Retrospective Investigation of the Relationship between Hereditary Thrombophilia and COVID-19: A Single Center Experience
Öz
Objective: COVID-19 is a devastating pandemic caused by SARS-CoV-2, affecting all systems and showing its most important effect through thrombophilia. This study aimed to investigate the relationship between genotype and COVID-19 phenotype in patients whose hereditary thrombophilia susceptibility genes were examined.
Material and Methods: The sample of the study was selected from patients whose hereditary thrombophilia susceptibility genes were analyzed at the Medical Genetics Department of S.B. Dışkapı Yıldırım Beyazıt Training and Research Hospital between 2017 and 2021. The genotype-phenotype relationship was investigated in 66 patients whose genetic analysis was performed and diagnosed with COVID-19.
Results: Heterozygous prothrombin (FII)-G20210A in 2 patients, heterozygous Factor V Leiden (FVL)-G1691A in 11 patients, plasminogen activator inhibitor-1 (PAI) 4G/4G in 15 patients, PAI 4G/5G in 30 patients, 2 were homozygous F13, 15 were heterozygous F13, 23 were heterozygous Methylene tetrahydrofolate reductase (MTHFR) C677T (10 of them compound heterozygous), 10 were homozygous MTHFR C677T, 24 were heterozygous MTHFR A1298C (10 of them combined heterozygous), 10 of which were homozygous MTHFR A1298C genomic alterations were detected. A significant relationship was detected between FVL heterozygosity status and tachypnea and hypotension at diagnosis. Cases who were active smokers or had smoked in the past had significant lymphopenia compared to never-smokers. Additionally, troponin levels were found to be higher in active smokers compared to non-smokers.
Conclusion: In COVID-19 cases, investigating hereditary thrombophilia genes may help explain clinical findings. Data from this study have shown that in patients diagnosed with COVID-19, the clinical presentation of the disease is significantly affected by the state of FVL heterozygosity and smoking.
Anahtar Kelimeler
COVID-19 SARS-CoV-2 hereditary thrombophilia genetic testing smoking
Kaynakça
- 1. Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, et al. 2020. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet, 395(10223), 497-506.
- 2. Levi M, Thachil J, Iba T, Levy JH. 2020. Coagulation abnormalities and thrombosis in patients with COVID-19. Lancet Haematol, 7(6), e438-e440.
- 3. Oğuzlar FÇ, Tomruk Ö. 2021. Covid-19 Management In Emergency Service. Med J SDU, (ozelsayi-1), 189-196.
- 4. Alizad G, Ayatollahi AA, Shariati Samani A, Samadizadeh S, Aghcheli B, Rajabi A, et al. 2023. Hematological and Biochemical Laboratory Parameters in COVID-19 Patients: A Retrospective Modeling Study of Severity and Mortality Predictors. Biomed Res Int. 18,7753631. doi: 10.1155/2023/7753631. PMID: 38027038; PMCID: PMC10676280.
- 5. Gietl M, Burkert F, Hofer S, Gostner JM, Sonnweber T, Tancevski I, et al. 2024. Laboratory parameters related to disease severity and physical performance after reconvalescence of acute COVID-19 infection. Sci Rep. 14(1),10388. doi: 10.1038/s41598-024-57448-6. PMID: 38710760; PMCID: PMC11074335.
- 6. Jeraiby MA. 2024. Analysis of Laboratory Critical Values During COVID-19 Pandemic at Tertiary Hospital in Saudi Arabia. Int J Gen Med. 17,367-375. doi: 10.2147/IJGM.S449505. PMID: 38327817; PMCID: PMC10849053.
- 7. Montero S, Maguiña JL, Soto-Becerra P, Failoc-Rojas, Chira-Sosa J, Apolaya-Segura M, et al. 2024. Laboratory biomarkers associated with COVID-19 mortality among inpatients in a Peruvian referral hospital. Heliyon. 10(6):e27251. doi: 10.1016/j.heliyon.2024.e27251. PMID: 38500972; PMCID: PMC10945112.
