Hereditary thrombophilia as a possible risk factor for severe disease in COVID-19: a case series.

COVID-19 Forensic pathology Hereditary thrombophilia MTHFR PAI-1

Journal

Forensic science, medicine, and pathology
ISSN: 1556-2891
Titre abrégé: Forensic Sci Med Pathol
Pays: United States
ID NLM: 101236111

Informations de publication

Date de publication:
27 Sep 2024
Historique:
accepted: 14 08 2024
medline: 27 9 2024
pubmed: 27 9 2024
entrez: 27 9 2024
Statut: aheadofprint

Résumé

The risk factors that modulate one's susceptibility for severe COVID-19 have been well documented. Despite this, hypercoagulability remains an often overlooked risk factor for severe disease for COVID-19. Because COVID-19 infection is a risk factor for hypercoagulability, a reasonable presumption/hypothesis is that patients with hereditary thrombophilia would be at a higher risk of thrombotic complications associated with COVID-19 infection. This case report details two cases where previously unknown hereditary thrombophilias likely contributed to the mortality of COVID-19 patients. The first COVID-19 patient's cause of death was pulmonary thromboemboli from deep vein thrombosis due to heterozygous MTHFR C667T and heterozygous PAI-1 4G/5G mutations. The second COVID-19 patient's cause of death was an acute myocardial infarct due to a coronary artery thrombosis in the setting of heterozygous MTHFR A1298C and homozygous PAI-1 4G/5G mutations. In each case, COVID-19 infection was also considered contributory to death. The occurrence of these fatal thrombotic events in COVID-19 patients with hereditary thrombophilias raises questions as to whether this combination of thrombotic risk factors for hypercoagulability may have placed patients at a significant enough risk to experience these fatal thrombotic complications. Thus, while not sufficient alone to prove that SARS-CoV-2 patients with hereditary thrombophilias are at increased risk for thrombotic complications, these two cases indicate that further investigation is warranted into elucidating the relationship between thrombotic risk factors as it may identify an additional high-risk medical condition for COVID-19 and have important diagnostic and therapeutic ramifications.

Identifiants

pubmed: 39331315
doi: 10.1007/s12024-024-00879-4
pii: 10.1007/s12024-024-00879-4
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Informations de copyright

© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.

