bloodjourГематология и трансфузиологияRussian journal of hematology and transfusiology0234-57302411-3042ООО Издательский дом «Практика»10.35754/0234-5730-2022-67-2-193-201bloodjour-362Research ArticleОРИГИНАЛЬНЫЕ СТАТЬИORIGINAL ARTICLESТромбозы у больных наследственной гипофибриногенемиейThrombosis in patients with hereditary fibrinogen deficiencyhttps://orcid.org/0000-0002-6991-7437ЯковлеваЕ. В.YakovlevaE. V.

Яковлева Елена Владимировна, кандидат медицинских наук, научный сотрудник, врач-гематолог отдела коагулопатий

125167, Москва

Elena V. Yakovleva, Cand. Sci. (Med.), Hematologist, Coagulopathies Department, National Medical Research Center for Hematology

125167, Moscow

hemophilia2012@mail.ruhttps://orcid.org/0000-0002-5669-3948СаломашкинаВ. В.SalomashkinaV. V.

Саломашкина Валентина Валерьевна, ведущий специалист лаборатории генной инженерии

125167, Москва

Valentina V. Salomashkina, Researcher, Laboratory of Genetic Engineering

125167, Moscow

prodoljenie-banketa@yandex.ruhttps://orcid.org/0000-0002-1890-4492СуринВ. Л.SurinV. L.

Сурин Вадим Леонидович, старший научный сотрудник лаборатории генной инженерии

125167, Москва

Vadim L. Surin, Senior Researcher, Laboratory of Genetic Engineering

125167, Moscow

vadsurin@mail.ruhttps://orcid.org/0000-0001-6043-6568СеливановаД. С.SelivanovaD. S.

Селиванова Дарья Сергеевна, научный сотрудник лаборатории генной инженерии

125167, Москва

Daria S. Selivanova, Researcher, Laboratory of Genetic Engineering

125167, Moscow

dahin@list.ruhttps://orcid.org/0000-0001-6251-331XЛавроваП. С.LavrovaP. S.

Лаврова Полина Сергеевна, врач клинико-диагностической лаборатории

125167, Москва

Polina S. Lavrova, Physician, Central Clinical Diagnostic Laboratory

125167, Moscow

lavrova.ps@gmail.comhttps://orcid.org/0000-0001-5235-2356ГоргидзеЛ. А.GorgidzeL. A.

Горгидзе Лана Анзоровна, кандидат биологических наук, старший научный сотрудник Экспресс-лаборатории

125167, Москва

Lana A. Gorgidze, Cand. Sci. (Biol.), Senior Researcher, Express Laboratory

125167, Moscow

lana380@mail.ruhttps://orcid.org/0000-0002-1903-2446СоболеваН. П.SobolevaN. P.

Соболева Наталья Павловна, врач клинико-диагностической лаборатории

125167, Москва

Natalia P. Soboleva, Physician, Central Clinical Diagnostic Laboratory

125167, Moscow

nsoboleva@list.ruhttps://orcid.org/0000-0001-7074-0926ЗозуляН. И.ZozulyaN. I.

Зозуля Надежда Ивановна, доктор медицинских наук, заведующая отделом коагулопатий

125167, Москва

Nadezhda I. Zozulya, Dr. Sci. (Med.), Head of Coagulopathies Department

125167, Moscow

zozulya.n@blood.ruФГБУ «Национальный медицинский исследовательский центр гематологии» Министерства здравоохранения Российской ФедерацииРоссияNational Medical Research Center for HematologyRussian Federation202206072022672193201Copyright © Яковлева Е.В., Саломашкина В.В., Сурин В.Л., Селиванова Д.С., Лаврова П.С., Горгидзе Л.А., Соболева Н.П., Зозуля Н.И., 20222022Яковлева Е.В., Саломашкина В.В., Сурин В.Л., Селиванова Д.С., Лаврова П.С., Горгидзе Л.А., Соболева Н.П., Зозуля Н.И.Yakovleva E.V., Salomashkina V.V., Surin V.L., Selivanova D.S., Lavrova P.S., Gorgidze L.A., Soboleva N.P., Zozulya N.I.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/362Введение

Введение. В большинстве случаев у больных наследственным дефицитом фибриногена клинические проявления представлены различными по интенсивности и локализации кровотечениями. Однако клиническая картина наследственного дефицита фибриногена может проявляться и тромбозами.

