<?xml version="1.0" encoding="UTF-8"?>
<!DOCTYPE root>
<article xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xmlns:ali="http://www.niso.org/schemas/ali/1.0/" article-type="other" dtd-version="1.2" xml:lang="en"><front><journal-meta><journal-id journal-id-type="publisher-id">Pediatric Hematology/Oncology and Immunopathology</journal-id><journal-title-group><journal-title xml:lang="en">Pediatric Hematology/Oncology and Immunopathology</journal-title><trans-title-group xml:lang="ru"><trans-title>Вопросы гематологии/онкологии и иммунопатологии в педиатрии</trans-title></trans-title-group></journal-title-group><issn publication-format="print">1726-1708</issn><issn publication-format="electronic">2414-9314</issn><publisher><publisher-name xml:lang="en">Fund Doctors, Innovations, Science for Children</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="publisher-id">624</article-id><article-id pub-id-type="doi">10.24287/1726-1708-2022-21-2-122-126</article-id><article-categories><subj-group subj-group-type="toc-heading" xml:lang="en"><subject>CLINICAL OBSERVATIONS</subject></subj-group><subj-group subj-group-type="toc-heading" xml:lang="ru"><subject>КЛИНИЧЕСКИЕ НАБЛЮДЕНИЯ</subject></subj-group><subj-group subj-group-type="article-type"><subject></subject></subj-group></article-categories><title-group><article-title xml:lang="en">Immune tolerance induction with a high-purity von Willebrand factor containing plasma-derived factor VIII concentrate in a child with hemophilia A with inhibitors</article-title><trans-title-group xml:lang="ru"><trans-title>Опыт проведения индукции иммунной толерантности плазматическим концентратом фактора свертывания VIII с высоким содержанием фактора Виллебранда у ребенка с ингибиторной формой гемофилии А</trans-title></trans-title-group></title-group><contrib-group><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0003-4384-6754</contrib-id><name-alternatives><name xml:lang="en"><surname>Zharkov</surname><given-names>P. A.</given-names></name><name xml:lang="ru"><surname>Жарков</surname><given-names>П. А.</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><bio xml:lang="en"><p><bold>Pavel A. Zharkov</bold>, Dr. Med. Sci., a hematologist at the Outpatient Department, Head of the Department of Hemostasis Disorder Research</p><p>1 Samory Mashela St., Moscow 117997</p></bio><bio xml:lang="ru"><p><bold>Жарков Павел Александрович</bold>, д-р мед. наук, врач-гематолог консультативного отделения, заведующий отделом патологии гемостаза</p><p>117997, Москва, ул. Саморы Машела, 1</p></bio><email>pavel.zharkov@fccho-moscow.ru</email><xref ref-type="aff" rid="aff1"/></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0003-4567-1871</contrib-id><name-alternatives><name xml:lang="en"><surname>Fedorova</surname><given-names>D. V.</given-names></name><name xml:lang="ru"><surname>Федорова</surname><given-names>Д. В.</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><bio xml:lang="en"><p>Moscow</p></bio><bio xml:lang="ru"><p>Москва</p></bio><xref ref-type="aff" rid="aff1"/></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-7817-8672</contrib-id><name-alternatives><name xml:lang="en"><surname>Erega</surname><given-names>E. P.</given-names></name><name xml:lang="ru"><surname>Ерега</surname><given-names>Е. П.</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><bio xml:lang="en"><p>Khabarovsk</p></bio><bio xml:lang="ru"><p>Хабаровск</p></bio><xref ref-type="aff" rid="aff2"/></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0001-5209-2099</contrib-id><name-alternatives><name xml:lang="en"><surname>Poletaev</surname><given-names>A. V.