bloodjourГематология и трансфузиологияRussian journal of hematology and transfusiology0234-57302411-3042ООО Издательский дом «Практика»10.35754/0234-5730-2024-69-2-217-225bloodjour-549Research ArticleОБЗОРЫREVIEWSТромбозы у больных наследственными коагулопатиямиThrombosis in patients with inherited coagulation factor disordersФлоринскийД. Б.FlorinskiyD. B.

Флоринский Дмитрий Борисович, кандидат медицинских наук, гематолог консультативного отделения стационара кратковременного лечения

117997, г. Москва

Dmitriy B. Florinskiy, Cand. Sci. (Med.), hematologist of Outpatient Consultative Unit, Daily hospital department

117997, Moscow

mitia94@yandex.ruhttps://orcid.org/0000-0003-4384-6754ЖарковП. А.ZharkovP. A.

Жарков Павел Александрович, доктор медицинских наук, гематолог консультативного отделения, заведующий лабораторией патологии гемостаза, профессор кафедры гематологии и клеточных технологий

117997, г. Москва

Pavel A. Zharkov,  Dr. Sci. (Med.), hematologist of Outpatient Consultative Unit, Head of Laboratory of Hemostasis Pathology, Professor of the Department of Hematology and Cell Technologies

117997, Moscow

pavel.zharkov@fccho-moscow.ruФГБУ «Национальный медицинский исследовательский центр детской гематологии, онкологии и иммунологии имени Дмитрия Рогачева» Министерства здравоохранения Российской ФедерацииРоссияDmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and ImmunologyRussian Federation202418082024692217225Copyright © Флоринский Д.Б., Жарков П.А., 20242024Флоринский Д.Б., Жарков П.А.Florinskiy D.B., Zharkov P.A.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.htjournal.ru/jour/article/view/549Введение

Введение.  Основным проявлением наследственных коагулопатий являются кровотечения, однако больные данными заболеваниями не защищены от тромботических событий.

Цель

Цель: оценить частоту и характер тромботических осложнений при различных коагулопатиях.

Основные сведения

Основные сведения. При некоторых коагулопатиях, как, например, при болезни Виллебранда, тромбозы встречаются редко, при других же, например при дисфибриногенемиях, тромбозы являются одним из ключевых проявлений. Для гемофилии А в последнее время наблюдается существенное расширение опций терапии. Применение некоторых новых препаратов уже на фазе клинических исследований было ассоциировано с тромботическими осложнениями.

Introduction

Introduction.  The main manifestation of hereditary coagulopathies is bleeding, but patients with these diseases are not protected from thrombotic complications.

Aim

Aim: to evaluate the frequency and nature of thrombotic complications in various bleeding disorders.

Main findings

Main findings.  In some bleeding disorders, such as von Willebrand disease, thromboses are extremely rare, while in others, such as dysfibrinogenemias, thrombosis is one of the key manifestations. For hemophilia A, there has recently been a significant expansion of treatment options. The use of some new drugs has already been associated with thrombotic complications in the clinical trial phase.

