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血友病A的治疗进展
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Abstract:
血友病A是一种先天性出血性疾病。治疗目标是防止出血，降低与关节损伤有关的长期并发症的风险，并通过维持适当的因子VIII [FVIII]水平来减少出血并改善生活质量。近年来，血友病的治疗有了巨大的突破。在此，我们对血友病A的治疗进行了回顾，发现替代疗法的改变使血友病患者的出血率显著下降，但抑制剂的问题也日益凸显，此外，各种新型治疗方式也纷纷涌现出来。例如延长半衰期的凝血因子产品、模拟FVIII凝血功能的双特异性抗体和基因治疗等，为血友病的治疗带来新的曙光。同时也讨论了如何更好地从我国实际情况出发贯彻落实血友病综合关怀模式。
Haemophilia A is a congenital bleeding disorder. The therapeutic goal is to prevent bleeding, reduce the risk of long-term complications associated with joint damage, and reduce bleeding and improve the quality of life by maintaining the appropriate level of Factor VIII [FVIII]. In recent years, there have been tremendous breakthroughs in the treatment of haemophilia. Here we review the chang-ing treatment of haemophilia A, the transition of alternative treatment modes evidently decreased the incidence of haemophilia, but inhibitor issues were also gradually highlighted. In addition, var-ious new treatment methods have also emerged, such as extended half-life clotting factor products, dual specific antibodies to mimic the coagulation function of FVIII and gene therapy, bringing a new light to the treatment of haemophilia. At the same time, how to better implement the comprehen-sive care model of haemophilia from the actual situation of our country has also been discussed.
| [1] | Mannucci, P.M. and Tuddenham, E.G.D. (2001) The Hemophilias—From Royal Genes to Gene Therapy. New England Journal of Medicine, 344, 1773-1779. https://doi.org/10.1056/NEJM200106073442307 |
| [2] | 杨仁池. 中国血友病管理指南(2021年版) [M]. 北京: 中国协和医科大学出版社, 2021. |
| [3] | 程彦, 房云海, 张心声. 血友病救助体系的现状和探讨[J]. 罕见病研究, 2022, 1(4): 375-379. |
| [4] | 温红, 郭碧赟. 长期小剂量凝血因子VIII预防重度血友病A患儿关节出血的疗效与相关因素分析[J]. 中国小儿血液与肿瘤杂志, 2013, 18(1): 35-38. |
| [5] | Acharya, S.S. (2016) Advances in Hemophilia and the Role of Current and Emerging Prophylaxis. The American Journal of Managed Care, 22, 116-125. |
| [6] | Nilsson, I.M., Berntorp, E., L？fqvist, T. and Pettersson, H. (1992) Twenty-Five Years’ Expe-rience of Prophylactic Treatment in Severe Haemophilia A and B. Journal of Internal Medicine, 232, 25-32.
https://doi.org/10.1111/j.1365-2796.1992.tb00546.x |
| [7] | Manco-Johnson, M.J., Abshire, T.C., Shapiro, A.D., et al. (2007) Prophylaxis versus Episodic Treatment to Prevent Joint Disease in Boys with Severe Hemophilia. New Eng-land Journal of Medicine, 357, 535-544.
https://doi.org/10.1056/NEJMoa067659 |
| [8] | Gringeri, A., Lundin, B., Von Mackensen, S., Mantovani, L., Man-nucci, P.M. and ESPRIT Study Group (2011) A Randomized Clinical Trial of Prophylaxis in Children with Hemophilia A (The Esprit Study). Journal of Thrombosis and Haemostasis, 9, 700-710. https://doi.org/10.1111/j.1538-7836.2011.04214.x |
| [9] | Berntorp, E. (2013) History of Prophylaxis. Haemophilia, 19, 163-165. https://doi.org/10.1111/hae.12100 |
| [10] | 吴润晖. 中国儿童血友病专家指导意见(2017年) [J]. 中国实用儿科杂志, 2017, 32(1): 11-15. |
| [11] | 王梦媛, 姚敏, 万丹丹, 等. 187例血友病患儿关节状况与生活质量分析[J]. 浙江医学, 2017, 39(9): 736-739. |
| [12] | 黄昆, 陈振萍, 吴润晖. 影响血友病A患者FVIII药代动力学参数的相关因素[J]. 血栓与止血学, 2019, 25(5): 897-900. |
| [13] | Collins, P.W., Fischer, K., Morfini, M., et al. (2011) Implica-tions of Coagulation Factor VIII and IX Pharmacokinetics in the Prophylactic Treatment of Haemophilia. Haemophilia, 17, 2-10.
https://doi.org/10.1111/j.1365-2516.2010.02370.x |
| [14] | Peters, R. and Harris, T. (2018) Advances and Innovations in Haemophilia Treatment. Nature Reviews Drug Discovery, 17, 493-508. https://doi.org/10.1038/nrd.2018.70 |
| [15] | Pipe, S.W., Montgomery, R.R., Pratt, K.P., Lenting, P.J. and Lillicrap, D. (2016) Life in the Shadow of a Dominant Partner: The FVIII-VWF Association and Its Clinical Implications for Hemo-philia A. Blood, 128, 2007-2016.
https://doi.org/10.1182/blood-2016-04-713289 |
| [16] | Pestel, S., Beltz, H.W., Claar, P., et al. (2020) FVIII Half-Life Extension by Coadministration of a D’D3 Albumin Fusion Protein in Mice, Rabbits, Rats, and Monkeys. Blood Advanc-es, 4, 1870-1880.