</given-names></name><name xml:lang="ru"><surname>Полетаев</surname><given-names>А. В.</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><bio xml:lang="en"><p>Moscow</p></bio><bio xml:lang="ru"><p>Москва</p></bio><xref ref-type="aff" rid="aff1"/></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-7534-3863</contrib-id><name-alternatives><name xml:lang="en"><surname>Seregina</surname><given-names>E. A.</given-names></name><name xml:lang="ru"><surname>Серегина</surname><given-names>Е. А.</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><bio xml:lang="en"><p>Moscow</p></bio><bio xml:lang="ru"><p>Москва</p></bio><xref ref-type="aff" rid="aff1"/><xref ref-type="aff" rid="aff3"/></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-2057-2036</contrib-id><name-alternatives><name xml:lang="en"><surname>Pshonkin</surname><given-names>A. V.</given-names></name><name xml:lang="ru"><surname>Пшонкин</surname><given-names>А. В.</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><bio xml:lang="en"><p>Moscow</p></bio><bio xml:lang="ru"><p>Москва</p></bio><xref ref-type="aff" rid="aff1"/></contrib></contrib-group><aff-alternatives id="aff1"><aff><institution xml:lang="en">Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology of Ministry of Healthcare of the Russian Federation</institution></aff><aff><institution xml:lang="ru">ФГБУ «Национальный медицинский исследовательский центр детской гематологии, онкологии и иммунологии им. Дмитрия Рогачева» Минздрава России</institution></aff></aff-alternatives><aff-alternatives id="aff2"><aff><institution xml:lang="en">A.K. Piotrovich Children's Regional Clinical Hospital of Ministry of Healthcare of the Khabarovsk Krai</institution></aff><aff><institution xml:lang="ru">КГБУЗ «Детская краевая клиническая больница им. А.К. Пиотровича» Министерства здравоохранения Хабаровского края</institution></aff></aff-alternatives><aff-alternatives id="aff3"><aff><institution xml:lang="en">Center for Theoretical Problems of Physicochemical Pharmacology, Russian Academy of Sciences</institution></aff><aff><institution xml:lang="ru">ФГБУН Центр теоретических проблем физико-химической фармакологии Российской академии наук</institution></aff></aff-alternatives><pub-date date-type="pub" iso-8601-date="2022-07-08" publication-format="electronic"><day>08</day><month>07</month><year>2022</year></pub-date><volume>21</volume><issue>2</issue><issue-title xml:lang="en"/><issue-title xml:lang="ru"/><fpage>122</fpage><lpage>126</lpage><history><date date-type="received" iso-8601-date="2022-06-25"><day>25</day><month>06</month><year>2022</year></date><date date-type="accepted" iso-8601-date="2022-06-25"><day>25</day><month>06</month><year>2022</year></date></history><permissions><copyright-statement xml:lang="en">Copyright ©; 2025, «D. Rogachev NMRCPHOI»</copyright-statement><copyright-statement xml:lang="ru">Copyright ©; 2025, ФГБУ «НМИЦ ДГОИ им. Дмитрия Рогачева» Минздрава России</copyright-statement><copyright-year>2025</copyright-year><copyright-holder xml:lang="en">«D. Rogachev NMRCPHOI»</copyright-holder><copyright-holder xml:lang="ru">ФГБУ «НМИЦ ДГОИ им. Дмитрия Рогачева» Минздрава России</copyright-holder><ali:free_to_read xmlns:ali="http://www.niso.org/schemas/ali/1.0/"/><license><ali:license_ref xmlns:ali="http://www.niso.org/schemas/ali/1.0/">https://creativecommons.org/licenses/by/4.0</ali:license_ref></license></permissions><self-uri xlink:href="https://hemoncim.com/jour/article/view/624">https://hemoncim.com/jour/article/view/624</self-uri><abstract