наследственные коагулопатиигемофилиятромбозредкие коагулопатииболезнь Виллебрандаrare bleeding disordershemophiliathrombosisvon Willebrand diseaseReferencesВоробьев А.И., Плющ О.П., Баркаган З.С. и др. Протокол ведения больных «гемофилия». Проблемы стандартизации в здравоохранении. 2006; 3: 18–74.Vorobiev A.I., Plush O.P., Barkagan Z.S., et al. Protocol of hemophilia patient treatment. Problemy standartizatii v Zdravoochranenii. 2006; 3: 18–74. (In Russian).Флоринский Д.Б., Жарков П.А. Редкие коагулопатии. Российский журнал детской гематологии и онкологии. 2020; 7(3): 54–63. DOI: 10.21682/2311-1267-2020-7-3-54-63.Florinskiy D.B., Zharkov P.A. Rare bleeding disorders. Rossiyskiy zurnal detskoy gematologii I onkologii. 2020; 7(3): 54–63. (In Russian). DOI: 10.21682/2311-1267-2020-7-3-54-63.Larsen J.B., Nielsen K.B.J., Poulsen L.H., et al. Arterial and Venous Thrombosis in Haemophilia Patients: Experiences from a Danish Haemophilia Centre. Acta Haematol. 2017; 138(2): 91–5. DOI: 10.1159/000477928.Larsen J.B., Nielsen K.B.J., Poulsen L.H., et al. Arterial and Venous Thrombosis in Haemophilia Patients: Experiences from a Danish Haemophilia Centre. Acta Haematol. 2017; 138(2): 91–5. DOI: 10.1159/000477928.Lutsey P.L., Zakai N.A. Epidemiology and prevention of venous thromboembolism. Nat Rev Cardiol. 2023; 20(4): 248–62. DOI: 10.1038/s41569-022-00787-6.Lutsey P.L., Zakai N.A. Epidemiology and prevention of venous thromboembolism. Nat Rev Cardiol. 2023; 20(4): 248–62. DOI: 10.1038/s41569-022-00787-6.Salari N., Morddarvanjoghi F., Abdolmaleki A., et al. The global prevalence of myocardial infarction: a systematic review and meta-analysis. BMC Cardiovasc Disord. 2023; 23(1): 206–15. DOI: 10.1186/s12872-023-03231-w.Salari N., Morddarvanjoghi F., Abdolmaleki A., et al. The global prevalence of myocardial infarction: a systematic review and meta-analysis. BMC Cardiovasc Disord. 2023; 23(1): 206–15. DOI: 10.1186/s12872-023-03231-w.https://npcpn.ru/doc/2020/rf-kr-insult.pdfhttps://npcpn.ru/doc/2020/rf-kr-insult.pdfKhan M.A., Hashim M.J., Mustafa H., et al. Global Epidemiology of Ischemic Heart Disease: Results from the Global Burden of Disease Study. Cureus. 2020; 12(7): e9349. DOI: 10.7759/cureus.9349.Khan M.A., Hashim M.J., Mustafa H., et al. Global Epidemiology of Ischemic Heart Disease: Results from the Global Burden of Disease Study. Cureus. 2020; 12(7): e9349. DOI: 10.7759/cureus.9349.Girolami A., Scandellari R., Zanon E., et al. Non-catheter associated venous thrombosis in hemophilia A and B. A critical review of all reported cases. J Thromb Thrombolysis. 2006; 21: 279–84 DOI: 10.1007/s11239-006-6556-7.Girolami A., Scandellari R., Zanon E., et al. Non-catheter associated venous thrombosis in hemophilia A and B. A critical review of all reported cases. J Thromb Thrombolysis. 2006; 21: 279–84 DOI: 10.1007/s11239-006-6556-7.https://clinicaltrials.gov/search?intr=Mim8https://clinicaltrials.gov/search?intr=Mim8Tagliaferri A., Rivolta G.F., Iorio A., et al. Mortality and causes of death in Italian persons with haemophilia, 1990–2007. Haemophilia. 2010; 16: 437–46. DOI: 10.1111/j.1365-2516.2009.02188.x.Tagliaferri A., Rivolta G.F., Iorio A., et al. Mortality and causes of death in Italian persons with haemophilia, 1990–2007. Haemophilia. 