https://doi.org/10.1182/bloodadvances.2019000999 |
| [17] | Peyvandi, F., Garagiola, I. and Young, G. (2016) The Past and Future of Haemophilia: Diagnosis, Treatments, and Its Complications. Lancet, 388, 187-97. https://doi.org/10.1016/S0140-6736(15)01123-X |
| [18] | 中华医学会血液学分会血栓与止血学组, 中国血友病协作组. 血友病诊断与治疗中国专家共识(2017年版) [J]. 中华血液学杂志, 2017, 38(5): 364-370. |
| [19] | Benson, G., Auerswald, G., Elezovi？, I., et al. (2012) Immune Tolerance Induction in Patients with Severe Hemophilia with Inhibitors: Expert Panel Views and Recommendations for Clinical Practice. European Journal of Haematology, 88, 371-379. https://doi.org/10.1111/j.1600-0609.2012.01754.x |
| [20] | Escuriola Ettingshausen, C. and Sidonio Jr., R.F. (2021) Design of an International Investigator-Initiated Study on Modern Treatment of Inhibitor-Positive Patients with Haemo-philia a (Motivate). Therapeutic Advances in Hematology, 12, Article ID: 20406207211032452. https://doi.org/10.1177/20406207211032452 |
| [21] | Hay, C.R. and DiMichele, D.M. (2012) The Principal Results of the International Immune Tolerance Study: A Randomized Dose Comparison. Blood, 119, 1335-1344. https://doi.org/10.1182/blood-2011-08-369132 |
| [22] | Shima, M., Hanabusa, H., Taki, M., et al. (2017) Long-Term Safety and Prophy-Lactic Efficacy of Once-Weekly Subcutaneous Administration ofACE910 in Japanese Hemophilia A Patients with and without FVIII Inhibitors: Interim Results of the Extension Study of a Phase 1 Study. Journal of Thrombosis and Haemostasis, 13, AS017. |
| [23] | Nogami, K. (2016) [A Bispecific Antibody Mimicking Factor Viii in Hemophilia a Therapy]. Rinsho Ketsueki, 57, 709-714. (In Japanese) |
| [24] | Dunbar, C.E., High, K.A., Joung, J.K., et al. (2018) Gene Therapy Comes of Age. Science, 359, eaan4672.
https://doi.org/10.1126/science.aan4672 |
| [25] | Poisson, J., Lemoinne, S., Boulanger, C., et al. (2017) Liver Sinusoi-dal Endothelial Cells: Physiology and Role in Liver Diseases. Journal of Hepatology, 66, 212-227. https://doi.org/10.1016/j.jhep.2016.07.009 |
| [26] | Dimichele, D., Miller, F.G. and Fins, J.J. (2003) Gene Therapy Ethics and Haemophilia: An Inevitable Therapeutic Future? Haemophilia, 9, 145-152. https://doi.org/10.1046/j.1365-2516.2003.00725.x |
| [27] | UK Haemophilia Centre Doctors’ Organisation Working Party (2004) Gene Therapy Trials in the Uk: Is Haemophilia a Suitable ‘Model’? Clinical Medicine Journal, 4, 54-56. https://doi.org/10.7861/clinmedicine.4-1-54 |
| [28] | Shirley, J.L., de Jong, Y.P., Terhorst, C. and Herzog, R.W. (2020) Immune Responses to Viral Gene Therapy Vectors. Molecular Therapy, 28, 709-722. https://doi.org/10.1016/j.ymthe.2020.01.001 |
| [29] | Colella, P., Ronzitti, G. and Mingozzi, F. (2018) Emerging Issues in AAV-Mediated in Vivo Gene Therapy. Methods & Clinical Development, 8, 87-104. https://doi.org/10.1016/j.omtm.2017.11.007 |
| [30] | George, L.A., Monahan, P.E., Eyster, M.E., et al. (2021) Multi-year Factor VIII Expression after AAV Gene Transfer for Hemophilia A. New England Journal of Medicine, 385, 1961-1973. https://doi.org/10.1056/NEJMoa2104205 |
| [31] | 刘国青, 王海红, 吴润晖, 等. 血友病的家庭治疗[J]. 血栓与止血学, 2015, 21(5): 326-327, 333. |
| [32] | Smith, P.S. and Levine, P.H. (1984) The Benefits of Comprehensive Care of Hemophilia: A Five-Year Study of Outcomes. American Journal of Public Health, 74, 616-617. https://doi.org/10.2105/AJPH.74.6.616 |
| [33] | Mahony, B.O., Savini, L., Hara, J.O. and Bok, A. (2017) Haemophilia Care in Europe—A Survey of 37 Countries. Haemophilia, 14, 216-224. https://doi.org/10.1111/hae.13263 |
| [34] | 吴心怡, 王旭梅, 甄英姿, 王春立, 张娴. 儿童血友病家庭治疗开展现状调查[J]. 护理研究, 2016, 30(33): 4192-4195. |
| [35] | 孟莎, 刘民. 将艾滋病/性病预防服务纳入城市社区卫生服务案例研究[J]. 中国全科医学, 2009, 12(11): 1037-1038. |
| [36] | Evatt, B.L., Black, C., Batorova, A., Street, A. and Srivastava, A. (2004) Comprehensive Care for Haemophilia around the World. Haemophilia, 10, 9-13. https://doi.org/10.1111/j.1365-2516.2004.01010.x |
