de Vries Judith J, Visser Chantal, van Ommen Maureen, Rokx Casper, van Nood Els, van Gorp Eric C M, Goeijenbier Marco, van den Akker Johannes P C, Endeman Henrik, Rijken Dingeman C, Kruip Marieke J H A, Weggeman Miranda, Koopman Jaap, de Maat Moniek P M
Department of Hematology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, The Netherlands.
Fibriant BV, Leiden, The Netherlands.
TH Open. 2023 Jul 13;7(3):e217-e225. doi: 10.1055/a-2102-4521. eCollection 2023 Jul.
Fibrinogen variants as a result of alternative messenger RNA splicing or protein degradation can affect fibrin(ogen) functions. The levels of these variants might be altered during coronavirus disease 2019 (COVID-19), potentially affecting disease severity or the thrombosis risk. To investigate the levels of fibrinogen variants in plasma of patients with COVID-19. In this case-control study, we measured levels of functional fibrinogen using the Clauss assay. Enzyme-linked immunosorbent assays were used to measure antigen levels of total, intact (nondegraded Aα chain), extended Aα chain (α ), and γ' fibrinogen in healthy controls, patients with pneumococcal infection in the intensive care unit (ICU), ward patients with COVID-19, and ICU patients with COVID-19 (with and without thrombosis, two time points). Healthy controls and ward patients with COVID-19 ( = 10) showed similar fibrinogen (variant) levels. ICU patients with COVID-19 who later did ( = 19) or did not develop thrombosis ( = 18) and ICU patients with pneumococcal infection ( = 6) had higher absolute levels of functional, total, intact, and α fibrinogen than healthy controls ( = 7). The relative α fibrinogen levels were higher in ICU patients with COVID-19 than in healthy controls, while relative γ' fibrinogen levels were lower. After diagnosis of thrombosis, only the functional fibrinogen levels were higher in ICU patients with COVID-19 and thrombosis than in those without, while no differences were observed in the other fibrinogen variants. Our results show that severe COVID-19 is associated with increased levels of α fibrinogen and decreased relative levels of γ' fibrinogen, which may be a cause or consequence of severe disease, but this is not associated with the development of thrombosis.
由于信使核糖核酸可变剪接或蛋白质降解导致的纤维蛋白原变体可影响纤维蛋白（原）功能。在2019冠状病毒病（COVID-19）期间，这些变体的水平可能会发生改变，从而可能影响疾病严重程度或血栓形成风险。
为了研究COVID-19患者血浆中纤维蛋白原变体的水平。
在这项病例对照研究中，我们使用Clauss法测量功能性纤维蛋白原水平。采用酶联免疫吸附测定法测量健康对照者、重症监护病房（ICU）的肺炎球菌感染患者、COVID-19病房患者以及COVID-19 ICU患者（有或无血栓形成，两个时间点）的总纤维蛋白原、完整（未降解Aα链）、延长Aα链（α ）和γ'纤维蛋白原的抗原水平。
健康对照者和COVID-19病房患者（n = 10）的纤维蛋白原（变体）水平相似。后来发生（n = 19）或未发生血栓形成（n = 18）的COVID-19 ICU患者以及肺炎球菌感染的ICU患者（n = 6）的功能性、总、完整和α 纤维蛋白原的绝对水平高于健康对照者（n = 7）。COVID-19 ICU患者的相对α 纤维蛋白原水平高于健康对照者，而相对γ'纤维蛋白原水平较低。血栓形成诊断后，只有COVID-19合并血栓形成的ICU患者的功能性纤维蛋白原水平高于未合并血栓形成的患者，而其他纤维蛋白原变体未观察到差异。
我们的结果表明，重症COVID-19与α 纤维蛋白原水平升高和γ'纤维蛋白原相对水平降低有关，这可能是重症疾病的原因或后果，但这与血栓形成的发生无关。
