The relationship between extended D-dimer elevations and hereditary thrombophilia in COVID-19 patients

Yıl 2022, , 147 - 151, 26.09.2022

Kadir Serkan Yalçın , Hümeyra Yücetürk , Benan Kasapoğlu , Murat Kekilli

https://doi.org/10.47582/jompac.1140392

Cited By: 2

Öz

Aim: To compare the D-Dimer levels in patients with mild COVID-19 disease with and without hereditary thrombophilia.
Material and Method: Factor V Leiden (G1691A) mutation, methylene tetrahydrofolate gene mutation (C677T, A1298C), and PAI-1 (4G-5G) and FXIII (V34L) gene mutations were examined in all patients included in the study for various reasons such as recurrent miscarriage and venous embolism. Patients with any mutation were included in the hereditary thrombophilia group, while patients without mutations were included in the control group. D-dimer levels of the patients were also analyzed for the second time at least 25 days after admission. All included patients had received previously at least two doses of the BioNTech-Pfizer or CoronaVac vaccines.
Results: A total of 158 patients, 46 (29.1%) male and 112 (70.9%) female, were included in the study. The mean age of the patients included in the study was 39.08 ± 9.09 years. A total of 121 patients, 33 (27.3%) men and 88 (72.7) women, with hereditary thrombophilia were in the first group. A total of 37 patients, 13 (35.1%) male and 24 (64.9%) female, who did not have any mutations, were taken as the control group. Of the patients with hereditary thrombophilia, 47 (38.8%) had Factor V Leiden, 63 (52.1%) had MTHFR gene mutations, 32 (26.4%) had PAI-1 and 12 (9.9%) had FXIII gene mutations. When the D-dimer values of both groups were examined 20-35 days after admission to the hospital, the D-dimer level of the hereditary thrombophilia group was 667.26 ±354.11 while the D-dimer level of the control group was 369.76±173.45 (P=0.031). The D-dimer level of 23 patients in the hereditary thrombophilia group and 2 patients without thrombophilia were found to be above 1000ng/ml when they came for control.
Conclusion: It should be kept in mind that if there is prolonged or newly emerging D-dimer elevation in patients who had COVID-19 disease with mild-moderate symptoms, these patients may have hereditary thrombophilia.

Anahtar Kelimeler

COVID-19, Heredidary thrombophilia, D-dimer

COVID-19 hastalarında uzamış D-dimer yüksekliği ve herediter trombofili arasındaki ilişki

Öz

Amaç: Bu çalışmada herediter trombofili olan ve olmayan hafif Covid-19 hastalarında D-Dimer düzeylerinin karşılaştırılması amaçlanmıştır.
Gereç ve Yöntem: Tekrarlayan düşük ve venöz emboli gibi çeşitli nedenlerle daha önce Faktör V leiden (G1691A) mutasyonu, metilen tetrahidrofolat gen mutasyonu (C677T, A1298C), PAI-1 (4G-5G) ve FXIII (V34L) gen mutasyonları bakılmış olan hastalar çalışmaya alındı. Herhangi bir mutasyonu olan hastalar kalıtsal trombofili grubuna, mutasyonu olmayan hastalar kontrol grubuna alındı. Hastaların D-dimer düzeyleri başvurudan en az 25 gün sonra bir kez daha kontrol edilmişti. Çalışmaya dahil edilen tüm hastalar daha önce BioNTech-Pfizer veya CoronaVac aşılarından en az iki doz olmuştu.
Bulgular: Çalışmaya 46 (%29,1) erkek ve 112 (%70,9) kadın olmak üzere toplam 158 hasta dahil edildi. Hastaların yaş ortalaması 39,08±9,09 idi. Herediter trombofilisi olan 33 (%27,3) erkek, 88 (72,7) kadın toplam 121 hasta birinci grup olarak alındı. Herhangi bir mutasyonu olmayan 13 (%35,1) erkek ve 24 (%64,9) kadın toplam 37 hasta ise kotrol grubu olarak alındı. Kalıtsal trombofili hastalarının 47’sinde (%38,8) Faktör V Leiden, 63’ünde (%52,1) MTHFR gen mutasyonu, 32’sinde (%26,4) PAI-1 ve 12’sinde (%9,9) FXIII gen mutasyonu vardı. Hastaneye yatıştan 20-35 gün sonra her iki grubun D-dimer değerleri incelendiğinde, herediter trombofili grubunun D-dimer düzeyi 667,26 ±354,11, kontrol grubunun D-dimer düzeyi 369,76±3; 173,45 (P=0,031) olarak buluındu. Herediter trombofili grubundaki 23 hastanın ve trombofili olmayan 2 hastanın kontrole geldiklerinde D-dimer düzeyleri 1000ng/ml’nin üzerinde bulundu.
Sonuç: Hafif-orta semptomları olan COVID-19 hastalığında uzamış veya yeni ortaya çıkan D-dimer yüksekliği varsa bu hastalarda kalıtsal trombofili olabileceği akılda tutulmalıdır.