2010; 16: 437–46. DOI: 10.1111/j.1365-2516.2009.02188.x.Sood S.L., Cheng D., Ragni M., et al. A cross-sectional analysis of cardiovascular disease in the hemophilia population. Blood Adv. 2018; 2: 1325–33. DOI: 10.1182/bloodadvances.2018018226.Sood S.L., Cheng D., Ragni M., et al. A cross-sectional analysis of cardiovascular disease in the hemophilia population. Blood Adv. 2018; 2: 1325–33. DOI: 10.1182/bloodadvances.2018018226.Hermans C. Venous thromboembolic disease in patients with haemophilia. Thromb Res. 2012; 130: 30–2. DOI: 10.1016/j.thromres.2012.08.274.Hermans C. Venous thromboembolic disease in patients with haemophilia. Thromb Res. 2012; 130: 30–2. DOI: 10.1016/j.thromres.2012.08.274.Kashyap R., Sharma L.M., Gupta S., et al. Deep vein thrombosis in a patient with severe haemophilia A. Haemophilia. 2006; 12: 87–9. DOI: 10.1111/j.1365-2516.2006.01179.x.Kashyap R., Sharma L.M., Gupta S., et al. Deep vein thrombosis in a patient with severe haemophilia A. Haemophilia. 2006; 12: 87–9. DOI: 10.1111/j.1365-2516.2006.01179.x.Галстян Г.М., Полеводова О.А., Гавриш А.Ю. и др. Тромботические осложнения у больных гемофилией. Терапевтический архив. 2017: 89(7): 76–84. DOI: 10.17116/terarkh201789776-84.Galstyan G.M., Polevodova О.А., Gavrish A.Yu., et al. Thrombotic events in patients with hemophilia. Terapevticheskiy archiv. 2017: 89(7): 76–84. (In Russian). DOI: 10.17116/terarkh201789776-84.Buckner T.W., Leavitt A.D., Ragni M., et al. Prospective, multicenter study of postoperative deep-vein thrombosis in patients with haemophilia undergoing major orthopaedic surgery. Thromb Haemost. 2016; 116: 42–9. DOI: 10.1160/TH15-10-0802.Buckner T.W., Leavitt A.D., Ragni M., et al. Prospective, multicenter study of postoperative deep-vein thrombosis in patients with haemophilia undergoing major orthopaedic surgery. Thromb Haemost. 2016; 116: 42–9. DOI: 10.1160/TH15-10-0802.Perez Botero J., Spoon D.B., Patnaik M.S., et al. Incidence of symptomatic venous thromboembolism in patients with hemophilia undergoing joint replacement surgery: a retrospective study. Thromb Res. 2015; 135(1): 109–13. DOI: 10.1016/j.thromres.2014.11.010.Perez Botero J., Spoon D.B., Patnaik M.S., et al. Incidence of symptomatic venous thromboembolism in patients with hemophilia undergoing joint replacement surgery: a retrospective study. Thromb Res. 2015; 135(1): 109–13. DOI: 10.1016/j.thromres.2014.11.010.Raza S., Kale G., Kim D., et al. Thromboprophylaxis and Incidence of Venous Thromboembolism in Patients With Hemophilia A or B Who Underwent High-Risk Orthopedic Surgeries. Clin Appl Thromb Hemost. 2016; 22(2): 161–5. DOI: 10.1177/1076029614543139.Raza S., Kale G., Kim D., et al. Thromboprophylaxis and Incidence of Venous Thromboembolism in Patients With Hemophilia A or B Who Underwent High-Risk Orthopedic Surgeries. Clin Appl Thromb Hemost. 2016; 22(2): 161–5. DOI: 10.1177/1076029614543139.Krekeler S., Alesci S., Miesbach W. Untersuchung zum postoperativen Verlauf bei Patienten mit Hamophilie. Hamostaseologie. 2012; 32 (Suppl 1): S45–7.Krekeler S., Alesci S., Miesbach W. Untersuchung zum postoperativen Verlauf bei Patienten mit Hamophilie. Hamostaseologie. 2012; 32 (Suppl 1): S45–7.Шагдурова Б.В., Кудрявцева Л.М., Тенцова И.А. и др. Острый инфаркт миокарда у больного с тяжелой формой гемофилии А и терминальной стадией хронической почечной недостаточности Нефрология и диализ. 