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Acil servis hastalarında COVID-19 enfeksiyonu ile Prothrombin G20210A (Faktör II) ve PAI-1 4G/5G polimorfizmlerinin ilişkisi

Yıl 2026, Cilt: 19 Sayı: 2 , 341 - 352 , 13.04.2026
https://doi.org/10.31362/patd.1778508
https://izlik.org/JA84YC55ZA

Öz

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.

Etik Beyan

Çalışma için Pamukkale Üniversitesi Girişimsel Olmayan Klinik Araştırmalar Etik Kurulu'ndan izin alınmıştır (İzin tarihi: 22.06.2021, dosya numarası: E-60116787-020-67183).

Destekleyen Kurum

Pamukkale Üniversitesi

Proje Numarası

2021TIPF020

Teşekkür

Destekleri için Pamukkale Üniversitesi Bilimsel Araştırma Projeleri Koordinasyon Birimi'ne teşekkür ederiz.

Kaynakça

  • 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

Association of Prothrombin G20210A (Factor II) and PAI-1 4G/5G polymorphisms with COVID-19 infection in emergency department patients

Yıl 2026, Cilt: 19 Sayı: 2 , 341 - 352 , 13.04.2026
https://doi.org/10.31362/patd.1778508
https://izlik.org/JA84YC55ZA

Öz

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.

Etik Beyan

Permission was obtained from Pamukkale University Non-Interventional Clinical Research Ethics Committee for the study (permission date: 22.06.2021, file number: E-60116787-020-67183).

Destekleyen Kurum

Pamukkale University

Proje Numarası

2021TIPF020

Teşekkür

The authors would like to thank the Pamukkale University Scientific Research Projects Coordination Unit for their support.

Kaynakça

  • 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
Toplam 19 adet kaynakça vardır.

Ayrıntılar

Birincil Dil İngilizce
Konular Acil Tıp
Bölüm Araştırma Makalesi
Yazarlar

Ayşegül Baştaş 0009-0009-0634-7658

Mert Özen 0000-0001-6653-3756

Murat Seyit 0000-0002-8324-9471

Yasemin Adalı 0000-0002-6314-4816

Atakan Yılmaz 0000-0002-9773-5681

Alten Oskay 0000-0003-4373-6280

Aylin Koseler 0000-0003-4832-0436

İbrahim Türkçüer 0000-0001-8342-4615

Proje Numarası 2021TIPF020
Gönderilme Tarihi 11 Eylül 2025
Kabul Tarihi 5 Kasım 2025
Yayımlanma Tarihi 13 Nisan 2026
DOI https://doi.org/10.31362/patd.1778508
IZ https://izlik.org/JA84YC55ZA
Yayımlandığı Sayı Yıl 2026 Cilt: 19 Sayı: 2

Kaynak Göster

AMA 1.Baştaş A, Özen M, Seyit M, vd. Association of Prothrombin G20210A (Factor II) and PAI-1 4G/5G polymorphisms with COVID-19 infection in emergency department patients. Pam Tıp Derg. 2026;19(2):341-352. doi:10.31362/patd.1778508
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