pam tıp derg Pamukkale Medical Journal 1308-0865 Pamukkale Üniversitesi 10.31362/patd.1778508 Emergency Medicine Acil Tıp Acil servis hastalarında COVID-19 enfeksiyonu ile Prothrombin G20210A (Faktör II) ve PAI-1 4G/5G polimorfizmlerinin ilişkisi Association of Prothrombin G20210A (Factor II) and PAI-1 4G/5G polymorphisms with COVID-19 infection in emergency department patients https://orcid.org/0009-0009-0634-7658 Baştaş Ayşegül PAMUKKALE ÜNİVERSİTESİ, TIP FAKÜLTESİ, DAHİLİ TIP BİLİMLERİ BÖLÜMÜ, ACİL TIP ANABİLİM DALI https://orcid.org/0000-0001-6653-3756 Özen Mert PAMUKKALE UNIVERSITY, FACULTY OF MEDICINE, DEPARTMENT OF INTERNAL MEDICINE, DEPARTMENT OF ACADEMIC EMERGENCY MEDICINE https://orcid.org/0000-0002-8324-9471 Seyit Murat PAMUKKALE UNIVERSITY, FACULTY OF MEDICINE, DEPARTMENT OF INTERNAL MEDICINE, DEPARTMENT OF ACADEMIC EMERGENCY MEDICINE https://orcid.org/0000-0002-6314-4816 Adalı Yasemin Pamukkale University https://orcid.org/0000-0002-9773-5681 Yılmaz Atakan PAMUKKALE UNIVERSITY, FACULTY OF MEDICINE, DEPARTMENT OF INTERNAL MEDICINE, DEPARTMENT OF ACADEMIC EMERGENCY MEDICINE https://orcid.org/0000-0003-4373-6280 Oskay Alten PAMUKKALE UNIVERSITY, FACULTY OF MEDICINE, DEPARTMENT OF INTERNAL MEDICINE, DEPARTMENT OF ACADEMIC EMERGENCY MEDICINE https://orcid.org/0000-0003-4832-0436 Koseler Aylin PAMUKKALE ÜNİVERSİTESİ, TIP FAKÜLTESİ, TEMEL TIP BİLİMLERİ BÖLÜMÜ, BİYOFİZİK ANABİLİM DALI https://orcid.org/0000-0001-8342-4615 Türkçüer İbrahim PAMUKKALE UNIVERSITY, FACULTY OF MEDICINE, DEPARTMENT OF INTERNAL MEDICINE, DEPARTMENT OF ACADEMIC EMERGENCY MEDICINE 04 13 2026 19 2 341 352 09 11 2025 11 05 2025 Copyright © 2008, Pamukkale Tıp Dergisi 2008 Pamukkale Tıp Dergisi

Amaç: Bu çalışma, Protrombin G20210A (Faktör II) ve PAI-1 4G/5G gen polimorfizmlerinin COVID-19 hastalığının şiddeti ve klinik sonuçları ile ilişkili olup olmadığını, Haziran-Aralık 2021 tarihleri arasında Pamukkale Üniversitesi Hastanesi Acil Servisine başvuran hastalarda araştırmayı amaçlamaktadır.Gereç ve yöntem: Prospektif, kesitsel ve gözlemsel nitelikteki bu çalışmada, PCR ile doğrulanmış 150 COVID-19 hastası ve 300 sağlıklı gönüllüde Protrombin G20210A ve PAI-1 4G/5G polimorfizmleri PCR ve DNA dizileme yöntemiyle genotiplendi. Laboratuvar parametreleri, hastalık şiddeti indeksleri, yoğun bakım ünitesine (YBÜ) yatış ve mortalite oranları değerlendirildi.Bulgular: Hastalarda Protrombin G20210A genotip dağılımı GA %54,7 ve GG %45,3; PAI-1 genotip dağılımı ise 4G/4G %77,3 ve 4G/5G %22,7 olarak saptandı. Protrombin G20210A varyantları arasında anlamlı fark bulunmadı; yalnızca GA grubunda lenfosit sayısı daha düşüktü (p=0,031). PAI-1 4G/5G grubunda monosit sayısı anlamlı olarak daha yüksek bulundu (p=0,012), ancak üre ve diğer biyokimyasal parametrelerde fark yoktu (p>0,05). Her iki genin heterozigot varyantlarını taşıyan hastalarda (çifte heterozigot, n=13) hemoglobin (p=0,010) ve lenfosit (p=0,012) düzeyleri düşük, monosit (p=0,001) ve ferritin (p=0,006) düzeyleri ise yüksek bulundu. Bu alt grupta ayrıca oksijen satürasyonu daha düşük (p=0,049), YBÜ yatışı (%46,2’ye karşı %15,3; p=0,005) ve mortalite oranı (%38,5’e karşı %9,5; p=0,002) anlamlı olarak daha yüksekti.Sonuç: Protrombin G20210A ve PAI-1 4G/5G polimorfizmleri, özellikle birlikte bulunduklarında, hematolojik ve inflamatuvar değişiklikler ile artmış YBÜ yatışı ve mortalite oranlarıyla ilişkilidir. Bu varyantlar risk sınıflandırması açısından potansiyel değer taşıyabilir ve daha büyük örneklemli çalışmalarda değerlendirilmelidir.

