Вопросы гематологии/онкологии и иммунопатологии в педиатрии. 2021; 20: 52-59
Дисфункция эндотелия у пациентов с наследственным сфероцитозом и b-талассемией
https://doi.org/10.24287/1726-1708-2021-20-3-52-59Аннотация
Пациенты с наследственным сфероцитозом и b-талассемией характеризуются повышенным риском тромбоза по сравнению с общей популяцией. Развитие гиперкоагуляции может быть связано с эндотелиальной дисфункцией. Целью данного исследования является оценка состояния свертывания крови и эндотелия у детей с наследственным сфероцитозом и b-талассемией. Данное исследование одобрено независимым этическим комитетом и утверждено решением ученого совета НМИЦ ДГОИ им. Дмитрия Рогачева. Состояние системы гемостаза у 18 детей с наследственным сфероцитозом (10 мальчиков и 8 девочек от 1 до 13 лет) и 8 детей с b-талассемией (4 мальчика и 4 девочки от 3 до 8 лет) оценивали с использованием стандартных времен свертывания (активированное частичное тромбопластиновое время – АЧТВ, тромбиновое время – ТВ, протромбиновый индекс – ПИ), концентрации фибриногена и маркеров дисфункции эндотелия: концентраций эндотелина-1 и тромбомодулина. Пациенты с наследственным сфероцитозом были разделены на 2 подгруппы: во время гемолитического кризиса (n = 11) и вне гемолитического кризиса (n = 7). Пациентов с b-талассемией разделили на 3 подгруппы в зависимости от тяжести заболевания: большая, промежуточная и малая формы. Значения АЧТВ, ТВ и ПИ не различались между подгруппами. Мы обнаружили снижение концентрации фибриногена у пациентов с тяжелым течением заболевания: во время гемолитического кризиса при наследственном сфероцитозе (1,9 ± 0,3 мг/мл при референтном диапазоне 2–3,9 мг/мл) и при большой форме b-талассемии (1,8 ± 0,3 мг/мл при референтном диапазоне 2–3,9 мг/мл). Это может быть вызвано потреблением фибриногена при активном гемолизе. Содержание тромбомодулина было повышено у всех пациентов с наследственным сфероцитозом, но медианное значение было выше у пациентов с кризом (6665 пг/мл против 5976 пг/мл при референтном диапазоне 275–909 пг/мл). У пациентов с b-талассемией содержание тромбомодулина было значительно повышено при большой и промежуточной формах (6389 ± 537 пг/мл и 6804 ± 120 пг/мл соответственно) по сравнению с малой формой (2727 ± 213 пг/мл). Однако и при малой форме b-талассемии концентрация тромбомодулина все еще была выше нормального диапазона. Концентрация эндотелина-1 была повышена у 55% пациентов с наследственным сфероцитозом во время кризиса и 43% больных вне криза. В целом содержание эндотелина-1 было значительнее повышено у пациентов с большой и промежуточной формами b-талассемии (при малой форме соответствовало референтным значениям) по сравнению с пациентами с наследственным сфероцитозом даже во время криза (2,33 ± 2,89 фмоль/мл и 0,95 ± 0,35 фмоль/мл соответственно). Содержание тромбомодулина и эндотелина-1 выявляет дисфункцию эндотелия у детей с гемолизом, что может быть одной из причин прокоагулянтного состояния. Более резкие изменения наблюдаются при большей интенсивности гемолиза: у пациентов с наследственным сфероцитозом во время гемолитического кризиса и у больных с большой и промежуточной формами b-талассемии.
Список литературы
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Pediatric Hematology/Oncology and Immunopathology. 2021; 20: 52-59
Endothelial dysfunction in patients with hereditary spherocytosis and b-thalassemia
https://doi.org/10.24287/1726-1708-2021-20-3-52-59Abstract
Patients with hereditary spherocytosis and b-Thalassemia are characterized by the increased risk of thrombosis. The early manifestation of thrombotic complications can occur even in childhood especially after surgery. Hypercoagulability can be associated with endothelial dysfunction. The aim of this study was to investigate the hemostatic state and endothelial function in children with hereditary spherocytosis and b-thalassemia. The study was approved by the Independent Ethics Committee of the Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology. The hemostatic status of 18 children (10 boys and 8 girls from 1 to 13 years) with hereditary spherocytosis and of 8 children (4 boys and 4 girls from 3 to 8 years) with b-thalassemia was assessed using clotting times (activated partial thromboplastin time – APTT, thrombin time – TT, prothrombin time PT), fibrinogen levels and markers of endothelium dysfunction: endothelin-1 and thrombomodulin levels. Patients with hereditary spherocytosis were divided into 2 groups: during the hemolytic crisis (11 patients) and without the hemolytic crisis (7 patients). Patients with b-Thalassemia were divided into 3 groups: b-thalassemia major, b-thalassemia intermedia and b-thalassemia minor. APTT, TT and PT were not changed significantly between groups. We find the decreased fibrinogen levels in patients with severe condition: in hereditary spherocytosis patients during hemolytic crisis (1.9 ± 0.3 ng/ml with normal range 2–3.9 ng/ml) and in b-thalassemia major patients (1.8 ± 0.3 ng/ml with normal range 2–3.9 ng/ml). This could be caused by consumption of fibrinogen during acute hemolysis. The Thrombomodulin levels were increased in all hereditary spherocytosis patients, but median value was higher in group with hemolytic crisis (6665 pg/ml vs 5976 pg/ml with ormal value 275–909 pg/ml) indicating endothelium dysfunction and activation of blood clotting. In b-thalassemia patients Thrombomodulin levels were more elevated in b-thalassemia major and b-thalassemia intermedia (6389 ± 537 pg/ml и 6804 ± 120 pg/ml) compared to b-thalassemia minor (2727 ± 213 pg/ml) which is still higher than normal range. Endothelin-1 levels were elevated on 55% with hereditary spherocytosis patients during crisis vs 43% without. In general Endothelin-1 levels were more elevated in b-thalassemia patients (were normal in b-thalassemia minor) vs hereditary spherocytosis patients (2.33 ± 2.89 fmol/ml vs 0.95 ± 0.35 fmol/ml). Thrombomodulin and endothelin-1 levels revealed endothelium dysfunction in children with hemolysis. More dramatic changes observed in severe condition: in hereditary spherocytosis patients during hemolytic crisis and in b-thalassemia major and b-thalassemia intermedia patients.
References
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2. McGrew W., Avant G.R. Hereditary Spherocytosis and Portal Vein Thrombosis. J Clin Gastroenterol 1984; 6 (4): 381–2.
3. Ezov N., Levin-Harrus T., Mittelman M., Redlich M., Shabat S., Ward S.M., et al. A Chemically Induced Rat Model of Hemolysis with Disseminated Thrombosis. Cardiovasc Toxicol 2002; 2 (3); 181–93. DOI: 10.1007/s12012-002-0003-6
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13. Habib A., Kunzelmann C., Shamseddeen W., Zobairi F., Freyssinet J.-M., Taher A. Elevated Levels of Circulating Procoagulant Microparticles in Patients with Beta-Thalassemia Intermedia. Haematologica 2008; 93 (6): 941–2. DOI: 10.3324/haematol.12460
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