- 8. Mahmood N, Riaz Z, Sattar A, Kiran M. 2023. Hematological findings in COVID-19 and their correlation with severity of Disease. Pak J Med Sci. 39(3):795-798. doi: 10.12669/pjms.39.3.6836. PMID: 37250575; PMCID: PMC10214815.
- 9. Bao C, Liu X, Zhang H, Li Y, Liu J. 2020. Coronavirus Disease 2019 (COVID-19) CT Findings: A Systematic Review and Meta-analysis. J Am Coll Radiol, 17(6), 701-709.
- 10. Montagnana M, Lippi G, Danese E. 2017. An Overview of Thrombophilia and Associated Laboratory Testing. Methods Mol Biol, 1646, 113-135
- 11. Pamukçu B. 2020. Inflammation and thrombosis in patients with COVID-19: A prothrombotic and inflammatory disease caused by SARS coronavirus-2. Anatol J Cardiol, 24(4), 224-234.
- 12. Altinisik J, Ates O, Ulutin T, Cengiz M, Buyru N. 2008. Factor V Leiden, prothrombin G20210A, and protein C mutation frequency in Turkish venous thrombosis patients. Clin Appl Thromb Hemost, 14(4), 415-20.
- 13. Kiraz A, Sezer O, Alemdar A, Canbek S, Duman N, Bisgin A, et al. 2023. Contribution of genotypes in Prothrombin and Factor V Leiden to COVID-19 and disease severity in patients at high risk for hereditary thrombophilia. J Med Virol, 95(2), e28457.
- 14. Cui S, Chen S, Li X, Liu S, Wang F. 2020. Prevalence of venous thromboembolism in patients with severe novel coronavirus pneumonia. J Thromb Haemost, 18(6), 1421-1424.
- 15. Kiraz A, Guzeldag S, Eren E, Goksu M, Bayram A. 2021. Investigation of the relationship between inherited thrombophilia and novel coronavirus pneumonia. Future Virol, fvl-2020-0395.
- 16. Losso JN. 2022. The Potential of Dietary Bioactive Compounds against SARS-CoV-2 and COVID-19-Induced Endothelial Dysfunction. Molecules, 27(5), 1623.
- 17. Nahum J, Morichau-Beauchant T, Daviaud F, Echegut P, Fichet J, Maillet JM, e al. 2020. Venous Thrombosis Among Critically Ill Patients With Coronavirus Disease 2019 (COVID-19). JAMA Netw Open, 3(5), e2010478.
- 18. Klok FA, Kruip MJHA, van der Meer NJM, Arbous MS, Gommers DAMPJ, Kant KM, et al. 2020. Incidence of thrombotic complications in critically ill ICU patients with COVID-19. Thromb Res, 191, 145-147.
- 19. Léonard-Lorant I, Delabranche X, Séverac F, Helms J, Pauzet C, Collange O, et al. 2020. Acute Pulmonary Embolism in Patients with COVID-19 at CT Angiography and Relationship to d-Dimer Levels. Radiology, 296(3), E189-E191.
- 20. Helms J, Tacquard C, Severac F, Leonard-Lorant I, Ohana M, Delabranche X, et al. 2020. CRICS TRIGGERSEP Group (Clinical Research in Intensive Care and Sepsis Trial Group for Global Evaluation and Research in Sepsis). High risk of thrombosis in patients with severe SARS-CoV-2 infection: a multicenter prospective cohort study. Intensive Care Med, 46(6), 1089-1098.
- 21. Middeldorp S, Coppens M, van Haaps TF, Foppen M, Vlaar AP, Müller MCA, et al. 2020. Incidence of venous thromboembolism in hospitalized patients with COVID-19. J Thromb Haemost, 18(8), 1995-2002.
- 22. Zhou F, Yu T, Du R, Fan G, Liu Y, Liu Z, et al. 2020. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet, 395(10229), 1054-1062.
