Primer Hastalarda Antiplatelet/Antikoagülan Kullanımı ve Prognozun Değerlendirilmesi COVID-19'lu Trombofili Hastaları
Year 2024,
Volume: 14 Issue: 4, 420 - 427, 31.12.2024
Alper Erkin
,
Ayşe Çelik Yılmaz
,
Cenk Sunu
Abstract
Objective: This study is aimed to investigate the relationship between inherited thrombophilia and COVID-19 symptoms and the outcomes of treatment strategies.
Materials and Methods: This descriptive and retrospective study included patients who were followed up for thrombophilia in a training and research hospital. Data from 121 patients who had COVID-19 infection and those who met the inclusion criteria were collected through retrospective examination of medical records and telephone interviews using a data collection form developed by the researchers. The data obtained from the study was evaluated using descriptive and comparative statistical methods.
Results: Among the patients diagnosed with COVID-19, 11.6% had severe clinical presentations requiring intensive care support. During COVID-19 infection, mostly no drug was preferred for treatment (51.2%), and the most preferred drug was acetylsalicylic acid (ASA) (33.1%). A total of 13 thromboembolic events occurred in 12 patients who were included in the study during and after COVID-19 infection. No thromboembolic events occurred in patients using warfarin or new-generation oral anticoagulants during COVID-19. There was no significant difference in thromboembolism complications among patients who did not use any medication, those who used ASA/clopidogrel, and those who used low molecular weight heparin during COVID-19 infection. The most common gene mutation in the study was plasminogen activator inhibitor-1 (PAI-1) mutation, and there was no statistically significant difference between PAI-1 gene mutation and new thrombotic events (p=0.988).
Conclusion: COVID-19 infection was found to cause bilateral lung involvement with diffuse microthrombi in patients with genetic thrombophilia. No new thromboembolic events occurred in patients with thrombophilia using warfarin or new-generation oral anticoagulants.
Ethical Statement
Çalışma için Sakarya Üniversitesi Etik Kurulundan etik onay alınmıştır (Tarih: 28.12.2020, sayı: 651).
References
- Gibbs DV, Shreenivas SS, & Hudock KM. Role of acute thrombosis in coronavirus disease 2019. Critical Care Clinics. 2022; 38(3): 491–504. doi: 10.1016/J.CCC.2022.03.003.
- Jayarangaiah A, Kariyanna PT, Chen X, Jayarangaiah A, Kumar A. COVID-19-associated coagulopathy: An exacerbated immunothrombosis response. Clinical and Applied Thrombosis/Hemostasis. 2020; 26. doi: 10.1177/1076029620943293.
- Foley JH, Conway EM. Cross talk pathways between coagulation and inflammation. Circulation Research. 2016; 118(9): 1392-1408. doi: 10.1161/CIRCRESAHA.116.306853.
- Bunch CM, Moore E, Moore HB, Neal MD, Thomas AV, Zackariya N, et al. Immuno-thrombotic complications of COVID-19: Implications for timing of surgery and anticoagulation. Frontiers in Surgery. 2022; 9: 889999. doi: 10.3389/FSURG.2022.889999.
- Khider L, Gendron N, Mauge L. Inherited Thrombophilia in the Era of Direct Oral Anticoagulants. International Journal of Molecular Sciences. 2021; 23(3), 1821. doi:10.3390/ijms23031821.
- Casini A, Undas A, Palla R, Thachil J, De Moerloose P. Diagnosis and classification of congenital fibrinogen disorders: Communication from the SSC of the ISTH. Journal of Thrombosis and Haemostasis. 2018; 16(9): 1887-1890. doi:10.1111/jth.14216.
- Martinelli I, De Stefano V, Mannucci PM. Inherited risk factors for venous thromboembolism. Nature Reviews Cardiology. 2014;11(3):140-156. doi: 10.1038/NRCARDIO.2013.211.
- McFadyen JD, Stevens H, Peter K. The emerging threat of (micro) thrombosis in COVID-19 and its therapeutic implications. Circulation Research. 2020;127(4):571-587. doi: 10.1161/CIRCRESAHA.120.317447.
- Sen U, Herrmann M, Herrmann W, Tyagi SC. Synergism between AT1 receptor and hyperhomocysteinemia during vascular remodeling. Clinical Chemistry and Laboratory Medicine. 2007; 45(12):1771-1776. doi: 10.1515/CCLM.2007.354.