Anahtar Kelimeler

COVID-19, hereiditer trombofili, D-dimer

Kaynakça

• Kimball A, Hatfield KM, Arons M, et al. Asymptomatic and presymptomatic SARS-CoV-2 infections in residents of a long-term care skilled nursing facility - king county, Washington, MMWR Morb Mortal Wkly Rep 2020; 69: 377–81.
• World Health Organizatiron. WHO Coronavirus (COVID-19) Dashboard. Available online: https://COVID19.who.int/ (last acces 04/06/2022)
• Khan SS. The Central Role of PAI-1 in COVID-19: Thrombosis and beyond Am J Respir Cell Mol Biol 2021; 65: 238-40.
• Fraisse M, Logre E, Pajot O, Mentec H, Plantefeve G, Contou D. Thrombotic and hemorrhagic events in critically ill COVID-19 patients: a French monocenter retrospective study. Critical Care (London, England) 2020; 24: 275
• Al-Samkari H, Karp Leaf RS, Dzik WH, et al. COVID-19 and coagulation: bleeding and thrombotic manifestations of SARS-CoV-2 infection. Blood 2020; 136: 489–500.
• 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: 1421–4.
• Kashi M, Jacquin A, Dakhil B et al. Severe arterial thrombosis associated with COVID-19 infection. Thromb Res 2020; 192: 75–7.
• Labo N, Ohnuki H, Tosato G. Vasculopathy and coagulopathy associated with SARS-CoV-2 infection. Cells 2020; 9: 1583.
• Nauka PC, Oran E, Chekuri S. Deep venous thrombosis in a non-critically ill patient with novel COVID-19 infection. Thromb Res 2020; 192: 27–8.
• Gaffney PJ. Breakdown products of fibrin and fibrinogen: molecular mechanisms and clinical implications. J Clin Pathol 1980; 14: 10–7.
• Velavan TP, Meyer CG. Mild versus severe COVID-19: laboratory markers. Int J Infect Dis 2020; 95: 304–7.
• Lippi G, Plebani M. Laboratory abnormalities in patients with COVID-19 infection. Clin Chem Lab Med 2020; 58: 1131- 4.
• Iba T, Levy JH, Levi M, et al. Coagulopathy of coronavirus disease 2019. Crit Care Med 2020; 48: 1358–64.
• Huang C, Wang Y, Li X, Ren L, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet 2020; 395: 497–06.
• Rostami M, Mansouritorghabeh H. D-dimer level in COVID-19 infection: a systematic review. Expert Rev Hematol 2020 ;13: 1265-75.
• Harper PL, Theakston E, Ahmed J, Ockelford P. D-dimer concentration increases with age reducing the clinical value of the D-dimer assay in the elderly. Intern Med J 2007; 37: 607-13.
• Velavan TP, Meyer CG. Mild versus severe COVID-19: laboratory markers. Int J Infec Dis 2020; 95: 304–7.
• Oualim S, Abdeladim S, Ouarradi A, et al. Elevated levels of D-dimer in patients with COVID-19: prognosis value. Pan African Med J 2020; 35: 105.
• Zhang L, Yan X, Fan Q, et al. D-dimer levels on admission to predict in hospital mortality in patients with COVID-19. J Thromb Haemost 2020; 18: 1324-9.
• M, van der Poll T. Coagulation and sepsis. Thrombosis research 2017; 149: 38-44.
• Lapić I, Radić Antolic M, Horvat I, et al. Association of polymorphisms in genes encoding prothrombotic and cardiovascular risk factors with disease severity in COVID-19 patients: A pilot study. J Med Virol 2022; 94: 3669-75.
• Ponti G, Pastorino L, Manfredini M, et al. COVID-19 spreading across world correlates with C677T allele of the methylenetetrahydrofolate reductase gene prevalence. J Clin Lab Anal 2021; 35: 23798.
• Cao JI, Chen X, Jiang LI, et al. DJ‐1 suppresses ferroptosis through preserving the activity of S‐adenosyl homocysteine hydrolase. Nat Commun 2020; 11: 1251.