xml:lang="en"><p>   Immune tolerance induction (ITI) is the principal method of inhibitor eradication in patients with hemophilia A. The existing guidelines generally recommend to start ITI with recombinant FVIII concentrates, but the presence of VWF in plasma-derived FVIII concentrates used for ITI may further influence the ITI success rate. A five-year-old male patient with hemophilia A withinhibitors started ITI at our Center. The patient's parents gave consent to the use of their child's data, including photographs, for research purposes and in publications. The patient had an inhibitor titer of 0.52 BU/mL at the start of the ITI and a historical inhibitor peak titer of 28 BU/mL. The ITI was started 3.5 years after the first inhibitor detection. We chose a plasma-derived VWF/FVIII containing concentrate (Haemate P) and started the ITI at a dose of 100 units FVIII/kg once per day using central venous access, as proposed in the protocol developed by the United Kingdom Haemophilia Centre Doctors’ Organization (UKHCDO). The inhibitor titer rose to 5.5 BU/mL on day 10 and became negative on day 25 of the ITI. The FVIII trough level measured 24 h after the last dose was &gt; 1 % on day 25. The patient discontinued prophylaxis with a bypassing agent. However, FVIII pharmacokinetics had not returned to normal yet, and the patient continued the ITI with the VWF/FVIII containing concentrate at the initial dose. We reassessed the parameters of FVIII pharmacokinetics 120, 270 and 300 days after the start of the ITI. The peak FVIII level, its half-life time and the trough level measured 24 h after the last dose gradually increased over time. On day 300, the half-life time was still less than 7 h (6 h), but the trough level at 24 h was as high as 12.6 %. So, the patient started tapering off the medicine (the dose was initially reduced to 75 units/kg once per day). No adverse events were observed during the 1 year of therapy. Starting from day 423, the patient was switched to prophylaxis with the concentrate administered at a dose of 50 IU/kg every other day. Here, we reported our experience with first-line ITI using the FVIII concentrate with a high content of VWF (Haemate P). A rapid decrease in the inhibitor titer and the normalization of the pharmacokinetic parameters of FVIII in the absence of significant bleeding or thrombotic complications were convincingly demonstrated. </p></abstract><trans-abstract xml:lang="ru"><p>   Индукция иммунной толерантности (ИИТ) является основным методом эрадикации ингибиторов у пациентов с гемофилией А. Высокое содержание фактора Виллебранда (ФВ) в плазматическом концентрате фактора VIII (FVIII) может иметь дополнительные преимущества в отношении достижения успеха ИИТ. Для проведения ИИТ в наш Центр обратился мальчик 5 лет с ингибиторной формой гемофилии. Родители пациента дали согласие на использование информации, в том числе фотографий ребенка, в научных исследованиях и публикациях. Титр ингибитора к FVIII составлял 0,52 БЕ/мл, исторический пик ингибитора 28 БЕ/мл. ИИТ начали через 3,5 года после первого обнаружения ингибитора. Для проведения ИИТ был использован концентрат FVIII с высоким содержанием ФВ (Гемате П). ИИТ была начата в режиме 100 МЕ/кг/сут по FVIII в соответствии с протоколом, предложенным United Kingdom Haemophilia Centre Doctors’ Organisation (UKHCDO), с использованием центрального венозного доступа. Титр ингибитора повысился до 5,5 БЕ/мл на 10-й день и стал отрицательным на 25-й день ИИТ. Значение активности FVIII &gt; 1 % было достигнуто на 25-й день терапии. Пациент прекратил профилактику