Al- Anbar Medical Journal

COVID-19 Hypercoagulability Association with Serum Levels of Homocysteine and SCUBE-1

Document Type : Original articles

Authors

1 Department of Physiology, College of Medicine, Al Nahrain University, Baghdad, Iraq.

2 Medical Research Unit, College of Medicine, Al Nahrain University, Baghdad, Iraq.

Abstract

Background: Hypercoagulable state is a major complication of the coronavirus disease-2019 (COVID-19), with a possible result of debility and/or mortality. Homocysteine and SCUBE-1 are plasma biomarkers; their abnormal levels are relatable to coagulation as a cause or an effect.
Objectives: To investigate the association of homocysteine and SCUBE-1 with COVID-19–associated hypercoagulability.
Materials and Methods: This is a cross-sectional study with ninety adult COVID-19 patients with variable severity. Patients were classified according to D-dimer level at the time of hospital admission into two groups: with and without hypercoagulability. Serum was extracted from centrifuged blood (collected in gel tubes) and stored at -20 ºC. Serum levels of homocysteine and SCUBE-1 were measured utilizing Chemiluminescense Immunoassay and Enzyme-Linked Immunosorbent Assay, respectively, using commercially available kits.
Results: Thirty-eight patients (42.22%) out of the ninety had a hypercoagulable state, and the vast majority of patients with hypercoagulability (89.47%) had severe disease. The median (IQR) levels of homocysteine and SCUBE-1 in patients with hypercoagulability were 9.56 (8.75) µmol/L and 0.19 (0.11) ng/ml, respectively, which were higher than that of normal coagulable patients (8.15 [5.85] µmol/L and 0.16 [0.06] ng/ml, respectively) with highly significant differences (P-value = 0.044 and 0.01, respectively).
Conclusion: Homocysteine and SCUBE-1 serum levels are significantly associated with COVID-19 hypercoagulability and disease severity, and may be utilized as adjunct biomarkers for prediction/diagnosis of hypercoagulability in COVID-19 patients.