- Yao D, Sun NL. Hyperhomocysteinemia accelerates collagen accumulation in the adventitia of balloon-injured rat carotid arteries via angiotensin II type 1 receptor. International Journal of Molecular Sciences. 2014; 15(11):19487-19498. doi: 10.3390/IJMS151119487.
- Zhang Q, Zeng X, Guo J, Wang X. Oxidant stress mechanism of homocysteine potentiating Con A-induced proliferation in murine splenic T lymphocytes. Cardiovascular research.2002;53(4):1035-1042. doi: 10.1016/S0008-6363(01)00541-7.
- Li T, Yu B, Liu Z, Li J, Ma M, Wang Y, et al. Homocysteine directly interacts and activates the angiotensin II type I receptor to aggravate vascular injury. Nature communications. 2018; 9(1), 11-18. doi: 10.1038/S41467-017-02401-7.
- Singh Y, Gupta G, Satija S, Negi P, Chellappan DK, Dua K. RAAS blockers in hypertension posing a higher risk toward the COVID‐19. Dermatologic therapy. 2020; 33(4). doi: 10.1111/DTH.13501.
- Fox SE, Akmatbekov A, Harbert JL, Li G, Brown JQ, Vander Heide RS. Pulmonary and cardiac pathology in African American patients with COVID-19: An autopsy series from New Orleans. The Lancet Respiratory Medicine. 2020; 8(7): 681-686. doi: 10.1016/S2213-2600(20)30243-5.
- Badulescu O, Sirbu P.D, Filip N, Bordeianu G, Cojocaru E, Budacu CC, Badescu C, Veliceasa B, Ciocoiu M. Hereditary Thrombophilia in the Era of COVID-19. Healthcare. 2022; 10(6): 993. doi: 10.3390/healthcare10060993.
- Abdullaev A, Fevraleva I, Odilov A, Volkov A, Babichenko I, Sudarikov A. Thrombotic events and the profile of hereditary thrombophilia factors in COVID-19 patients. HemaSphere. 2021; 5(S2): 641-641.
- Zhang Y, Guo R, Kim S.H, Shah H, Zhang S, Liang J.H., ... & Gewurz B.E. SARS-CoV-2 hijacks folate and one-carbon metabolism for viral replication. Nature communications.2021; 12(1):1676.
- Karst M, Hollenhors J, Achenbach J. Life-threatening course in coronavirus disease 2019 (COVID-19): Is there a link to methylenetetrahydrofolic acid reductase (MTHFR) polymorphism and hyperhomocysteinemia? Medical Hypotheses. 2020;144:110234. doi:10.1016/j.mehy.2020.110234.
- Cappadona C, Paraboschi EM, Ziliotto N, Bottaro S, Rimoldi V, Gerussi A, Azimonti A, Brenn D, Brunati A, Cameroni C, Campanaro G, Carloni F, Cavadini G, Ciravegna M, Composto A, Converso G, Corbella P, Dal Rì G, Di Giorgio SM, . . . Asselta R. MEDTEC Students against Coronavirus: Investigating the Role of Hemostatic Genes in the Predisposition to COVID-19 Severity. Journal of Personalized Medicine. 2021; 11(11):1166. doi: 0.3390/jpm11111166.
- Ponti G, Roli L, Oliva G, Manfredini M, Trenti T, Kaleci S, ... & Tomasi A. Homocysteine (Hcy) assessment to predict outcomes of hospitalized Covid-19 patients: A multicenter study on 313 Covid-19 patients. Clinical Chemistry and Laboratory Medicine (CCLM). 2021; 59(9): e354-e357.
- Hadid T, Kafri Z, Al-Katib A. Coagulation and anticoagulation in COVID-19. Blood Reviews. 2021;47:100761. doi: 10.1016/J.BLRE.2020.100761.
- Russo V, Di Maio M, Attena E, Silverio A, Scudiero F, Celentani D, et al. Clinical impact of pre-admission antithrombotic therapy in hospitalized patients with COVID-19: A multicenter observational study. Pharmacological Research. 2020;159:104965. doi: 10.1016/J.PHRS.2020.104965.
- Ciceri F, Beretta L, Scandroglio AM, Colombo S, Landoni G, Ruggeri A, Peccatori J, D'Angelo A, De Cobelli F, Rovere-Querini P, Tresoldi M, Dagna L, Zangrillo A. Microvascular COVID-19 lung vessels obstructive thromboinflammatory syndrome (MicroCLOTS): An atypical acute respiratory distress syndrome working hypothesis. Crit Care Resusc. 2020 Apr 15;22(2):95-97. doi: 10.51893/2020.2.pov2.