шунтирующим препаратом. Однако фармакокинетика FVIII еще не вернулась к нормальным показателям, и пациент продолжил ИИТ с начальной дозой концентрата. Мы провели повторную оценку параметров фармакокинетики FVIII на 120-й, 270-й и 300-й дни от начала терапии. Пиковый уровень, период полувыведения и активность FVIII через 24 ч после введения препарата постепенно увеличивались с течением времени. На 300-й день период полувыведения был все еще меньше 7 ч (6 ч), активность FVIII через 24 ч от введения уже составляла 12,6 %. Таким образом, пациент начал снижение дозы (первоначально доза была снижена до 75 ЕД/кг 1 раз в сутки). Нежелательных явлений в течение 1 года терапии не наблюдалось. С 423-го дня пациент был переведен на профилактическое введение концентрата в режиме 50 МЕ/кг через день. Нами представлен собственный опыт проведения ИИТ первой линии с использованием концентрата FVIII с высоким содержанием ФВ (Гемате П). Убедительно продемонстрированы быстрое снижение титра ингибитора и нормализация фармакокинетических показателей FVIII в отсутствие значимых кровотечений и тромботических осложнений.</p></trans-abstract><kwd-group xml:lang="en"><kwd>children</kwd><kwd>hemophilia A</kwd><kwd>inhibitors</kwd><kwd>concentrate</kwd><kwd>von Willebrand</kwd><kwd>Haemate P</kwd></kwd-group><kwd-group xml:lang="ru"><kwd>дети</kwd><kwd>гемофилия А</kwd><kwd>ингибиторы</kwd><kwd>концентрат</kwd><kwd>фон Виллебранд</kwd><kwd>Гемате П</kwd></kwd-group><funding-group><funding-statement xml:lang="en">Not specified</funding-statement><funding-statement xml:lang="ru">Не указан</funding-statement></funding-group></article-meta></front><body></body><back><ref-list><ref id="B1"><label>1.</label><citation-alternatives><mixed-citation xml:lang="en">1. Hay C. R. M., Palmer B., Chalmers E., Liesner R., Mac Lean R., Rangarajan S., et al. Incidence of factor VIII inhibitors throughout life in severe hemophilia A in the United Kingdom. Blood 2011; 117 (23): 6367–70. DOI: 10.1182/blood-2010-09-308668</mixed-citation><mixed-citation xml:lang="ru">Hay C. R. M., Palmer B., Chalmers E., Liesner R., Mac Lean R., Rangarajan S., et al. Incidence of factor VIII inhibitors throughout life in severe hemophilia A in the United Kingdom. Blood 2011; 117 (23): 6367–70. DOI: 10.1182/blood-2010-09-308668</mixed-citation></citation-alternatives></ref><ref id="B2"><label>2.</label><citation-alternatives><mixed-citation xml:lang="en">2. Peyvandi F., Mannucci P. M., Garagiola I., El-Beshlawy A., Elalfy M., Ramanan V., et al. A Randomized Trial of Factor VIII and Neutralizing Antibodies in Hemophilia A. N Engl J Med 2016; 374 (21): 2054–64. DOI: 10.1056/nejmoa1516437</mixed-citation><mixed-citation xml:lang="ru">Peyvandi F., Mannucci P. M., Garagiola I., El-Beshlawy A., Elalfy M., Ramanan V., et al. A Randomized Trial of Factor VIII and Neutralizing Antibodies in Hemophilia A. N Engl J Med 2016; 374 (21): 2054–64. DOI: 10.1056/nejmoa1516437</mixed-citation></citation-alternatives></ref><ref id="B3"><label>3.</label><citation-alternatives><mixed-citation xml:lang="en">3. Fischer K., Lassila R., Peyvandi F., Calizzani G., Gatt A., Lambert Т., et al. Inhibitor development in haemophilia according to concentrate: Four-year results from the European haemophilia safety surveillance (EUHASS) project. Thromb Haemost 2015; 113 (5): 968–75. DOI: 10.1160/TH14-10-0826</mixed-citation><mixed-citation xml:lang="ru">Fischer K., Lassila R., Peyvandi F., Calizzani G., Gatt A., Lambert Т., et al. Inhibitor development in haemophilia according to concentrate: Four-year results from the European haemophilia safety surveillance (EUHASS) project. Thromb Haemost 2015; 113 (5): 968–75. DOI: 10.1160/TH14-10-0826</mixed-citation></citation-alternatives></ref><ref id="B4"><label>4.