper, W. C. (2013). The CDC Hemophilia A Mutation Project (CHAMP) Mutation List: A New Online Resource. Human Mutation, 34(2), E2382–E2392. https://doi.org/10.1002/humu.22247
Peyvandi, F., Kenet, G., Pekrul, I., Pruthi, R. K., Ramge, P., & Spannagl, M. (2020). Laboratory testing in hemophilia: Impact of factor and non‐factor replacement therapy on coagulation assays. Journal of Thrombosis and Haemostasis, 18(6), 1242–1255. https://doi.org/10.1111/jth.14784
Pipe, S. W., Montgomery, R. R., Pratt, K. P., Lenting, P. J., & Lillicrap, D. (2016). Life in the shadow of a dominant partner: The FVIII-VWF association and its clinical implications for hemophilia A. Blood, 128(16), 2007–2016. https://doi.org/10.1182/blood-2016-04-713289
Polderdijk, S. G. I., Adams, T. E., Ivanciu, L., Camire, R. M., Baglin, T. P., & Huntington, J. A. (2017). Design and characterization of an APC-specific serpin for the treatment of hemophilia. Blood, 129(1), 105–113. https://doi.org/10.1182/blood-2016-05-718635
Potgieter, J. J., Damgaard, M., & Hillarp, A. (2015). One-stage vs. Chromogenic assays in haemophilia A. European Journal of Haematology, 94, 38–44. https://doi.org/10.1111/ejh.12500
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Published
2025-03-19
How to Cite
Danisa, M., Maringka, S., Augusto, E., Catherine, A., Christian, M., Febriana, G., Wong, M. M., & Tjong, K. (2025). Exploring Hemophilia: Understanding the Underlying Mechanisms, Diagnostic Strategies, and Therapeutic Advances. Indonesian Journal of Life Sciences, 7(1), 59-74. https://doi.org/https://doi.org/10.54250/ijls.v7i1.187
Issue
Section
Life Science for Health and Wellbeing
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