2003; 5(4): 405–9.Shagdurova B.V., Kudriavtseva L.M., Tentsova I.A., et al. Acute myocardial infarction in a patient with severe hemophilia A and terminal stage of chronic renal failure. Nephrologiya I Dialys. 2003; 5(4): 405–9. (In Russian).Callaghan M.U., Negrier C., Paz-Priel I., et al. Long-term outcomes with emicizumab prophylaxis for hemophilia A with or without FVIII inhibitors from the HAVEN 1–4 studies. Blood. 2021; 137(16): 2231–42. DOI: 10.1182/blood.2020009217.Callaghan M.U., Negrier C., Paz-Priel I., et al. Long-term outcomes with emicizumab prophylaxis for hemophilia A with or without FVIII inhibitors from the HAVEN 1–4 studies. Blood. 2021; 137(16): 2231–42. DOI: 10.1182/blood.2020009217.Koparkar S., Barlera S., Nissen F., et al. Evaluation of the safety of emicizumab prophylaxis in people with haemophilia A: an updated summary of thrombotic events and thrombotic microangiopathies, European Association for Haemophilia and Allied Disorders (EAHAD) Annual Meeting (7–10 February 2023) Manchester, UK. 2023.Koparkar S., Barlera S., Nissen F., et al. Evaluation of the safety of emicizumab prophylaxis in people with haemophilia A: an updated summary of thrombotic events and thrombotic microangiopathies, European Association for Haemophilia and Allied Disorders (EAHAD) Annual Meeting (7–10 February 2023) Manchester, UK. 2023.Young G., Lenting P.J., Croteau S.E., Nolan B., et al. Antithrombin lowering in hemophilia: a closer look at fitusiran. Res Pract Thromb Haemost. 2023; 7(4): 100179. DOI: 10.1016/j.rpth.2023.100179.Young G., Lenting P.J., Croteau S.E., Nolan B., et al. Antithrombin lowering in hemophilia: a closer look at fitusiran. Res Pract Thromb Haemost. 2023; 7(4): 100179. DOI: 10.1016/j.rpth.2023.100179.Shapiro A.D., Angchaisuksiri P., Astermark J., et al. Long-term efficacy and safety of subcutaneous concizumab prophylaxis in hemophilia A and hemophilia A/B with inhibitors. Blood Adv. 2022; 6(11): 3422–32. DOI: 10.1182/bloodadvances.2021006403.Shapiro A.D., Angchaisuksiri P., Astermark J., et al. Long-term efficacy and safety of subcutaneous concizumab prophylaxis in hemophilia A and hemophilia A/B with inhibitors. Blood Adv. 2022; 6(11): 3422–32. DOI: 10.1182/bloodadvances.2021006403.Mahlangu J.N. Progress in the Development of Anti-tissue Factor Pathway Inhibitors for Haemophilia Management. Front Med. 2021; 5(8): 670526. DOI:10.3389/fmed.2021.670526.Mahlangu J.N. Progress in the Development of Anti-tissue Factor Pathway Inhibitors for Haemophilia Management. Front Med. 2021; 5(8): 670526. DOI:10.3389/fmed.2021.670526.Shima M. Current status and future prospects of activated recombinant coagulation factor VIIa, NovoSeven®, in the treatment of haemophilia and rare bleeding disorders. Ann Hematol. 2023; 30: 33–45. DOI: 10.1007/s00277-023-05287-2.Shima M. Current status and future prospects of activated recombinant coagulation factor VIIa, NovoSeven®, in the treatment of haemophilia and rare bleeding disorders. Ann Hematol. 2023; 30: 33–45. DOI: 10.1007/s00277-023-05287-2.https://web.euhass.org/https://web.euhass.org/Weyand A.C., Flood V.H. Von Willebrand Disease: Current Status of Diagnosis and Management. Hematol Oncol Clin North Am. 2021; 35(6): 1085–101. DOI: 10.1016/j.hoc.2021.07.004.Weyand A.C., Flood V.H. Von Willebrand Disease: Current Status of Diagnosis and Management. Hematol Oncol Clin North Am. 2021; 35(6): 1085–101. DOI: 10.1016/j.hoc.2021.07.004.Girolami A., Tasinato V., Sambado L, et al. Venous thrombosis in von Willebrand disease as observed in one centre and as reported in the literature. Blood Coagul Fibrinolysis. 