Références

Rashedi J, Mahdavi Poor B, Asgharzadeh V, et al. Risk factors for COVID-19. Infez Med. 2020;28(4):469–74.
pubmed: 33257620
People with certain medical conditions. In: COVID-19. Centers for Disease Control and Prevention. Published 2020. https://www.cdc.gov/coronavirus/2019-ncov/need-extra-precautions/people-with-medical-conditions.html . Accessed 5 Dec 2023.
‌Kichloo A, Dettloff K, Aljadah M, et al. COVID-19 and hypercoagulability: a review. Clin Appl Thromb Hemost. 2020. https://doi.org/10.1177/1076029620962853 .
doi: 10.1177/1076029620962853 pubmed: 33074732 pmcid: 7592310
Cheng NM, Chan YC, Cheng SW. COVID-19 related thrombosis: a mini-review. Phlebology. 2022;37(5):326–37. https://doi.org/10.1177/02683555211052170 .
doi: 10.1177/02683555211052170 pubmed: 35403487 pmcid: 9006089
Zuin M, Barco S, Giannakoulas G, et al. Risk of venous thromboembolic events after COVID-19 infection: a systematic review and meta-analysis. J Thromb Thrombolysis. 2023;55(3):490–8. https://doi.org/10.1007/s11239-022-02766-7 .
doi: 10.1007/s11239-022-02766-7 pubmed: 36652137 pmcid: 9845812
Massoud GP, Hazimeh DH, Amin G, et al. Risk of thromboembolic events in non-hospitalized COVID-19 patients: a systematic review. Eur J Pharmacol. 2023;941:175501. https://doi.org/10.1016/j.ejphar.2023.175501 .
doi: 10.1016/j.ejphar.2023.175501 pubmed: 36641102 pmcid: 9833853
Wheeler HB, Anderson FA Jr, Cardullo PA, Patwardhan NA, Jian-Ming L, Cutler BS. Suspected deep vein thrombosis. Management by impedance plethysmography. Arch Surg. 1982;117(9):1206–9. https://doi.org/10.1001/archsurg.1982.01380330064015 .
doi: 10.1001/archsurg.1982.01380330064015 pubmed: 6810844
Anderson FA Jr, Spencer FA. Risk factors for venous thromboembolism. Circulation. 2003;107(23 Suppl 1):I9–16. https://doi.org/10.1161/01.CIR.0000078469.07362.E6 .
doi: 10.1161/01.CIR.0000078469.07362.E6 pubmed: 12814980
Giannis D, Ziogas IA, Gianni P. Coagulation disorders in coronavirus infected patients: COVID-19, SARS-CoV-1, MERS-CoV and lessons from the past. J Clin Virol. 2020. https://doi.org/10.1016/j.jcv.2020.104362 .
doi: 10.1016/j.jcv.2020.104362 pubmed: 32305883 pmcid: 7195278
Han H, Yang L, Liu R, et al. Prominent changes in blood coagulation of patients with SARS-CoV-2 infection. Clin Chem Lab Med. 2020. https://doi.org/10.1515/cclm-2020-0188 .
doi: 10.1515/cclm-2020-0188 pubmed: 33001847
Abou-Ismail MY, Diamond A, Kapoor S, Arafah Y, Nayak L. The hypercoagulable state in COVID-19: incidence, pathophysiology, and management [published correction appears in Thromb Res. 2020]. Thromb Res. 2020. https://doi.org/10.1016/j.thromres.2020.06.029 .
doi: 10.1016/j.thromres.2020.06.029 pubmed: 33250201 pmcid: 7691845
Ali EW, Ibrahim IK. Multi-factorial mechanism behind COVID-19 related thrombosis. Med Arch. 2022;76(1):62–5. https://doi.org/10.5455/medarh.2022.76.62-65 .
doi: 10.5455/medarh.2022.76.62-65 pubmed: 35422572 pmcid: 8976895
Hanff TC, Mohareb AM, Giri J, Cohen JB, Chirinos JA. Thrombosis in COVID-19. Am J Hematol. 2020;95(12):1578–89. https://doi.org/10.1002/ajh.25982 .
doi: 10.1002/ajh.25982 pubmed: 32857878 pmcid: 7674272
Sarkar M, Madabhavi IV, Quy PN, Govindagoudar MB. COVID-19 and coagulopathy. Clin Respir J. 2021;15(12):1259–74. https://doi.org/10.1111/crj.13438 .
doi: 10.1111/crj.13438 pubmed: 34399021
Baglin T. Inherited and acquired risk factors for venous thromboembolism. Semin Respir Crit Care Med. 2012. https://doi.org/10.1055/s-0032-1311791 .
doi: 10.1055/s-0032-1311791 pubmed: 22648484
Zhang Q, Jin Y, Li X, et al. Plasminogen activator inhibitor-1 (PAI-1) 4G/5G promoter polymorphisms and risk of venous thromboembolism - a meta-analysis and systematic review. Vasa. 2020. https://doi.org/10.1024/0301-1526/a000839 .
doi: 10.1024/0301-1526/a000839 pubmed: 32933402
Nikolopoulos GK, Bagos PG, Tsangaris I, et al. The association between plasminogen activator inhibitor type 1 (PAI-1) levels, PAI-1 4G/5G polymorphism, and myocardial infarction: a mendelian randomization meta-analysis. Clin Chem Lab Med. 2014. https://doi.org/10.1515/cclm-2013-1124 .
doi: 10.1515/cclm-2013-1124 pubmed: 24695040
Liu Y, Cheng J, Guo X, et al. The roles of PAI-1 gene polymorphisms in atherosclerotic diseases: a systematic review and meta-analysis involving 149,908 subjects. Gene. 2018. https://doi.org/10.1016/j.gene.2018.06.040 .
doi: 10.1016/j.gene.2018.06.040 pubmed: 30599236 pmcid: 6320273
Raghubeer S, Matsha TE. Methylenetetrahydrofolate (MTHFR), the one-Carbon cycle, and Cardiovascular risks. Nutrients. 2021. https://doi.org/10.3390/nu13124562 .