Purpose: This study aimed to investigate whether Prothrombin G20210A (Factor II) and PAI-1 4G/5G gene polymorphisms are associated with COVID-19 severity and clinical outcomes among patients admitted to the Emergency Department of Pamukkale University Hospital (Denizli, Türkiye) between June and December 2021.Materials and methods: In this prospective, cross-sectional, observational study, 150 PCR-confirmed COVID-19 patients and 300 healthy volunteers were genotyped for Prothrombin G20210A and PAI-1 4G/5G polymorphisms by PCR and DNA sequencing. Laboratory parameters, disease severity indices, intensive care unit (ICU) admission, and mortality were analyzed.Results: The genotype distribution among patients was GA 54.7% and GG 45.3% for Prothrombin G20210A, and 4G/4G 77.3% and 4G/5G 22.7% for PAI-1. There were no significant differences in Prothrombin G20210A variants except for lower lymphocyte counts in GA carriers (p=0.031). The PAI-1 4G/5G group showed a significantly higher monocyte count (p=0.012), while differences in urea and other biochemical parameters were not statistically significant (p>0.05). Patients carrying both PAI-1 and Prothrombin heterozygous variants (double heterozygotes, n=13) had lower hemoglobin (p=0.010) and lymphocyte counts (p=0.012), but higher monocyte (p=0.001) and ferritin levels (p=0.006). This subgroup also demonstrated lower oxygen saturation (p=0.049) and significantly higher intensive care unit admission (46.2% vs. 15.3%, p=0.005) and mortality (38.5% vs. 9.5%, p=0.002).Conclusion: Prothrombin G20210A and PAI-1 4G/5G polymorphisms particularly their coexistence were associated with hematologic and inflammatory alterations, as well as increased ICU admission and mortality rates. These variants may have potential value for risk stratification and should be evaluated in larger studies.