2015; 26(1): 54–8. DOI: 10.1097/MBC.0000000000000179.Girolami A., Tasinato V., Sambado L, et al. Venous thrombosis in von Willebrand disease as observed in one centre and as reported in the literature. Blood Coagul Fibrinolysis. 2015; 26(1): 54–8. DOI: 10.1097/MBC.0000000000000179.Sanders Y.V., Eikenboom J., de Wee E.M., et al. Reduced prevalence of arterial thrombosis in von Willebrand disease. J Thromb Haemost. 2013; 11(5): 845–54. DOI: 10.1111/jth.12194.Sanders Y.V., Eikenboom J., de Wee E.M., et al. Reduced prevalence of arterial thrombosis in von Willebrand disease. J Thromb Haemost. 2013; 11(5): 845–54. DOI: 10.1111/jth.12194.Галстян Г.М., Васильев С.А., Галузяк В.С., и др. Тромбоэмболия легочной артерии при болезни Виллебранда. Терапевтический архив. 2005; 12: 33–9.Galstyan G.М., Vasiliev S.A., Galuzyak V.S., et al. Thromboembolism of the pulmonary artery in Willebrand’s disease. Terapevticheskiy archiv. 2005; 12: 33–9. (In Russian).Ruiz-Saez A. Occurrence of thrombosis in rare bleeding disorders. Semin Thromb Hemost. 2013; 39(6): 684–92. DOI: 10.1055/s-0033-1353391.Ruiz-Saez A. Occurrence of thrombosis in rare bleeding disorders. Semin Thromb Hemost. 2013; 39(6): 684–92. DOI: 10.1055/s-0033-1353391.Marty S., Barro C., Chatelain B., et al. The paradoxical association between inherited factor VII deficiency and venous thrombosis. Haemophilia. 2008; 14(3): 564–70. DOI: 10.1111/j.1365-2516.2007.01647.x.Marty S., Barro C., Chatelain B., et al. The paradoxical association between inherited factor VII deficiency and venous thrombosis. Haemophilia. 2008; 14(3): 564–70. DOI: 10.1111/j.1365-2516.2007.01647.x.Mariani G., Napolitano M., Dolce A., et al. Adverse events in treatment of inherited factor VII deficiency: final analysis of the STER. ASH Annual Meeting Abstracts 2012; 120.Mariani G., Napolitano M., Dolce A., et al. Adverse events in treatment of inherited factor VII deficiency: final analysis of the STER. ASH Annual Meeting Abstracts 2012; 120.Girolami A., Ruzzon E., Tezza F., et al. Arterial and venous thrombosis in rare congenital bleeding disorders: a critical review. Haemophilia. 2006; 12(4): 345–51. DOI: 10.1111/j.1365-2516.2006.01299.x.Girolami A., Ruzzon E., Tezza F., et al. Arterial and venous thrombosis in rare congenital bleeding disorders: a critical review. Haemophilia. 2006; 12(4): 345–51. DOI: 10.1111/j.1365-2516.2006.01299.x.Salomon O., Steinberg D.M., Koren-Morag N., et al. Reduced incidence of ischemic stroke in patients with severe factor XI deficiency. Blood. 2008; 111(8): 4113–7. DOI: 10.1182/blood-2007-10-120139.Salomon O., Steinberg D.M., Koren-Morag N., et al. Reduced incidence of ischemic stroke in patients with severe factor XI deficiency. Blood. 2008; 111(8): 4113–7. DOI: 10.1182/blood-2007-10-120139.Salomon O., Steinberg D.M., Zucker M., et al. Patients with severe factor XI deficiency have a reduced incidence of deep-vein thrombosis. Thromb Haemost. 2011; 105(2): 269–73. DOI: 10.1160/TH10-05-0307.Salomon O., Steinberg D.M., Zucker M., et al. Patients with severe factor XI deficiency have a reduced incidence of deep-vein thrombosis. Thromb Haemost. 