</label><citation-alternatives><mixed-citation xml:lang="en">4. Gouw S. C., VAN DEN Berg H. M., Fischer K., Auerswald, G., Carcao М., Chalmers Е., et al. Intensity of factor VIII treatment and inhibitor development in children with severe hemophilia A: The RODIN study. Blood 2013; 121 (20): 4046–55. DOI: 10.1182/blood-2012-09-457036</mixed-citation><mixed-citation xml:lang="ru">Gouw S. C., VAN DEN Berg H. M., Fischer K., Auerswald, G., Carcao М., Chalmers Е., et al. Intensity of factor VIII treatment and inhibitor development in children with severe hemophilia A: The RODIN study. Blood 2013; 121 (20): 4046–55. DOI: 10.1182/blood-2012-09-457036</mixed-citation></citation-alternatives></ref><ref id="B5"><label>5.</label><citation-alternatives><mixed-citation xml:lang="en">5. Kreuz W. The role of VWF for the success of immune tolerance induction. Thromb Res 2008; 122 Suppl 2: S7–S12. DOI: 10.1016/S0049-3848(08)70003-3</mixed-citation><mixed-citation xml:lang="ru">Kreuz W. The role of VWF for the success of immune tolerance induction. Thromb Res 2008; 122 Suppl 2: S7–S12. DOI: 10.1016/S0049-3848(08)70003-3</mixed-citation></citation-alternatives></ref><ref id="B6"><label>6.</label><citation-alternatives><mixed-citation xml:lang="en">6. Escuriola Ettingshausen C., Kreuz W. A review of immune tolerance induction with Haemate P in haemophilia A. Haemophilia 2014; 20 (3): 333–9. DOI: 10.1111/hae.12288</mixed-citation><mixed-citation xml:lang="ru">Escuriola Ettingshausen C., Kreuz W. A review of immune tolerance induction with Haemate P in haemophilia A. Haemophilia 2014; 20 (3): 333–9. DOI: 10.1111/hae.12288</mixed-citation></citation-alternatives></ref><ref id="B7"><label>7.</label><citation-alternatives><mixed-citation xml:lang="en">7. Rothschild C., D’oiron R., Borel-derlon A., Gruel Y., Navarro R., Negrier C. Use of Haemate® P as immune tolerance induction in patients with severe haemophilia A who failed previous induction attempts: A multicentre observational study. Haemophilia 2013; 19 (2): 281–6. DOI: 10.1111/hae.12018</mixed-citation><mixed-citation xml:lang="ru">Rothschild C., D’oiron R., Borel-derlon A., Gruel Y., Navarro R., Negrier C. Use of Haemate® P as immune tolerance induction in patients with severe haemophilia A who failed previous induction attempts: A multicentre observational study. Haemophilia 2013; 19 (2): 281–6. DOI: 10.1111/hae.12018</mixed-citation></citation-alternatives></ref><ref id="B8"><label>8.</label><citation-alternatives><mixed-citation xml:lang="en">8. Collins P., Chalmers E., Alamelu J., Hay C., Liesner R., Makris M., et al. First-line immune tolerance induction for children with severe haemophilia A: A protocol from the UK Haemophilia Centre Doctors’ Organisation Inhibitor and Paediatric Working Parties. Haemophilia 2017; 23 (5): 654–9. DOI: 10.1111/hae.13264</mixed-citation><mixed-citation xml:lang="ru">Collins P., Chalmers E., Alamelu J., Hay C., Liesner R., Makris M., et al. First-line immune tolerance induction for children with severe haemophilia A: A protocol from the UK Haemophilia Centre Doctors’ Organisation Inhibitor and Paediatric Working Parties. Haemophilia 2017; 23 (5): 654–9. DOI: 10.1111/hae.13264</mixed-citation></citation-alternatives></ref><ref id="B9"><label>9.