Ukr.Biochem.J. 2026; Volume 98, Issue 4, Jul-Aug, pp. 75-85

doi: https://doi.org/10.15407/ubj98.04.075

Markers of prothrombotic state of patients recovered after COVID-19

30.07.2026   Uncategorized

D. S. Korolova1*, O. O. Shevchuk2, O. P. Kostiuchenko1, T. M. Chernyshenko1,
K. P. Klymenko1, T. M. Platonova1, Ya. I. Ivankiv2, S. M. Palii2,
A. I. Voitovych2, V. O. Chernyshenko1, M. M. Korda2,
S. V. Komisarenko1, S. G. Vari3

1Palladin Institute of Biochemistry, National Academy of Sciences of Ukraine, Kyiv;
2Ivan Horbachevsky Ternopil Medical University, Ternopil, Ukraine;
3International Research and Innovation in Medicine Program, CSMC, Los-Angeles, CA, USA;
*e-mail: d.korolova@gmail.com

Received: 08 May 2026; Revised: 18 July 2026;
Accepted: 27 July 2026; Available on-line: 04 August 2026

Background. In recent period the attention of scientists and doctors was focused mainly on methods of COVID-19 treatment. However, clinical course of coronavirus disease strongly affects blood coagulation with the tendency for venous and arterial thrombosis, leading to long-term imbalance between coagulation and anticoagulation systems, which can cause serious danger for health of post-COVID-19 (PCD) patients. Objective. In our work we focused on the analysis of the molecular markers of hemostasis system activation in blood plasma of patients recovered after COVID-19. Methods. Blood plasma samples of 119 seropositive patients recovered from COVID-19 were analysed. The patients were divided into a high-risk group (HRG, n = 163) and a non-risk group (NRG, n = 28) according to WHO recommendations. Patients were examined in a recovery time scale of 1-30; 31-60 days and more than 2 months. Blood plasma samples of seronegative healthy volunteers were collected as the reference group (n = 19). The concentration of soluble fibrin (SF) and D-dimer was measured with sandwich ELISA, generation of activated protein C (PC) and prethrombin-1 (Pre-1)) level with assay using specific chromogenic substrates, and fibrinogen concentration with spectrophotometric method after initiation of coagulation by Ancistron-H. Results. Concentration of fibrinogen, SF and Pre-1 were increased in a blood plasma of patients of NRG and HRG groups in comparison to the reference group. Increasing of fibrinogen and Pre-1 concentrations correlated with COVID-19 stage. The fibrinogen and SF concentrations remained high more than 2 months after recovery in HRG group and elevated after 2 months after recovery in NRG group. D-dimer and protein C levels were elevated in 8% and 11% of PCD patients respectively. Conclusions. Long-term prethrombotic state was more expressed in HRG group of PCD patients. Monitoring of the main coagulation markers can indicate the risk of intravascular thrombus formation in PCD patients. SF, Pre-1 and elevated fibrinogen concentrations were selected as useful thrombosis markers in PCD patients.

Keywords: , , , , , ,

References:

  1. Komisarenko SV. Scientists’ pursuit for SARS-COV-2 coronavirus: strategies against pandemic. Ukr Biochem J. 2020;92(6):5-52. CrossRef
  2. Vari SG. COVID infection: disease mechanism, vascular dysfunction, immune responses, markers, multiorgan failure, treatments, and vaccination. Ukr Biochem J. 2020;92(3):6-21. CrossRef
  3. Asakura H, Ogawa H. COVID-19-associated coagulopathy and disseminated intravascular coagulation. Int J Hematol. 2021;113(1):45-57. PubMed, PubMedCentral, CrossRef
  4. Iba T, Levy JH, Connors JM, Warkentin TE, Thachil J, Levi M. The unique characteristics of COVID-19 coagulopathy. Crit Care. 2020;24(1):360. PubMed, PubMedCentral, CrossRef
  5. Franchini M, Marano G, Cruciani M, Mengoli C, Pati I, Masiello F, Veropalumbo E, Pupella S, Vaglio S, Liumbruno GM. COVID-19-associated coagulopathy. Diagnosis (Berl). 2020;7(4):357-363. PubMed, CrossRef
  6. Wang Z, Gao X, Miao H, Ma X, Ding R. Understanding COVID-19-associated coagulopathy: From PIC to SIC or DIC. J Intensive Med. 2021;1(1):35-41. PubMed, PubMedCentral, CrossRef
  7. Yu B, Li X, Chen J, Ouyang M, Zhang H, Zhao X, Tang L, Luo Q, Xu M, Yang L, Huang G, Liu X, Tang J. Evaluation of variation in D-dimer levels among COVID-19 and bacterial pneumonia: a retrospective analysis. J Thromb Thrombolysis. 2020;50(3):548-557. PubMed, PubMedCentral, CrossRef
  8. Al-Samkari H, Karp Leaf RS, Dzik WH, Carlson JCT, Fogerty AE, Waheed A, Goodarzi K, Bendapudi PK, Bornikova L, Gupta S, Leaf DE, Kuter DJ, Rosovsky RP. COVID-19 and coagulation: bleeding and thrombotic manifestations of SARS-CoV-2 infection. Blood. 2020;136(4):489-500. PubMed, PubMedCentral, CrossRef
  9. Calderon-Lopez MT, Garcia-Leon N, Gomez-Arevalillo S, Martin-Serrano P, Matilla-Garcia A. Coronavirus disease 2019 and coagulopathy: other prothrombotic coagulation factors. Blood Coagul Fibrinolysis. 2021;32(1):44-49. PubMed, CrossRef
  10. Eljilany I, Elzouki AN. D-Dimer, Fibrinogen, and IL-6 in COVID-19 Patients with Suspected Venous Thromboembolism: A Narrative Review. Vasc Health Risk Manag. 2020;16:455-462. PubMed, PubMedCentral, CrossRef
  11. Sridharan M, Ashrani AA, Chen D, Heikal NM, Marshall AL, Pruthi RK. Evaluation of Soluble Fibrin Monomer Complex in Patients with Sars-Cov-2 COVID Infection. Blood. 2020;136(Suppl 1): 27-28. CrossRef
  12. Al-Samkari H, Song F, Van Cott EM, Kuter DJ, Rosovsky R. Evaluation of the prothrombin fragment 1.2 in patients with coronavirus disease 2019 (COVID-19). Am J Hematol. 2020;95(12):1479-1485. PubMed, PubMedCentral, CrossRef
  13. Ranucci M, Sitzia C, Baryshnikova E, Di Dedda U, Cardani R, Martelli F, Corsi Romanelli M. Covid-19-Associated Coagulopathy: Biomarkers of Thrombin Generation and Fibrinolysis Leading the Outcome. J Clin Med. 2020;9(11):3487. PubMed, PubMedCentral, CrossRef
  14. Wool GD, Miller JL. The Impact of COVID-19 Disease on Platelets and Coagulation. Pathobiology. 2021;88(1):15-27. PubMed, PubMedCentral, CrossRef
  15. World Health Organization. Clinical management of severe acute respiratory infection when novel coronavirus (2019-nCoV) infection is suspected: interim guidance. January 28, 2020. (https://www.who.int/docs/default-source/coronaviruse/clinical-management-of-novel-cov.pdf)
  16. Solovyov DA, Platonova TN, Ugarova TP. Purification and characterization of ecamulin – a prothrombin activator from the venom of many-scaled viper ech is multisquamatus. Biochemystry. 1996;61(6):1094-1105.
  17. Chernyshenko VO, Chernyshenko TM, Korolova DS, Volynets GP, Kolesnikova IN, Platonova TM, Lugovskoy EV. Non-enzymatic activation of prothrombin induced by interaction with fibrin β26-42 region. Acta Biochim Pol. 2015;62(3):517-522. PubMed, CrossRef
  18. Platonova TM, Chernyshenko TM, Sokolovs’ka LI. Characteristics of D-domain-containing specific inhibitors of polymerization on the fibrin self-assembly process. Ukr Biokhim Zhurn. 2006;78(3):124-129. (In Ukrainian). PubMed
  19. Korolova DS, Chernyshenko TM, Gornytska OV, Chernyshenko OV, Platonova TN. Meizothrombin Preparation and Its Role in Fibrin Formation and Platelet Aggregation. Adv Biosci Biotechnol. 2014;5(7):588-595. CrossRef
  20. Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, Zhang L, Fan G, Xu J, Gu X, Cheng Z, Yu T, Xia J, Wei Y, Wu W, Xie X, Yin W, Li H, Liu M, Xiao Y, Gao H, Guo L, Xie J, Wang G, Jiang R, Gao Z, Jin Q, Wang J, Cao B. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. Lancet. 2020;395(10223):497-506. PubMed, PubMedCentral, CrossRef