- 23. Wichmann D, Sperhake JP, Lütgehetmann M, Steurer S, Edler C, Heinemann A, et al. 2020. Autopsy Findings and Venous Thromboembolism in Patients With COVID-19: A Prospective Cohort Study. Ann Intern Med, 173(4), 268-277.
- 24. Özbek N. 2009. Factor V 1691 G-A mutation distribution in a healthy Turkish population. Turk J Haematol, 26(1), 9-11.
- 25. Eroglu A, Sertkaya D, Akar N. 2012. The role of Factor V Leiden in adult patients with venous thromboembolism: a meta-analysis of published studies from Turkey. Clin Appl Thromb Hemost, 18(1), 40-4.
- 26. Rosendaal FR, Koster T, Vandenbroucke JP, Reitsma PH. 1995. High risk of thrombosis in patients homozygous for factor V Leiden (activated protein C resistance). Blood, 85(6), 1504-8.
- 27. Xie J, Prats-Uribe A, Feng Q, Wang Y, Gill D, Paredes R, et al. 2022. Clinical and Genetic Risk Factors for Acute Incident Venous Thromboembolism in Ambulatory Patients With COVID-19. JAMA Intern Med, 182(10), 1063-1070.
- 28. Lillicrap D. 2020. Disseminated intravascular coagulation in patients with 2019-nCoV pneumonia. J Thromb Haemost, 18(4), 786-787.
- 29. Çetin Kargin N. 2021. The effect of smoking on COVID-19-linked biomarkers in hospitalized patients with COVID-19. J Clin Lab Anal, 35(10), e23983.
- 30. Leung JM, Yang CX, Tam A, Shaipanich T, Hackett TL, Singhera GK, et al. 2020. ACE-2 expression in the small airway epithelia of smokers and COPD patients: implications for COVID-19. Eur Respir J, 55(5), 2000688.
- 31. Cai G, Bossé Y, Xiao F, Kheradmand F, Amos CI. 2020. Tobacco Smoking Increases the Lung Gene Expression of ACE2, the Receptor of SARS-CoV-2. Am J Respir Crit Care Med, 201(12),1557-1559.
- 32. Shevchuk O, Pak A, Palii S, Ivankiv Y, Kozak K, Korda M, et al. 2023. Blood ACE2 Protein Level Correlates with COVID-19 Severity. Int J Mol Sci. 24(18),13957.
- 33. Trofor AC, Robu Popa D, Melinte OE, Trofor L, Vicol C, Grosu-Creangă IA, et al. 2024. Looking at the Data on Smoking and Post-COVID-19 Syndrome-A Literature Review. J Pers Med. 14(1),97.
- 34. Vecchio J, Regan J, Jiang Y, Li R, Romain H, Yousuf F, et al. 2023. Viral and immunologic evaluation of smokers with severe COVID-19. Sci Rep. 13(1),17898. 35. Smith JC, Sausville EL, Girish V, Yuan ML, Vasudevan A, John KM, et al. 2020. Cigarette Smoke Exposure and Inflammatory Signaling Increase the Expression of the SARS-CoV-2 Receptor ACE2 in the Respiratory Tract. Dev Cell, 53(5), 514-529.
Öz
Amaç: COVID-19, SARS-CoV-2'un neden olduğu, tüm sistemleri etkileyen ve en önemli etkisini trombofili yoluyla göstermekte olan yıkıcı bir pandemi durumudur. Bu çalışma ile kalıtsal trombofili yatkınlık genleri incelenmiş olan hastalarda; genotip ve COVID-19 fenotip ilişkisinin araştırılması amaçlandı.
Gereç ve Yöntemler: Çalışmanın örneklemi, 2017-2021 yılları arasında, Dışkapı Yıldırım Beyazıt Eğitim ve Araştırma Hastanesi’nin Tıbbi Genetik Bölümü’nde kalıtsal trombofili yatkınlık genleri analiz edilmiş olan hastalardan seçilmiştir. Genetik analizi gerçekleşmiş ve COVID-19 COVID-19 teşhis edilen 66 hastanın genotip-fenotip ilişkisi araştırılmıştır.