Цель — охарактеризовать выявленные мутации в генах фибриногена и проанализировать протромботические факторы у больных наследственной гипофибриногенемией и тромбозами.

Методы

Методы. Наблюдали 49 больных наследственной гипофибриногенемией, из них у 46 больных в анамнезе не было тромбозов, у 3 больных были тромбозы в анамнезе. Эти 3 больных составили группу исследования.

Результаты

Результаты. У всех 3 больных в гене гамма-цепи фибриногена (FGG) обнаружены гетерозиготные мутации, у одного из них — неописанная ранее делеция g.2653_2684+211del, p. (Asp167Glufs*2), удаляющая 32 концевых нуклеотида пятого экзона гена FGG и приводящая к образованию стоп-кодона на месте аминокислоты 168. У 2 других больных — миссенс-мутации c.1140T>A, p. (Cys365Ser) и c.1114A>T, p. (Asp356Val), которые могут определять тромбогенные свойства измененной белковой структуры фибриногена. Также выявлены иные протромботические факторы: генетические полиморфизмы низкого тромботического риска, операция, прием комбинированных оральных контрацептивов.

Заключение

Заключение. Наследственный дефицит фибриногена не играет протекторную роль в отношении развития тромбозов и может явиться причиной развития тромбозов, что связано с его многофункциональной ролью в системе гемостаза. Патогенез развития тромбозов у больных наследственной гипофибриногенемией мультифакторный и может быть связан с характеристиками основного белкового дефекта и сосуществованием наследственных и приобретенных факторов тромботического риска (оперативные вмешательства, прием комбинированных оральных контрацептивов и др.).

Introduction

Introduction. In most cases, in patients with hereditary fibrinogen deficiency, clinical manifestations are represented by bleeding of varying intensity and localization. However, the clinical picture of hereditary fibrinogen deficiency can also be represented by thrombosis.

Aim — to characterize the detected mutations in fibrinogen genes and to analyze prothrombotic factors in patients with hereditary hypofibrinogenemia and thrombosis.

Materials and methods

Materials and methods. Forty-nine patients with hereditary hypofibrinogenemia were observed, of which 46 patients had no history of thrombosis and 3 patients had a confirmed history of thrombosis. These 3 patients made up the study group.

Results

Results. Heterozygous mutations were found in all 3 patients in the fibrinogen gamma chain gene (FGG), one of them had a previously undescribed deletion g.2653_2684+211del, p.(Asp167Glufs*2), which removes 32 terminal nucleotides of the fifth exon of the FGG gene and leads to the formation of a stop codon in place of amino acid 168. In two other patients, there were missense mutations c.1140T>A, p.(Cys365Ser) and c.1114A>T, p.(Asp356Val), which can determine the thrombogenic properties of the altered protein structure of fibrinogen. Other prothrombotic factors were also identified: genetic polymorphisms of low thrombotic risk, surgery, taking combined oral contraceptives.

Conclusion

Conclusion. Hereditary fibrinogen deficiency does not play a protective role in relation to the development of thrombosis and may cause the development of thrombosis, which is associated with its multifunctional role in the hemostasis system. The pathogenesis of thrombosis in patients with hereditary hypofibrinogenemia is multifactorial and may be associated with the characteristics of the main protein defect and the coexistence of hereditary and acquired thrombotic risk factors (surgical interventions, taking combined oral contraceptives, etc.).

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