</label><citation-alternatives><mixed-citation xml:lang="en">9. Hart D. P., Alamelu J., Bhatnagar N., Biss T., Collins P. W., Hall G., et al. Immune tolerance induction in severe haemophilia A: A UKH-CDO inhibitor and paediatric working party consensus update. Haemophilia 2021; 27 (6): 932–7. DOI: 10.1111/hae.14381</mixed-citation><mixed-citation xml:lang="ru">Hart D. P., Alamelu J., Bhatnagar N., Biss T., Collins P. W., Hall G., et al. Immune tolerance induction in severe haemophilia A: A UKH-CDO inhibitor and paediatric working party consensus update. Haemophilia 2021; 27 (6): 932–7. DOI: 10.1111/hae.14381</mixed-citation></citation-alternatives></ref><ref id="B10"><label>10.</label><citation-alternatives><mixed-citation xml:lang="en">10. Ljung R., Auerswald G., Benson G., Dolan G., Duffy A., Hermans C., et al. Inhibitors in haemophilia A and B: Management of bleeds, inhibitor eradication and strategies for difficult-to-treat patients. Eur J Haematol 2019; 102 (2): 111–22. DOI: 10.1111/ejh.13193</mixed-citation><mixed-citation xml:lang="ru">Ljung R., Auerswald G., Benson G., Dolan G., Duffy A., Hermans C., et al. Inhibitors in haemophilia A and B: Management of bleeds, inhibitor eradication and strategies for difficult-to-treat patients. Eur J Haematol 2019; 102 (2): 111–22. DOI: 10.1111/ejh.13193</mixed-citation></citation-alternatives></ref><ref id="B11"><label>11.</label><citation-alternatives><mixed-citation xml:lang="en">11. Kreuz W., Escuriola Ettingshausen C., Vdovin V., Zozulya N., Plyushch О., Svirin P., et al. First prospective report on immune tolerance in poor risk haemophilia A inhibitor patients with a single factor VIII/von Willebrand factor concentrate in an observational immune tolerance induction study. Haemophilia 2016; 22 (1): 87–95. DOI: 10.1111/hae.12774</mixed-citation><mixed-citation xml:lang="ru">Kreuz W., Escuriola Ettingshausen C., Vdovin V., Zozulya N., Plyushch О., Svirin P., et al. First prospective report on immune tolerance in poor risk haemophilia A inhibitor patients with a single factor VIII/von Willebrand factor concentrate in an observational immune tolerance induction study. Haemophilia 2016; 22 (1): 87–95. DOI: 10.1111/hae.12774</mixed-citation></citation-alternatives></ref><ref id="B12"><label>12.</label><citation-alternatives><mixed-citation xml:lang="en">12. Oldenburg J., Jiménez-Yuste V., Peiró-Jordán R., Aledort L. M., Santagostino E. Primary and rescue immune tolerance induction in children and adults: A multicentre international study with a VWF-containing plasma-derived FVIII concentrate. Haemophilia 2014; 20 (1): 83–91. DOI: 10.1111/hae.12263</mixed-citation><mixed-citation xml:lang="ru">Oldenburg J., Jiménez-Yuste V., Peiró-Jordán R., Aledort L. M., Santagostino E. Primary and rescue immune tolerance induction in children and adults: A multicentre international study with a VWF-containing plasma-derived FVIII concentrate. Haemophilia 2014; 20 (1): 83–91. DOI: 10.1111/hae.12263</mixed-citation></citation-alternatives></ref><ref id="B13"><label>13.</label><citation-alternatives><mixed-citation xml:lang="en">13. Жарков П. А. Значительное снижение количества кровотечений у детей с ингибиторной формой гемофилии А в реальной клинической практике применения эмицизумаба П. А. Жарков [и др.] // Вопросы гематологии / онкологии и иммунопатологии в педиатрии. – 2022. – 21 (1): 66–71. DOI: 10.24287/1726-1708-2022-21-1-66-71</mixed-citation><mixed-citation xml:lang="ru">Жарков П. А. Значительное снижение количества кровотечений у детей с ингибиторной формой гемофилии А в реальной клинической практике применения эмицизумаба П. А. Жарков [и др.] // Вопросы гематологии / онкологии и иммунопатологии в педиатрии. – 2022. – 21 (1): 66–71. DOI: 10.24287/1726-1708-2022-21-1-66-71</mixed-citation></citation-alternatives></ref><ref id="B14"><label>14.