Bulgular: Hastalardan 2’sinde heterozigot protrombin (FII)-G20210A, 11’inde heterozigot Faktör V Leiden (FVL)-G1691A, 15’inde plazminojen aktivatör inhibitörü-1 (PAI) 4G/4G, 30’unda PAI 4G/5G, 2’sinde homozigot F13, 15’inde heterozigot F13, 23’ünde heterozigot Metilen tetrahidrofolat redüktaz (MTHFR) C677T (bunların 10’u birleşik heterozigot), 10’u homozigot MTHFR C677T, 24’ünde heterozigot MTHFR A1298C (bunların 10’u birleşik heterozigot), 10’u homozigot MTHFR A1298C genomik değişimleri saptandı. FVL heterozigotluk durumu ile tanı anında takipne ve hipotansiyon arasında anlamlı bir ilişki saptandı. Aktif sigara kullanıcısı olan ve geçmişte kullanmış olan vakaların, hiç sigara kullanmamış olanlara kıyasla anlamlı düzeyde lenfopenisi vardı. Ayrıca aktif sigara kullanıcılarında, sigara kullanmayanlara göre troponin düzeyleri de daha yüksek olarak saptandı.
Sonuç: COVID-19 olgularında, kalıtsal trombofili genlerinin araştırılması farklı klinik bulguların açıklanmasında yardımcı olabilir. Bu çalışmadan elde edilen veriler, COVID-19 tanısı alan hastalarda, hastalığın klinik bulgularının, FVL heterozigotluk durumu ve sigara kullanımından önemli ölçüde etkilendiğini göstermiştir.
Anahtar Kelimeler
COVID-19 SARS-CoV-2 kalıtsal trombofili genetik test sigara kullanımı
Etik Beyan
Ankara Dışkapı Eğitim ve Araştırma Hastanesi'nin bağımsız Etik Kurulu’ndan, 31.05.2021 tarih ve 112/12 sayılı kararı ile onay alınmıştır.
Destekleyen Kurum
Bu araştırma, kamu, ticari veya kar amacı gütmeyen sektörlerdeki finansman kuruluşlarından herhangi bir finansal destek almamıştır.
Teşekkür
-
Kaynakça
- 1. Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, et al. 2020. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet, 395(10223), 497-506.
- 2. Levi M, Thachil J, Iba T, Levy JH. 2020. Coagulation abnormalities and thrombosis in patients with COVID-19. Lancet Haematol, 7(6), e438-e440.
- 3. Oğuzlar FÇ, Tomruk Ö. 2021. Covid-19 Management In Emergency Service. Med J SDU, (ozelsayi-1), 189-196.
- 4. Alizad G, Ayatollahi AA, Shariati Samani A, Samadizadeh S, Aghcheli B, Rajabi A, et al. 2023. Hematological and Biochemical Laboratory Parameters in COVID-19 Patients: A Retrospective Modeling Study of Severity and Mortality Predictors. Biomed Res Int. 18,7753631. doi: 10.1155/2023/7753631. PMID: 38027038; PMCID: PMC10676280.
- 5. Gietl M, Burkert F, Hofer S, Gostner JM, Sonnweber T, Tancevski I, et al. 2024. Laboratory parameters related to disease severity and physical performance after reconvalescence of acute COVID-19 infection. Sci Rep. 14(1),10388. doi: 10.1038/s41598-024-57448-6. PMID: 38710760; PMCID: PMC11074335.
- 6. Jeraiby MA. 2024. Analysis of Laboratory Critical Values During COVID-19 Pandemic at Tertiary Hospital in Saudi Arabia. Int J Gen Med. 17,367-375. doi: 10.2147/IJGM.S449505. PMID: 38327817; PMCID: PMC10849053.