Keywords

Main Subjects

References
[1]      M. Kandeel, A. Ibrahim, M. Fayez, and M. Al‐Nazawi, “From SARS and MERS CoVs to SARS‐CoV‐2: Moving toward more biased codon usage in viral structural and nonstructural genes,” J. Med. Virol., vol. 92, no. 6, pp. 660–666, 2020.
[2]      H. Ghazzay, R. M. Al-Ani, M. A. Khalil, and A. F. Hammad, “Socio-clinical characteristics of COVID-19 disease in Anbar Governorate, Iraq,” J. Emerg. Med. Trauma Acute Care, vol. 2021, no. 1, p. 8, 2021.
[3]      N. M. Linton et al., “Incubation period and other epidemiological characteristics of 2019 novel coronavirus infections with right truncation: a statistical analysis of publicly available case data,” J. Clin. Med., vol. 9, no. 2, p. 538, 2020.
[4]      R. da Rosa Mesquita et al., “Clinical manifestations of COVID-19 in the general population: systematic review,” Wien. Klin. Wochenschr., vol. 133, no. 7–8, pp. 377–382, 2021.
[5]      I. A. Mahmood, K. A. Mahmood, and N. K. Alwan, “Predictive value of hematological and inflammatory markers for severity of COVID-19,” Biomedicine, vol. 42, no. 3, pp. 561–566, 2022.
[6]      C. M. Coopersmith et al., “The surviving sepsis campaign: research priorities for coronavirus disease 2019 in critical illness,” Crit. Care Med., vol. 49, no. 4, pp. 598–622, 2021.
[7]      W.-C. Park and J.-H. Chang, “Clinical implications of methylenetetrahydrofolate reductase mutations and plasma homocysteine levels in patients with thromboembolic occlusion,” Vasc. Spec. Int., vol. 30, no. 4, p. 113, 2014.
[8]      S. Turkmen et al., “The value of signal peptide‐CUB‐EGF domain‐containing protein 1 and oxidative stress parameters in the diagnosis of acute mesenteric ischemia,” Acad. Emerg. Med., vol. 20, no. 3, pp. 257–264, 2013.
[9]      M. A. M. Stals, F. H. J. Kaptein, L. J. M. Kroft, F. A. Klok, and M. V Huisman, “Challenges in the diagnostic approach of suspected pulmonary embolism in COVID-19 patients,” Postgrad. Med., vol. 133, no. sup1, pp. 36–41, 2021.
[10]    V. Ducros et al., “Should Plasma Homocysteine Be Used as a Biomarker of Venous Thromboembolism? A Case—Control Study,” Clin. Appl. Thromb., vol. 15, no. 5, pp. 517–522, 2009.
[11]    W.-J. Liao, M.-Y. Wu, C.-C. Peng, Y.-C. Tung, and R.-B. Yang, “Epidermal growth factor-like repeats of SCUBE1 derived from platelets are critical for thrombus formation,” Cardiovasc. Res., vol. 116, no. 1, pp. 193–201, 2020.
[12]    W. H. Organization, “Living guidance for clinical management of COVID-19: living guidance, 23 November 2021,” World Health Organization, 2021.
[13]    B. M. Henry et al., “Lactate dehydrogenase levels predict coronavirus disease 2019 (COVID-19) severity and mortality: A pooled analysis,” Am. J. Emerg. Med., vol. 38, no. 9, pp. 1722–1726, 2020.
[14]    Q. S. Al-Mayah, A. N. Umayra, and J. S. Hassan, “Association of TNF-α-308G/A Gene Polymorphism with Coronavirus Disease-19 Severity,” Med. J. Babylon, vol. 20, no. 1, p. 55, 2023.
[15]    Y. Lu et al., “A meta-analysis of the incidence of venous thromboembolic events and impact of anticoagulation on mortality in patients with COVID-19,” Int. J. Infect. Dis., vol. 100, pp. 34–41, 2020.
[16]    K. Toprak et al., “SCUBE1 is associated with thrombotic complications, disease severity, and in-hospital mortality in COVID-19 patients,” Thromb. Res., vol. 220, pp. 100–106, 2022.
[17]    B. A. Vučković, V. S. Čabarkapa, T. A. Ilić, I. R. Salatić, Z. S. Lozanov-Crvenković, and G. P. Mitić, “Clinical significance of determining plasma homocysteine: case-control study on arterial and venous thrombotic patients,” Croat. Med. J., vol. 54, no. 5, pp. 480–488, 2013.
[18]    A. W. Aday et al., “Homocysteine is associated with future venous thromboembolism in 2 prospective cohorts of women,” Arterioscler. Thromb. Vasc. Biol., vol. 41, no. 7, pp. 2215–2224, 2021.
[19]    X. Chen, W. Zhang, and J. Huang, “Homocysteine is potential serological marker for predicting the risk of deep venous thrombosis of the lower extremities in patients received operation of lower limb fracture,” Pteridines, vol. 32, no. 1, pp. 33–38, 2021.
[20]    Y. Yao et al., “Elevated homocysteine increases the risk of left atrial/left atrial appendage thrombus in non-valvular atrial fibrillation with low CHA2DS2-VASc score,” Ep Eur., vol. 20, no. 7, pp. 1093–1098, 2018.
[21]    L. Xiao et al., “The diagnostic potential of plasma SCUBE‐1 concentration for pulmonary embolism: A pilot study,” Clin. Respir. J., 2023.
[22]    F. Todua, M. Akhvlediani, E. Vorobiova, G. Tsivtsivadze, and A. Baramidze, “Homocysteine and D-dimer levels and multilayer computed tomography for diagnosing pulmonary artery thromboembolism,” Hospitals (Lond)., vol. 3, p. 5, 2017.
[23]    C.-H. Chuang et al., “Homocysteine and C-reactive protein as useful surrogate markers for evaluating CKD risk in adults,” Kidney Blood Press. Res., vol. 37, no. 4–5, pp. 402–413, 2013.
[24]    J. Perła-Kaján and H. Jakubowski, “COVID-19 and one-carbon metabolism,” Int. J. Mol. Sci., vol. 23, no. 8, p. 4181, 2022.
[25]    M. Abu-Farha et al., “Prognostic genetic markers for thrombosis in COVID-19 patients: a focused analysis on D-dimer, homocysteine and thromboembolism,” Front. Pharmacol., vol. 11, p. 587451, 2020.
[26]    A. Menteşe, G. Yilmaz, A. Sümer, M. Arslan, S. C. Karahan, and I. Köksal, “The diagnostic and prognostic significance of SCUBE1 levels in Crimean-Congo hemorrhagic fever,” Int. J. Infect. Dis., vol. 17, no. 11, pp. e1042–e1045, 2013.
[27]    O. Erol, H. Y. Ellidağ, M. K. Özel, A. U. Derbent, E. Eren, and N. Yılmaz, “Circulating SCUBE1 levels in women with polycystic ovary syndrome,” Turkish J. Obstet. Gynecol., vol. 15, no. 3, p. 152, 2018.
[28]    C.-F. Tu et al., “Localization and characterization of a novel secreted protein SCUBE1 in human platelets,” Cardiovasc. Res., vol. 71, no. 3, pp. 486–495, 2006.
[29]    C.-F. Tu et al., “Domain and functional analysis of a novel platelet-endothelial cell surface protein, SCUBE1,” J. Biol. Chem., vol. 283, no. 18, pp. 12478–12488, 2008.
[30]    G. Carpenè, D. Negrini, B. M. Henry, M. Montagnana, and G. Lippi, “Homocysteine in coronavirus disease (COVID-19): a systematic literature review,” Diagnosis, 2022.
 
Al- Anbar Medical Journal
Volume 19, Issue 2
December 2023
Page 116-122
Files
Share
Export Citation
Statistics