doi: 10.3390/nu13124562 pubmed: 34960114 pmcid: 8703276
Dean L. Methylenetetrahydrofolate Reductase Deficiency. In: Pratt VM, Scott SA, Pirmohamed M, Esquivel B, Kattman BL, Malheiro AJ, eds. Medical Genetics Summaries. Bethesda (MD): National Center for Biotechnology Information (US); March 8, 2012.
Nappo F, De Rosa N, Marfella R, et al. Impairment of endothelial functions by acute hyperhomocysteinemia and reversal by antioxidant vitamins. JAMA. 1999. https://doi.org/10.1001/jama.281.22.2113 .
doi: 10.1001/jama.281.22.2113 pubmed: 10367822
Lijfering WM, Veeger NJ, Brouwer JL, van der Meer J. The risk of venous and arterial thrombosis in hyperhomocysteinemic subjects may be a result of elevated factor VIII levels. Haematologica. 2007. https://doi.org/10.3324/haematol.11611 .
doi: 10.3324/haematol.11611 pubmed: 18055997
Martí-Carvajal AJ, Solà I, Lathyris D, Dayer M. Homocysteine-lowering interventions for preventing cardiovascular events. Cochrane Database Syst Rev. 2017. https://doi.org/10.1002/14651858.CD006612.pub5 .
doi: 10.1002/14651858.CD006612.pub5 pubmed: 28816346 pmcid: 6483699
Ray JG. Meta-analysis of hyperhomocysteinemia as a risk factor for venous thromboembolic disease. Arch Intern Med. 1998. https://doi.org/10.1001/archinte.158.19.2101 .
doi: 10.1001/archinte.158.19.2101 pubmed: 9801176
Ospina-Romero M, Cannegieter SC, den Heijer M, Doggen CJM, Rosendaal FR, Lijfering WM. Hyperhomocysteinemia and risk of first venous thrombosis: the influence of (unmeasured) confounding factors. Am J Epidemiol. 2018. https://doi.org/10.1093/aje/kwy004 .
doi: 10.1093/aje/kwy004 pubmed: 29370361
Alizadeh S, Djafarian K, Moradi S, Shab-Bidar S. C667T and A1298C polymorphisms of methylenetetrahydrofolate reductase gene and susceptibility to myocardial infarction: a systematic review and meta-analysis. Int J Cardiol. 2016. https://doi.org/10.1016/j.ijcard.2016.04.181 .
doi: 10.1016/j.ijcard.2016.04.181 pubmed: 27179899
Gao M, Feng N, Zhang M, Ti X, Zuo X. Meta-analysis of the relationship between methylenetetrahydrofolate reductase C677T and A1298C polymorphism and venous thromboembolism in the caucasian and Asian. Biosci Rep. 2020. https://doi.org/10.1042/BSR20200860 .
doi: 10.1042/BSR20200860 pubmed: 33325526 pmcid: 7745063
Simsek E, Yesilyurt A, Pinarli F, Eyerci N, Ulus AT. Combined genetic mutations have remarkable effect on deep venous thrombosis and/or pulmonary embolism occurrence. Gene. 2014. https://doi.org/10.1016/j.gene.2014.02.046 .
doi: 10.1016/j.gene.2014.02.046 pubmed: 24334115
Levin BL, Varga E. MTHFR: addressing genetic counseling dilemmas using evidence-based literature. J Genet Couns. 2016. https://doi.org/10.1007/s10897-016-9956-7 .
doi: 10.1007/s10897-016-9956-7 pubmed: 27130656
Middeldorp S, Nieuwlaat R, Baumann Kreuziger L, et al. American Society of Hematology 2023 Guidelines for Management of venous thromboembolism: Thrombophilia Testing [published online ahead of print, 2023 May 17]. Blood Adv. 2023. https://doi.org/10.1182/bloodadvances.2023010177 .
doi: 10.1182/bloodadvances.2023010177 pubmed: 37195076 pmcid: 10709681
Badulescu OV, Sirbu PD, Filip N, et al. Hereditary Thrombophilia in the era of COVID-19. Healthc (Basel). 2022;10(6):993. https://doi.org/10.3390/healthcare10060993 . Published 2022 May 27.
doi: 10.3390/healthcare10060993
Kovac M, Mitic G, Milenkovic M, et al. Thrombosis risk assessment in patients with congenital thrombophilia during COVID – 19 infection. Thromb Res. 2022;218:151–6. https://doi.org/10.1016/j.thromres.2022.08.020 .
doi: 10.1016/j.thromres.2022.08.020 pubmed: 36054979 pmcid: 9392558
Elbadry MI, Tawfeek A, Abdellatif MG et al. Unusual pattern of thrombotic events in young adult non-critically ill patients with COVID-19 may result from an undiagnosed inherited and acquired form of thrombophilia [published correction appears in Br J Haematol. 2022;198(1):214. https://doi.org/10.1111/bjh.18301 . Br J Haematol. 2022;196(4):902–922. doi: https://doi.org/10.1111/bjh.17986 .

Auteurs

Jonathan Tse (J)

Western Michigan University Homer Stryker MD School of Medicine, 300 Portage St. Kalamazoo, Kalamazoo, MI, 49007, USA. Jonathan.tse@wmed.edu.

Julita Gongolli (J)

Western Michigan University Homer Stryker MD School of Medicine, 300 Portage St. Kalamazoo, Kalamazoo, MI, 49007, USA.

Joseph A Prahlow (JA)

Department of Pathology, St. Louis University School of Medicine, City of St. Louis, MO, USA.

Classifications MeSH