- Rivera‐Caravaca, J M, Núñez‐Gil I J, Vivas D, Viana‐Llamas MC, Uribarri A, Becerra‐Muñoz, VM. Clinical profile and prognosis in patients on oral anticoagulation before admission for COVID‐19. European Journal of Clinical Investigation. 2021;51(1):e13436. doi: 10.1111/ECI.13436.
- Tremblay D, Van Gerwen M, Alsen M, Thibaud S, Kessler A, Venugopal S, et al. Impact of anticoagulation prior to COVID-19 infection: A propensity score–matched cohort study. Blood, The Journal of the American Society of Hematology. 2020;136(1):144-147. doi: 10.1182/BLOOD.2020006941.
- Rossi R, Coppi F, Talarico M, Boriani G. Protective role of chronic treatment with direct oral anticoagulants in elderly patients affected by interstitial pneumonia in COVID-19 era. European journal of internal medicine. 2020;77:158-165. doi: 10.1016/J.EJIM.2020.06.006.
- Sivaloganathan H, Ladikou EE, Chevassut T. COVID‐19 mortality in patients on anticoagulants and antiplatelet agents. British journal of haematology. 2020;190(4):e192. doi: 10.1111/BJH.16968.
- Russo V, Bottino R, D’Andrea A, Silverio A, Di Maio M, Golino, P, et al. Chronic oral anticoagulation and clinical outcome in hospitalized COVID-19 patients. Cardiovascular Drugs and Therapy. 2022;36(4):705-712. doi:10.1007/S10557-021-07194-Y.
- Badulescu OV, Sirbu PD, Filip N, Bordeianu G, Cojocaru E, Budacu CC, Badescu M C, Veliceasa B, Ciocoiu M. Hereditary Thrombophilia in the Era of COVID-19. Healthcare. 2022; 10(6): 993. doi:10.3390/healthcare10060993.
- McFadyen JD, Stevens H, Peter K. The emerging threat of (micro) thrombosis in COVID-19 and its therapeutic implications. Circulation research. 2020;127(4):571-587.
- Barne GD, Burnett A, Allen A. Thromboembolism and anticoagulant therapy during the COVID-19 pandemic: Interim clinical guidance from the anticoagulation forum. J Thromb Thrombolysis. 2020; 50:72–81. doi:10.1007/s11239-020-02138-z.
Evaluation of Antiplatelet/Anticoagulant Use and Prognosis in Primary Thrombophilia Patients with COVID-19
Year 2024,
Volume: 14 Issue: 4, 420 - 427, 31.12.2024
Alper Erkin
,
Ayşe Çelik Yılmaz
,
Cenk Sunu
Abstract
Objective: This study is aimed to investigate the relationship between inherited thrombophilia and COVID-19 symptoms and the outcomes of treatment strategies.
Materials and Methods: This descriptive and retrospective study included patients who were followed up for thrombophilia in a training and research hospital. Data from 121 patients who had COVID-19 infection and those who met the inclusion criteria were collected through retrospective examination of medical records and telephone interviews using a data collection form developed by the researchers. The data obtained from the study was evaluated using descriptive and comparative statistical methods.
Results: Among the patients diagnosed with COVID-19, 11.6% had severe clinical presentations requiring intensive care support. During COVID-19 infection, mostly no drug was preferred for treatment (51.2%), and the most preferred drug was acetylsalicylic acid (ASA) (33.1%). A total of 13 thromboembolic events occurred in 12 patients who were included in the study during and after COVID-19 infection. No thromboembolic events occurred in patients using warfarin or new-generation oral anticoagulants during COVID-19. There was no significant difference in thromboembolism complications among patients who did not use any medication, those who used ASA/clopidogrel, and those who used low molecular weight heparin during COVID-19 infection. The most common gene mutation in the study was plasminogen activator inhibitor-1 (PAI-1) mutation, and there was no statistically significant difference between PAI-1 gene mutation and new thrombotic events (p=0.988).
Conclusion: COVID-19 infection was found to cause bilateral lung involvement with diffuse microthrombi in patients with genetic thrombophilia. No new thromboembolic events occurred in patients with thrombophilia using warfarin or new-generation oral anticoagulants.
References
- Gibbs DV, Shreenivas SS, & Hudock KM. Role of acute thrombosis in coronavirus disease 2019. Critical Care Clinics. 2022; 38(3): 491–504. doi: 10.1016/J.CCC.2022.03.003.