2011; 105(2): 269–73. DOI: 10.1160/TH10-05-0307.Lak M., Keihani M., Elahi F., Peyvandi F., et al. Bleeding and thrombosis in 55 patients with inherited afibrinogenaemia. Br J Haematol. 1999; 107(1): 204–6. DOI: 10.1046/j.1365-2141.1999.01681.x.Lak M., Keihani M., Elahi F., Peyvandi F., et al. Bleeding and thrombosis in 55 patients with inherited afibrinogenaemia. Br J Haematol. 1999; 107(1): 204–6. DOI: 10.1046/j.1365-2141.1999.01681.x.Simsek I., de Mazancourt P., Horellou M.H., et al. Afibrinogenemia resulting from homozygous nonsense mutation in A alpha chain gene associated with multiple thrombotic episodes. Blood Coagul Fibrinolysis. 2008; 19(3): 247–53. DOI:10.1097/MBC.0b013e3282f564fd.Simsek I., de Mazancourt P., Horellou M.H., et al. Afibrinogenemia resulting from homozygous nonsense mutation in A alpha chain gene associated with multiple thrombotic episodes. Blood Coagul Fibrinolysis. 2008; 19(3): 247–53. DOI:10.1097/MBC.0b013e3282f564fd.de Moerloose P., Neerman-Arbez M. Congenital fibrinogen disorders. Semin Thromb Hemost. 2009; 35(4): 356–66. DOI: 10.1055/s-0029-1225758.de Moerloose P., Neerman-Arbez M. Congenital fibrinogen disorders. Semin Thromb Hemost. 2009; 35(4): 356–66. DOI: 10.1055/s-0029-1225758.Haverkate F., Samama M. Familial dysfibrinogenemia and thrombophilia. Report on a study of the SSC Subcommittee on Fibrinogen. Thromb Haemost. 1995; 73(1): 151–61.Haverkate F., Samama M. Familial dysfibrinogenemia and thrombophilia. Report on a study of the SSC Subcommittee on Fibrinogen. Thromb Haemost. 1995; 73(1): 151–61.Hayes T. Dysfibrinogenemia and thrombosis. Arch Pathol Lab Med. 2002; 126(11): 1387–90.Hayes T. Dysfibrinogenemia and thrombosis. Arch Pathol Lab Med. 2002; 126(11): 1387–90.Shen Y.M., Trang V., Sarode R., et al. Fibrinogen Dusart presenting as recurrent thromboses in the hepatic portal system. Blood Coagul Fibrinolysis. 2014; 25(4): 392–4. DOI: 10.1097/MBC.0000000000000045.Shen Y.M., Trang V., Sarode R., et al. Fibrinogen Dusart presenting as recurrent thromboses in the hepatic portal system. Blood Coagul Fibrinolysis. 2014; 25(4): 392–4. DOI: 10.1097/MBC.0000000000000045.Casini A., Neerman-Arbez M., Ariens R.A., et al. Dysfibrinogenemia: from molecular anomalies to clinical manifestations and management. J Thromb Haemost. 2015; 13(6): 909–19. DOI: 10.1111/jth.12916.Casini A., Neerman-Arbez M., Ariens R.A., et al. Dysfibrinogenemia: from molecular anomalies to clinical manifestations and management. J Thromb Haemost. 2015; 13(6): 909–19. DOI: 10.1111/jth.12916.Sugo T., Endo H., Matsuda M., et al. A classification of the fibrin network structures formed from the hereditary dysfibrinogens. J Thromb Haemost. 2006; 4(8): 1738–46. DOI: 10.1111/j.1538-7836.2006.02043.x.Sugo T., Endo H., Matsuda M., et al. A classification of the fibrin network structures formed from the hereditary dysfibrinogens. J Thromb Haemost. 2006; 4(8): 1738–46. DOI: 10.1111/j.1538-7836.2006.02043.x.Casini A., Blondon M., Lebreton A., et al. Natural history of patients with congenital dysfibrinogenemia. Blood. 2015; 125(3): 553–61. DOI: 10.1182/blood-2014-06-582866.Casini A., Blondon M., Lebreton A., et al. Natural history of patients with congenital dysfibrinogenemia. Blood. 2015; 125(3): 553–61. DOI: 10.1182/blood-2014-06-582866.

The authors declare that there are no conflicts of interest present.