Ukr.Biochem.J. 2023; Volume 95, Issue 3, May-Jun, pp. 33-41

doi: https://doi.org/10.15407/ubj95.03.033

Validation of the diagnostics algorithm to monitor coagulation parameters in pregnant women

06.07.2023   Uncategorized   No comments

D. S. Korolova1, A. O. Pavlenko1, A. Altorjay2, S. I. Zhuk3,
I. V. Us3, Y. Tsaryk1, A. Suranyi2, V. O. Chernyshenko1*

1Palladin Institute of Biochemistry, National Academy of Sciences of Ukraine, Kyiv;
2Albert Szent-Györgyi Medical School, University of Szeged, Hungary;
3P. L. Shupyk National Medical Academy of Postgraduate Education, Kyiv, Ukraine;
*e-mail: bio.cherv@gmail.com

Received: 19 May 2023; Revised: 05 June 2023;
Accepted: 07 June 2023; Available on-line: 11 July 2023

Thrombotic events are among the most dangerous complications of pregnancy. Therefore, selection of appropriate tests and standardization of techniques used for accurate diagnostics of blood coagulation system state is of great importance. In this present study, we monitored several molecular markers of the dangers of intravascular thrombus formation and estimated the platelet function in pregnant women during­ gestation. We performed independent measurements using the same methodology for different cohorts of patients recruited in Kyiv (Ukraine) and in Szeged (Hungary). D-dimer and soluble fibrin were measured using ELISA. Protein C (PC) level was estimated using chromogenic substrate assay. Fibrinogen concentration was measured by spectrophotometry using thrombin-like enzyme. Platelet function was estimated by aggregometry­. Statistical data analysis was performed using the Kruskal-Wallis test. Statistically significant increases of fibrinogen concentration from first to third gestational trimester was shown for both studied cohorts of patients (5-6 mg/ml at third trimester on average). Applied methods allowed us to detect the same tendencies of decreases in PC level as well as the appearance of moderate amounts of D-dimer (up to 300 ng/ml) and SF (up to 10-15 ug/ml). Platelet function was increased on the first trimester of pregnancy and decreased during­ following trimesters slightly. Results indicated the changes in the blood coagulation system of pregnant women during gestation with the same effectiveness independently of the selected cohorts, time and place of measurements. The application of the proposed diagnostics algorithm may allow estimating the risk of thrombotic complications during pregnancy.

Keywords: , , , , ,

References:

  1. Say L, Chou D, Gemmill A, Tunçalp Ö, Moller AB, Daniels J, Gülmezoglu AM, Temmerman M, Alkema L. Global causes of maternal death: a WHO systematic analysis. Lancet Glob Health. 2014;2(6):e323-e333. PubMed, CrossRef
  2. Robert-Ebadi H, Moumneh T, Le Gal G, Righini M. Diagnosis of Pulmonary Embolism during Pregnancy. Diagnostics (Basel). 2022;12(8):1875. PubMed, PubMedCentral, CrossRef
  3. Simcox LE, Ormesher L, Tower C, Greer IA. Pulmonary thrombo-embolism in pregnancy: diagnosis and management. Breathe (Sheff). 2015;11(4):282-289. PubMed, PubMedCentral, CrossRef
  4. Pabinger I, Grafenhofer H. Thrombosis during pregnancy: risk factors, diagnosis and treatment. Pathophysiol Haemost Thromb. 2002;32(5-6):322-324. PubMed, CrossRef
  5. Robert-Ebadi H, Le Gal G, Righini M. Diagnostic Management of Pregnant Women With Suspected Pulmonary Embolism. Front Cardiovasc Med. 2022;9:851985. PubMed, PubMedCentral, CrossRef
  6. Khan F, Vaillancourt C, Bourjeily G. Diagnosis and management of deep vein thrombosis in pregnancy. BMJ. 2017;357:j2344. PubMed, CrossRef
  7. Kline JA, Williams GW, Hernandez-Nino J. D-dimer concentrations in normal pregnancy: new diagnostic thresholds are needed. Clin Chem. 2005;51(5):825-829. PubMed, CrossRef
  8. Greer IA. Thrombosis in pregnancy: updates in diagnosis and management. Hematology Am Soc Hematol Educ Program. 2012;2012:203-207. PubMed, CrossRef
  9. Bremme KA. Haemostatic changes in pregnancy. Best Pract Res Clin Haematol. 2003;16(2):153-168. PubMed, CrossRef
  10. Konkle BA. Diagnosis and management of thrombosis in pregnancy. Birth Defects Res C Embryo Today. 2015;105(3):185-189. PubMed, CrossRef
  11. Komisarenko SV, Dieiev VA, Lugovskoi EV, Kolesnikova IM, Platonova TM, Lugovska NE, Kostiuchenko OP, Chernyshenko VO, Korolova DS, Chernyshenko TM, Liksunov OV, Kashyrova OV, Romanova EE. Application of immunoenzymatic methods for laboratory diagnostics of the threat of intravascular thrombus formation. K.: Publisher Bykhun VY, 2019. 36 p. (In Ukrainian).
  12. Us IV, Zhuk SI, Korolova DS, Platonov OM, Tsaryk YuО. Platelet hemostasis in the implementation of placental dysfunction. Reprod Health Woman. 2022;6(61):6-12. (In Russian). CrossRef
  13. Korolova DS, Stohnii YM, Gryshchuk VI, Zhuk SI, Us IV, Chernyshenko TM, Kostiuchenko OP, Klymenko KP, Platonov OM, Ivashchenko OI, Chernyshenko VO. Thromboelastographic study of fibrin clot and molecular basis of maximum clot firmness. Ukr Biochem J. 2021;93(2):62-70. CrossRef
  14. Aksonova AV, Ventskivska IB, Platonova TM, Kolesnikova IM, Nalozhytova OO.The complex evaluation of lipid metabolism and blood coagulation system indicators for prediction and early diagnosis of the preeclampsia. ScienceRise: Med Sci. 2016;(12(8)):40-46. (In Ukrainian). CrossRef
  15. Sokolovska AS, Chernyshenko TM, Ivanenko TI. Comparative characteristic of fibrinogen level determination methods in blood plasma. Exper Clin Phisiol Biochem. 2002; 3: 82-86.
  16. Lugovskoy 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
  17. Lugovskoy EV, Kolesnikova IN, Lugovskaia NE, Litvinova LM, Gritsenko PG, Gogolinskaia GK, Liashko ED, Kostiuchenko EP, Remizovskiy GA, Pedchenko VN, Komisarenko SV. Quantification of D-dimer and soluble fibrin in blood plasma of people with ischemic heart disease and hypertension. Ukr Biokhim Zhurn. 2004;76(6):136-141. (In Russian). PubMed
  18. 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
  19. Born GV. Aggregation of blood platelets by adenosine diphosphate and its reversal. Nature. 1962;194:927-929. PubMed, CrossRef
  20. Siennicka A, Kłysz M, Chełstowski K, Tabaczniuk A, Marcinowska Z, Tarnowska P, Kulesza J, Torbe A, Jastrzębska M. Reference Values of D-Dimers and Fibrinogen in the Course of Physiological Pregnancy: the Potential Impact of Selected Risk Factors-A Pilot Study. Biomed Res Int. 2020;2020:3192350. PubMed, PubMedCentral, CrossRef
  21.  Gutiérrez García I, Pérez Cañadas P, Martínez Uriarte J, García Izquierdo O, Angeles Jódar Pérez M, García de Guadiana Romualdo L. D-dimer during pregnancy: establishing trimester-specific reference intervals. Scand J Clin Lab Invest. 2018;78(6):439-442. PubMed, CrossRef
  22. Urban G, Ku DH, Arkel Y, Rebarber A, Lockwood CJ, Paidas MJ. Elevated first trimester maternal levels of soluble fibrin polymer are associated with lower birthweight in twin gestation. Blood Coagul Fibrinolysis. 2006;17(5):343-346. PubMed, PubMedCentral, CrossRef
  23. Lugovskoy EV, Kolesnikova IN, Lugovskaia NE, Gritsenko PG, Litvinova LM, Gogolinskaia GK, Liashko ED, Kostiuchenko EP, Golota VIa, Kurochka VV, Komisarenko SV. Soluble fibrin and D-dimer at normal pregnancy and pregnancy with risk of miscarriage. Ukr Biokhim Zhurn. 2006;78(4):120-129. (In Russian). PubMed
  24. Mukhtar B, Garg R, Ibrahim G, Batra J. Investigating protein C and S levels in pregnant women with recurrent early pregnancy loss versus normal pregnancy. J Med Life. 2023;16(1):160-166. PubMed, PubMedCentral, CrossRef
  25. Forstner D, Guettler J, Gauster M. Changes in Maternal Platelet Physiology during Gestation and Their Interaction with Trophoblasts. Int J Mol Sci. 2021;22(19):10732. PubMed, PubMedCentral, CrossRef
  26. Blomqvist LRF, Strandell AM, Baghaei F, Hellgren MSE. Platelet aggregation in healthy women during normal pregnancy – a longitudinal study. Platelets. 2019;30(4):438-444. PubMed, CrossRef
  27. Swanepoel AC, Pretorius E. Ultrastructural analysis of platelets during three phases of pregnancy: a qualitative and quantitative investigation. Hematology. 2015;20(1):39-47. PubMed, CrossRef
Creative CommonsThis work is licensed under a Creative Commons Attribution 4.0 International License.