  21. Roshan TM, Stein N, Jiang XY. Comparison of clot-based and chromogenic assay for the determination of protein c activity. Blood Coagul Fibrinolysis. 2019;30(4):156-160. PubMed, PubMedCentral, CrossRef
  22. Sokolovska AS, Chernyshenko TM, Ivanenko TI. Comparative characteristic of fibrinogen level determination methods in blood plasma. Exper Clin Phisiol Biochem. 2002; 3:82-86.
  23. Lugovskoi EV, Kolesnikova IN, Komisarenko SV. Usage of monoclonal antibodies for determination of localization of antigenic determinants and fibrin polymerization sites within fibrinogen and fibrin molecules and their application in test-systems for diagnostics and the threat of thrombus formation. Biotechnol Acta. 2013;6(4):33-42. CrossRef
  24. Lugovska NE, Kolesnikova IM, Stohnii YeM, Chernyshenko VO, Rebriev AV, Kostiuchenko OP, Gogolinska GK, Dziubliuk NA, Varbanets LD, Platonova TM, Komisarenko SV. Novel monoclonal antibody to fibrin(ogen) αC-region for detection of the earliest forms of soluble fibrin. Ukr Biochem J. 2020;92(3):58-70. CrossRef
  25. Lugovskoy EV, Gritsenko PG, Kolesnikova IN, Lugovskaya NE, Komisarenko SV. A neoantigenic determinant in coiled coil region of human fibrin beta-chain. Thromb Res. 2009;123(5):765-770. PubMed, CrossRef
  26. Lugovskoy EV, Gritsenko PG, Kolesnikova IN, Zolotarova EN, Chernishov VI, Nieuwenhuizen W, Komisarenko SV. Two monoclonal antibodies to D-dimer-specific inhibitors of fibrin polymerization. Thromb Res. 2004;113(3-4):251-259. PubMed, CrossRef
  27. Korolova D, Chernyshenko V, Platonova T, Chernyshenko T, Lugovskoy E. Detection of Prethrombin 1 in human blood plasma. Int Blood Res Reviews. 2016;5(2):1-7. CrossRef
  28. Budzynski AZ. Chromogenic Substrates in Coagulation and Fibrinolytic Assays. Lab Med. 2001;32(7):365-368. CrossRef
  29. Davalos D, Akassoglou K. Fibrinogen as a key regulator of inflammation in disease. Semin Immunopathol. 2012;34(1):43-62. PubMed, CrossRef
  30. Hosaka A, Miyata T, Aramoto H, Shigematsu H, Nakazawa T, Okamoto H, Shigematsu K, Nagawa H. Clinical implication of plasma level of soluble fibrin monomer-fibrinogen complex in patients with abdominal aortic aneurysm. J Vasc Surg. 2005;42(2):200-205. PubMed, CrossRef
  31. Hardy M, Lecompte T, Douxfils J, Lessire S, Dogné JM, Chatelain B, Testa S, Gouin-Thibault I, Gruel Y, Medcalf RL, Ten Cate H, Lippi G, Mullier F. Management of the thrombotic risk associated with COVID-19: guidance for the hemostasis laboratory. Thromb J. 2020;18:17. PubMed, PubMedCentral, CrossRef
  32. McDuffie FC, Giffin C, Niedringhaus R, Mann KG, Owen CA Jr, Bowie EJ, Peterson J, Clark G, Hunder GG. Prothrombin, thrombin and prothrombin fragments in plasma of normal individuals and of patients with laboratory evidence of disseminated intravascular coagulation. Thromb Res. 1979;16(5-6):759-773. PubMed, CrossRef
  33. Hong LZ, Shou ZX, Zheng DM, Jin X. The most important biomarker associated with coagulation and inflammation among COVID-19 patients. Mol Cell Biochem. 2021;476(7):2877-2885. PubMed, PubMedCentral, CrossRef
  34. Kwaan HC, Lindholm PF. The Central Role of Fibrinolytic Response in COVID-19-A Hematologist’s Perspective. Int J Mol Sci. 2021;22(3):1283. PubMed, PubMedCentral, CrossRef
  35. Christiaans SC, Wagener BM, Esmon CT, Pittet JF. Protein C and acute inflammation: a clinical and biological perspective. Am J Physiol Lung Cell Mol Physiol. 2013;305(7):L455-L466. PubMed, CrossRef
  36. Grobbelaar LM, Venter Ch, Vlok M, Ngoepe M, Laubscher GJa, Petrus Lourens PJ, Steenkamp J, Kell DB, Pretorius E. SARS-CoV-2 spike protein S1 induces fibrin(ogen) resistant to fibrinolysis: Implications for microclot formation in COVID. medRxiv. 2021;03.05.21252960. CrossRef
  37. Bachler M, Bösch J, Stürzel DP, Hell T, Giebl A, Ströhle M, Klein SJ, Schäfer V, Lehner GF, Joannidis M, Thomé C, Fries D. Impaired fibrinolysis in critically ill COVID-19 patients. Br J Anaesth. 2021;126(3):590-598. PubMed, PubMedCentral, CrossRef
  38. Mazzeffi M, Chow JH, Amoroso A, Tanaka K. Revisiting the Protein C Pathway: An Opportunity for Adjunctive Intervention in COVID-19? Anesth Analg. 2020;131(3):690-693. PubMed, PubMedCentral, CrossRef
  39. Griffin JH, Lyden P. COVID-19 hypothesis: Activated protein C for therapy of virus-induced pathologic thromboinflammation. Res Pract Thromb Haemost. 2020;4(4):506-509. PubMed, PubMedCentral, CrossRef
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