- 7. Montero S, Maguiña JL, Soto-Becerra P, Failoc-Rojas, Chira-Sosa J, Apolaya-Segura M, et al. 2024. Laboratory biomarkers associated with COVID-19 mortality among inpatients in a Peruvian referral hospital. Heliyon. 10(6):e27251. doi: 10.1016/j.heliyon.2024.e27251. PMID: 38500972; PMCID: PMC10945112.
- 8. Mahmood N, Riaz Z, Sattar A, Kiran M. 2023. Hematological findings in COVID-19 and their correlation with severity of Disease. Pak J Med Sci. 39(3):795-798. doi: 10.12669/pjms.39.3.6836. PMID: 37250575; PMCID: PMC10214815.
- 9. Bao C, Liu X, Zhang H, Li Y, Liu J. 2020. Coronavirus Disease 2019 (COVID-19) CT Findings: A Systematic Review and Meta-analysis. J Am Coll Radiol, 17(6), 701-709.
- 10. Montagnana M, Lippi G, Danese E. 2017. An Overview of Thrombophilia and Associated Laboratory Testing. Methods Mol Biol, 1646, 113-135
- 11. Pamukçu B. 2020. Inflammation and thrombosis in patients with COVID-19: A prothrombotic and inflammatory disease caused by SARS coronavirus-2. Anatol J Cardiol, 24(4), 224-234.
- 12. Altinisik J, Ates O, Ulutin T, Cengiz M, Buyru N. 2008. Factor V Leiden, prothrombin G20210A, and protein C mutation frequency in Turkish venous thrombosis patients. Clin Appl Thromb Hemost, 14(4), 415-20.
- 13. Kiraz A, Sezer O, Alemdar A, Canbek S, Duman N, Bisgin A, et al. 2023. Contribution of genotypes in Prothrombin and Factor V Leiden to COVID-19 and disease severity in patients at high risk for hereditary thrombophilia. J Med Virol, 95(2), e28457.
- 14. Cui S, Chen S, Li X, Liu S, Wang F. 2020. Prevalence of venous thromboembolism in patients with severe novel coronavirus pneumonia. J Thromb Haemost, 18(6), 1421-1424.
- 15. Kiraz A, Guzeldag S, Eren E, Goksu M, Bayram A. 2021. Investigation of the relationship between inherited thrombophilia and novel coronavirus pneumonia. Future Virol, fvl-2020-0395.
- 16. Losso JN. 2022. The Potential of Dietary Bioactive Compounds against SARS-CoV-2 and COVID-19-Induced Endothelial Dysfunction. Molecules, 27(5), 1623.
- 17. Nahum J, Morichau-Beauchant T, Daviaud F, Echegut P, Fichet J, Maillet JM, e al. 2020. Venous Thrombosis Among Critically Ill Patients With Coronavirus Disease 2019 (COVID-19). JAMA Netw Open, 3(5), e2010478.
- 18. Klok FA, Kruip MJHA, van der Meer NJM, Arbous MS, Gommers DAMPJ, Kant KM, et al. 2020. Incidence of thrombotic complications in critically ill ICU patients with COVID-19. Thromb Res, 191, 145-147.
- 19. Léonard-Lorant I, Delabranche X, Séverac F, Helms J, Pauzet C, Collange O, et al. 2020. Acute Pulmonary Embolism in Patients with COVID-19 at CT Angiography and Relationship to d-Dimer Levels. Radiology, 296(3), E189-E191.
- 20. Helms J, Tacquard C, Severac F, Leonard-Lorant I, Ohana M, Delabranche X, et al. 2020. CRICS TRIGGERSEP Group (Clinical Research in Intensive Care and Sepsis Trial Group for Global Evaluation and Research in Sepsis). High risk of thrombosis in patients with severe SARS-CoV-2 infection: a multicenter prospective cohort study. Intensive Care Med, 46(6), 1089-1098.
- 21. Middeldorp S, Coppens M, van Haaps TF, Foppen M, Vlaar AP, Müller MCA, et al. 2020. Incidence of venous thromboembolism in hospitalized patients with COVID-19. J Thromb Haemost, 18(8), 1995-2002.