- Jayarangaiah A, Kariyanna PT, Chen X, Jayarangaiah A, Kumar A. COVID-19-associated coagulopathy: An exacerbated immunothrombosis response. Clinical and Applied Thrombosis/Hemostasis. 2020; 26. doi: 10.1177/1076029620943293.
- Foley JH, Conway EM. Cross talk pathways between coagulation and inflammation. Circulation Research. 2016; 118(9): 1392-1408. doi: 10.1161/CIRCRESAHA.116.306853.
- Bunch CM, Moore E, Moore HB, Neal MD, Thomas AV, Zackariya N, et al. Immuno-thrombotic complications of COVID-19: Implications for timing of surgery and anticoagulation. Frontiers in Surgery. 2022; 9: 889999. doi: 10.3389/FSURG.2022.889999.
- Khider L, Gendron N, Mauge L. Inherited Thrombophilia in the Era of Direct Oral Anticoagulants. International Journal of Molecular Sciences. 2021; 23(3), 1821. doi:10.3390/ijms23031821.
- Casini A, Undas A, Palla R, Thachil J, De Moerloose P. Diagnosis and classification of congenital fibrinogen disorders: Communication from the SSC of the ISTH. Journal of Thrombosis and Haemostasis. 2018; 16(9): 1887-1890. doi:10.1111/jth.14216.
- Martinelli I, De Stefano V, Mannucci PM. Inherited risk factors for venous thromboembolism. Nature Reviews Cardiology. 2014;11(3):140-156. doi: 10.1038/NRCARDIO.2013.211.
- McFadyen JD, Stevens H, Peter K. The emerging threat of (micro) thrombosis in COVID-19 and its therapeutic implications. Circulation Research. 2020;127(4):571-587. doi: 10.1161/CIRCRESAHA.120.317447.
- Sen U, Herrmann M, Herrmann W, Tyagi SC. Synergism between AT1 receptor and hyperhomocysteinemia during vascular remodeling. Clinical Chemistry and Laboratory Medicine. 2007; 45(12):1771-1776. doi: 10.1515/CCLM.2007.354.
- Yao D, Sun NL. Hyperhomocysteinemia accelerates collagen accumulation in the adventitia of balloon-injured rat carotid arteries via angiotensin II type 1 receptor. International Journal of Molecular Sciences. 2014; 15(11):19487-19498. doi: 10.3390/IJMS151119487.
- Zhang Q, Zeng X, Guo J, Wang X. Oxidant stress mechanism of homocysteine potentiating Con A-induced proliferation in murine splenic T lymphocytes. Cardiovascular research.2002;53(4):1035-1042. doi: 10.1016/S0008-6363(01)00541-7.
- Li T, Yu B, Liu Z, Li J, Ma M, Wang Y, et al. Homocysteine directly interacts and activates the angiotensin II type I receptor to aggravate vascular injury. Nature communications. 2018; 9(1), 11-18. doi: 10.1038/S41467-017-02401-7.
- Singh Y, Gupta G, Satija S, Negi P, Chellappan DK, Dua K. RAAS blockers in hypertension posing a higher risk toward the COVID‐19. Dermatologic therapy. 2020; 33(4). doi: 10.1111/DTH.13501.
- Fox SE, Akmatbekov A, Harbert JL, Li G, Brown JQ, Vander Heide RS. Pulmonary and cardiac pathology in African American patients with COVID-19: An autopsy series from New Orleans. The Lancet Respiratory Medicine. 2020; 8(7): 681-686. doi: 10.1016/S2213-2600(20)30243-5.
- Badulescu O, Sirbu P.D, Filip N, Bordeianu G, Cojocaru E, Budacu CC, Badescu C, Veliceasa B, Ciocoiu M. Hereditary Thrombophilia in the Era of COVID-19. Healthcare. 2022; 10(6): 993. doi: 10.3390/healthcare10060993.
- Abdullaev A, Fevraleva I, Odilov A, Volkov A, Babichenko I, Sudarikov A. Thrombotic events and the profile of hereditary thrombophilia factors in COVID-19 patients. HemaSphere. 2021; 5(S2): 641-641.
- Zhang Y, Guo R, Kim S.H, Shah H, Zhang S, Liang J.H., ... & Gewurz B.E. SARS-CoV-2 hijacks folate and one-carbon metabolism for viral replication. Nature communications.2021; 12(1):1676.
- Karst M, Hollenhors J, Achenbach J. Life-threatening course in coronavirus disease 2019 (COVID-19): Is there a link to methylenetetrahydrofolic acid reductase (MTHFR) polymorphism and hyperhomocysteinemia? Medical Hypotheses. 2020;144:110234. doi:10.1016/j.mehy.2020.110234.