 COVID-19 Prothrombin G20210A PAI-1 thrombosis risk factors COVID-19 Protrombin G20210A PAI-1 tromboz risk faktörleri Pamukkale University 2021TIPF020 Tang N, Li D, Wang X, Sun Z. Abnormal coagulation parameters are associated with poor prognosis in patients with novel coronavirus pneumonia. J Thromb Haemost. 2020;18(4):844-847. doi:10.1111/jth.14768 Wang T, Chen R, Liu C, et al. Attention should be paid to venous thromboembolism prophylaxis in the management of COVID-19. Lancet Haematol. 2020;7(5):e362-e363. doi:10.1016/S2352-3026(20)30109-5 Driggin E, Madhavan MV, Bikdeli B, et al. Cardiovascular considerations for patients, health care workers, and health systems during the COVID-19 pandemic. J Am Coll Cardiol. 2020;75(18):2352-2371. doi:10.1016/j.jacc.2020.03.031 Menter T, Haslbauer JD, Nienhold R, et al. Postmortem examination of COVID-19 patients reveals diffuse alveolar damage with severe capillary congestion and variegated findings in lungs and other organs suggesting vascular dysfunction. Histopathology. 2020;77(2):198-209. doi:10.1111/his.14134 Wichmann D, Sperhake JP, Lütgehetmann M, et al. Autopsy findings and venous thromboembolism in patients with COVID-19: a prospective cohort study. Ann Intern Med. 2020;173(4):268-277. doi:10.7326/M20-2003 Lax SF, Skok K, Zechner P, et al. Pulmonary arterial thrombosis in COVID-19 with fatal outcome: results from a prospective, single-center, clinicopathologic case series. Ann Intern Med. 2020;173(5):350-361. doi:10.7326/M20-2566 Lodigiani C, Lapichino G, Carenzo L, et al. Venous and arterial thromboembolic complications in COVID-19 patients admitted to an academic hospital in Milan, Italy. Thromb Res. 2020;191:9-14. doi:10.1016/j.thromres.2020.04.024 Klok FA, Kruip MJHA, van der Meer NJM, et al. Incidence of thrombotic complications in critically ill ICU patients with COVID-19. Thromb Res. 2020;191:145-147. doi:10.1016/j.thromres.2020.04.013 Cui S, Chen S, Li X, Liu S, Wang F. Prevalence of venous thromboembolism in patients with severe novel coronavirus pneumonia. J Thromb Haemost. 2020;18(6):1421-1424. doi:10.1111/jth.14830 Helms J, Tacquard C, Severac F, et al. High risk of thrombosis in patients with severe SARS-CoV-2 infection: a multicenter prospective cohort study. Intensive Care Med. 2020;46(6):1089-1098. doi:10.1007/s00134-020-06062-x Sun W, Li Z, Shi Z, et al. Relationship between post-SARS osteonecrosis and PAI-1 4G/5G gene polymorphisms. Eur J Orthop Surg Traumatol. 2014;24(4):525-529. doi:10.1007/s00590-013-1223-0 Elkattawy S, Alyacoub R, Singh KS, Fichadiya H, Kessler W. Prothrombin G20210A gene mutation-induced recurrent deep vein thrombosis and pulmonary embolism: case report and literature review. J Investig Med High Impact Case Rep. 2022;10:23247096211058486. doi:10.1177/23247096211058486 Badulescu OV, Sirbu PD, Filip N, et al. Hereditary thrombophilia in the era of COVID-19. Healthcare (Basel). 2022;10(6):993. doi:10.3390/healthcare10060993 Yatsenko T, Rios R, Nogueira T, et al. The influence of 4G/5G polymorphism in the plasminogen-activator-inhibitor-1 promoter on COVID-19 severity and endothelial dysfunction. Front Immunol. 2024;15:1445294. doi:10.3389/fimmu.2024.1445294 Wang Z, Kong L, Luo G, et al. Clinical impact of the PAI-1 4G/5G polymorphism in Chinese patients with venous thromboembolism. Thromb J. 2022;20(1):68. doi:10.1186/s12959-022-00430-x Pan F, Ye T, Sun P, Gui S, Liang B, Li L, Zheng D, Wang J, Hesketh RL, Yang L, Zheng C. Time course of lung changes at chest CT during recovery from coronavirus disease 2019 (COVID-19). Radiology. 2020;295(3):715-721. doi:10.1148/radiol.2020200370 Zuo Y, Estes SK, Ali RA, et al. Prothrombotic autoantibodies in serum from patients hospitalized with COVID-19. Sci Transl Med. 2020;12(570):eabd3876. doi:10.1126/scitranslmed.abd3876 Whyte CS, Morrow GB, Mitchell JL, Chowdary P, Mutch NJ. Fibrinolytic abnormalities in acute respiratory distress syndrome (ARDS) and versatility of thrombolytic drugs to treat COVID-19. J Thromb Haemost. 2020;18(7):1548-1555. doi:10.1111/jth.14872 Ackermann M, Verleden SE, Kuehnel M, et al. Pulmonary vascular endothelialitis, thrombosis, and angiogenesis in COVID-19. N Engl J Med. 2020;383(2):120-128. doi:10.1056/NEJMoa2015432