- 22. Zhou F, Yu T, Du R, Fan G, Liu Y, Liu Z, et al. 2020. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. Lancet, 395(10229), 1054-1062.
- 23. Wichmann D, Sperhake JP, Lütgehetmann M, Steurer S, Edler C, Heinemann A, et al. 2020. Autopsy Findings and Venous Thromboembolism in Patients With COVID-19: A Prospective Cohort Study. Ann Intern Med, 173(4), 268-277.
- 24. Özbek N. 2009. Factor V 1691 G-A mutation distribution in a healthy Turkish population. Turk J Haematol, 26(1), 9-11.
- 25. Eroglu A, Sertkaya D, Akar N. 2012. The role of Factor V Leiden in adult patients with venous thromboembolism: a meta-analysis of published studies from Turkey. Clin Appl Thromb Hemost, 18(1), 40-4.
- 26. Rosendaal FR, Koster T, Vandenbroucke JP, Reitsma PH. 1995. High risk of thrombosis in patients homozygous for factor V Leiden (activated protein C resistance). Blood, 85(6), 1504-8.
- 27. Xie J, Prats-Uribe A, Feng Q, Wang Y, Gill D, Paredes R, et al. 2022. Clinical and Genetic Risk Factors for Acute Incident Venous Thromboembolism in Ambulatory Patients With COVID-19. JAMA Intern Med, 182(10), 1063-1070.
- 28. Lillicrap D. 2020. Disseminated intravascular coagulation in patients with 2019-nCoV pneumonia. J Thromb Haemost, 18(4), 786-787.
- 29. Çetin Kargin N. 2021. The effect of smoking on COVID-19-linked biomarkers in hospitalized patients with COVID-19. J Clin Lab Anal, 35(10), e23983.
- 30. Leung JM, Yang CX, Tam A, Shaipanich T, Hackett TL, Singhera GK, et al. 2020. ACE-2 expression in the small airway epithelia of smokers and COPD patients: implications for COVID-19. Eur Respir J, 55(5), 2000688.
- 31. Cai G, Bossé Y, Xiao F, Kheradmand F, Amos CI. 2020. Tobacco Smoking Increases the Lung Gene Expression of ACE2, the Receptor of SARS-CoV-2. Am J Respir Crit Care Med, 201(12),1557-1559.
- 32. Shevchuk O, Pak A, Palii S, Ivankiv Y, Kozak K, Korda M, et al. 2023. Blood ACE2 Protein Level Correlates with COVID-19 Severity. Int J Mol Sci. 24(18),13957.
- 33. Trofor AC, Robu Popa D, Melinte OE, Trofor L, Vicol C, Grosu-Creangă IA, et al. 2024. Looking at the Data on Smoking and Post-COVID-19 Syndrome-A Literature Review. J Pers Med. 14(1),97.
- 34. Vecchio J, Regan J, Jiang Y, Li R, Romain H, Yousuf F, et al. 2023. Viral and immunologic evaluation of smokers with severe COVID-19. Sci Rep. 13(1),17898. 35. Smith JC, Sausville EL, Girish V, Yuan ML, Vasudevan A, John KM, et al. 2020. Cigarette Smoke Exposure and Inflammatory Signaling Increase the Expression of the SARS-CoV-2 Receptor ACE2 in the Respiratory Tract. Dev Cell, 53(5), 514-529.
Ayrıntılar
| Birincil Dil | Türkçe |
|---|---|
| Konular | Göğüs Hastalıkları, Tıbbi Genetik (Kanser Genetiği hariç) |
| Bölüm | Araştırma Makaleleri |
| Yazarlar | |
| Yayımlanma Tarihi | 25 Nisan 2025 |
| Gönderilme Tarihi | 6 Haziran 2024 |
| Kabul Tarihi | 31 Ekim 2024 |
| Yayımlandığı Sayı | Yıl 2025 Cilt: 16 Sayı: 1 |