- Cappadona C, Paraboschi EM, Ziliotto N, Bottaro S, Rimoldi V, Gerussi A, Azimonti A, Brenn D, Brunati A, Cameroni C, Campanaro G, Carloni F, Cavadini G, Ciravegna M, Composto A, Converso G, Corbella P, Dal Rì G, Di Giorgio SM, . . . Asselta R. MEDTEC Students against Coronavirus: Investigating the Role of Hemostatic Genes in the Predisposition to COVID-19 Severity. Journal of Personalized Medicine. 2021; 11(11):1166. doi: 0.3390/jpm11111166.
- Ponti G, Roli L, Oliva G, Manfredini M, Trenti T, Kaleci S, ... & Tomasi A. Homocysteine (Hcy) assessment to predict outcomes of hospitalized Covid-19 patients: A multicenter study on 313 Covid-19 patients. Clinical Chemistry and Laboratory Medicine (CCLM). 2021; 59(9): e354-e357.
- Hadid T, Kafri Z, Al-Katib A. Coagulation and anticoagulation in COVID-19. Blood Reviews. 2021;47:100761. doi: 10.1016/J.BLRE.2020.100761.
- Russo V, Di Maio M, Attena E, Silverio A, Scudiero F, Celentani D, et al. Clinical impact of pre-admission antithrombotic therapy in hospitalized patients with COVID-19: A multicenter observational study. Pharmacological Research. 2020;159:104965. doi: 10.1016/J.PHRS.2020.104965.
- Ciceri F, Beretta L, Scandroglio AM, Colombo S, Landoni G, Ruggeri A, Peccatori J, D'Angelo A, De Cobelli F, Rovere-Querini P, Tresoldi M, Dagna L, Zangrillo A. Microvascular COVID-19 lung vessels obstructive thromboinflammatory syndrome (MicroCLOTS): An atypical acute respiratory distress syndrome working hypothesis. Crit Care Resusc. 2020 Apr 15;22(2):95-97. doi: 10.51893/2020.2.pov2.
- Rivera‐Caravaca, J M, Núñez‐Gil I J, Vivas D, Viana‐Llamas MC, Uribarri A, Becerra‐Muñoz, VM. Clinical profile and prognosis in patients on oral anticoagulation before admission for COVID‐19. European Journal of Clinical Investigation. 2021;51(1):e13436. doi: 10.1111/ECI.13436.
- Tremblay D, Van Gerwen M, Alsen M, Thibaud S, Kessler A, Venugopal S, et al. Impact of anticoagulation prior to COVID-19 infection: A propensity score–matched cohort study. Blood, The Journal of the American Society of Hematology. 2020;136(1):144-147. doi: 10.1182/BLOOD.2020006941.
- Rossi R, Coppi F, Talarico M, Boriani G. Protective role of chronic treatment with direct oral anticoagulants in elderly patients affected by interstitial pneumonia in COVID-19 era. European journal of internal medicine. 2020;77:158-165. doi: 10.1016/J.EJIM.2020.06.006.
- Sivaloganathan H, Ladikou EE, Chevassut T. COVID‐19 mortality in patients on anticoagulants and antiplatelet agents. British journal of haematology. 2020;190(4):e192. doi: 10.1111/BJH.16968.
- Russo V, Bottino R, D’Andrea A, Silverio A, Di Maio M, Golino, P, et al. Chronic oral anticoagulation and clinical outcome in hospitalized COVID-19 patients. Cardiovascular Drugs and Therapy. 2022;36(4):705-712. doi:10.1007/S10557-021-07194-Y.
- Badulescu OV, Sirbu PD, Filip N, Bordeianu G, Cojocaru E, Budacu CC, Badescu M C, Veliceasa B, Ciocoiu M. Hereditary Thrombophilia in the Era of COVID-19. Healthcare. 2022; 10(6): 993. doi:10.3390/healthcare10060993.
- McFadyen JD, Stevens H, Peter K. The emerging threat of (micro) thrombosis in COVID-19 and its therapeutic implications. Circulation research. 2020;127(4):571-587.
- Barne GD, Burnett A, Allen A. Thromboembolism and anticoagulant therapy during the COVID-19 pandemic: Interim clinical guidance from the anticoagulation forum. J Thromb Thrombolysis. 2020; 50:72–81. doi:10.1007/s11239-020-02138-z.