</label><citation-alternatives><mixed-citation xml:lang="en">14. Saiyarsarai P., Robabpour Derakhshan A., Khedmati J., Eshghi P., Seyedifar M. A comparison between on-demand usage of rFVIIaь vs prophylaxis use of emicizumab in high titer inhibitory hemophilia A patients in Iran: A cost-utility analysis. Medicine (Baltimore) 2021; 100 (40): e27303. DOI: 10.1097/MD.0000000000027303</mixed-citation><mixed-citation xml:lang="ru">Saiyarsarai P., Robabpour Derakhshan A., Khedmati J., Eshghi P., Seyedifar M. A comparison between on-demand usage of rFVIIaь vs prophylaxis use of emicizumab in high titer inhibitory hemophilia A patients in Iran: A cost-utility analysis. Medicine (Baltimore) 2021; 100 (40): e27303. DOI: 10.1097/MD.0000000000027303</mixed-citation></citation-alternatives></ref><ref id="B15"><label>15.</label><citation-alternatives><mixed-citation xml:lang="en">15. Cortesi P. A., Castaman G., Trifirò G., Creazzola S. S., Improta G., Mazzaglia G., et al. Cost-Effectiveness and Budget Impact of Emicizumab Prophylaxis in Haemophilia A Patients with Inhibitors. Thromb Haemost 2020; 120 (2): 216–28. DOI: 10.1055/s-0039-3401822</mixed-citation><mixed-citation xml:lang="ru">Cortesi P. A., Castaman G., Trifirò G., Creazzola S. S., Improta G., Mazzaglia G., et al. Cost-Effectiveness and Budget Impact of Emicizumab Prophylaxis in Haemophilia A Patients with Inhibitors. Thromb Haemost 2020; 120 (2): 216–28. DOI: 10.1055/s-0039-3401822</mixed-citation></citation-alternatives></ref><ref id="B16"><label>16.</label><citation-alternatives><mixed-citation xml:lang="en">16. Жарков П. А. Современные возможности заместительной терапии и профилактики гемофилии А у детей / П. А. Жарков // Педиатрия. Журнал им. Г. Н. Сперанского. – 2021. –100 (2): 182–6. DOI: 10.24110/0031-403X-2021-100-2-182-187</mixed-citation><mixed-citation xml:lang="ru">Жарков П. А. Современные возможности заместительной терапии и профилактики гемофилии А у детей / П. А. Жарков // Педиатрия. Журнал им. Г. Н. Сперанского. – 2021. –100 (2): 182–6. DOI: 10.24110/0031-403X-2021-100-2-182-187</mixed-citation></citation-alternatives></ref><ref id="B17"><label>17.</label><citation-alternatives><mixed-citation xml:lang="en">17. Konkle B. A., Shapiro A. D., Quon D. V., Staber J. M., Kulkarni R., Ragni M. V., et al. BIVV001 Fusion Protein as Factor VIII Replacement Therapy for Hemophilia A. N Engl J Med 2020; 383 (11): 1018–27. DOI: 10.1056/nejmoa2002699</mixed-citation><mixed-citation xml:lang="ru">Konkle B. A., Shapiro A. D., Quon D. V., Staber J. M., Kulkarni R., Ragni M. V., et al. BIVV001 Fusion Protein as Factor VIII Replacement Therapy for Hemophilia A. N Engl J Med 2020; 383 (11): 1018–27. DOI: 10.1056/nejmoa2002699</mixed-citation></citation-alternatives></ref><ref id="B18"><label>18.</label><citation-alternatives><mixed-citation xml:lang="en">18. Pasi K. J., Laffan M., Rangarajan S., Robinson T. M., Mitchell N., Lester W., et al. Persistence of haemostatic response following gene therapy with valoctocogene roxaparvovec in severe haemophilia A. Haemophilia 2021; 27 (6): 947–56. DOI: 10.1111/hae.14391</mixed-citation><mixed-citation xml:lang="ru">Pasi K. J., Laffan M., Rangarajan S., Robinson T. M., Mitchell N., Lester W., et al. Persistence of haemostatic response following gene therapy with valoctocogene roxaparvovec in severe haemophilia A. Haemophilia 2021; 27 (6): 947–56. DOI: 10.1111/hae.14391</mixed-citation></citation-alternatives></ref></ref-list></back></article>
