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The hemostatic parameters in pregnant women with different types of diabetes mellitus

https://doi.org/10.14341/DM12682

Abstract

BACKGROUND: The prevalence of diabetes mellitus (DM) in pregnancy is on the rise. Despite that gestational hypercoagulability is a physiological condition, diabetic pregnancy is associated with a high risk of venous thromboembolic complications (VTEC). There are many surveys related to the hemostatic parameters in non-pregnant women, but studies in pregnant women are not enough.

AIMS: To assess the coagulation and vascular-platelet hemostasis parameters in pregnant women with various types of diabetes mellitus, taking into account its correction method. The data were compared with these indicators in women with preeclampsia and healthy pregnant women at the same gestational age.

MATERIALS AND METHODS: An observational, single-center, retrospective cohort study was carried out at D.O. Ott ­Research Institute of Obstetrics, Gynecology, and Reproductive Medicine. The study included 1994 pregnant women who presented several groups taking into account the type of DM and its correction method, a group of women with preeclampsia (PE), and healthy women. The analysis of clinical data was carried out at 28–32 gestational weeks from 2012 to 2017. The study’s primary endpoint was taken as indicators of fibrinogen content, prothrombin index, thrombin time, activated partial thromboplastin time (APTT), and international normalized ratio (INR) antithrombin III, D-dimer, von Willebrand factor, and fibronectin. Additionally, the incidence of VTEC during pregnancy and within six weeks after delivery, gestational arterial hypertension, preeclampsia, fetal growth restriction, premature birth, and stillbirth cases was assessed.

RESULTS: in pregnant women with various types of diabetes mellitus and preeclampsia, a state of pathological hypercoagulation was observed compared to the control group. These changes were characterized by an increase and activation of the following blood parameters: fibrinogen, the degree and rate of platelet aggregation, D-dimer, homocysteine, von Willebrand factor, and fibronectin. At the same time, the content of antithrombin III was significantly reduced in patients with DM. Correlation analysis established a direct relationship between the range of the studied factors with the degree of glycemic control and the frequency of obstetric complications.

CONCLUSIONS: Diabetes mellitus in pregnancy is associated with a hypercoagulation condition and overexpression in the synthesis of endothelial dysfunction markers. Moreover, the severity of these processes depends on the type of DM and the severity of metabolic disorders. In diabetic pregnancy, exceptional attention to coagulation indicators, regular monitoring, and preventive treatment is required in order to improve the perinatal outcomes.

About the Authors

R. V. Kapustin
The Research Institute of Obstetrics, Gynecology and Reproductology named after D.O. Ott; St. Petersburg State University
Russian Federation

Roman V. Kapustin, MD, PhD

3 Saint Petersburg, Mendeleyevskaya line, 199034

Researcher ID: G-3759-2015;

eLibrary SPIN: 7300-6260

 


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E. V. Kopteeva
St. Petersburg State University
Russian Federation

Ekaterina V. Kopteeva, clinical resident

Saint Petersburg

eLibrary SPIN: 9421-6407

 


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O. N. Arzhanova
The Research Institute of Obstetrics, Gynecology and Reproductology named after D.O. Ott; St. Petersburg State University
Russian Federation

Olga N. Arzhanova, MD, PhD, Professor

Saint Petersburg

eLibrary SPIN: 7910-6039


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A. V. Tiselko
The Research Institute of Obstetrics, Gynecology and Reproductology named after D.O. Ott
Russian Federation

Alena V. Tiselko, MD, PhD

Saint Petersburg

eLibrary SPIN: 9010-7276


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N. Е. Androsova
The Research Institute of Obstetrics, Gynecology and Reproductology named after D.O. Ott
Russian Federation

Nataliia E. Androsova

Saint Petersburg


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T. I. Oparina
The Research Institute of Obstetrics, Gynecology and Reproductology named after D.O. Ott
Russian Federation

Tatiana I. Oparina, PhD in Biology

Saint Petersburg

eLibrary SPIN: 2719-5432


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References

1. International Diabetes Federation. IDF Diabetes Atlas, 9th edn. Brussels, Belgium: International Diabetes Federation; 2019.

2. Shestakova MV, Vikulova OK, Zheleznyakova AV, et al. Diabetes epidemiology in Russia: what has changed over the decade? Ter Arkh. 2019;91(10):4-13. doi: https://doi.org/10.26442/00403660.2019.10.000364

3. Committee on Practice Bulletins — Obstetrics. ACOG Practice Bulletin No. 190: Gestational Diabetes Mellitus. Obstet Gynecol. 2018;131(2):e49-e64.

4. Johns EC, Denison FC, Norman JE, Reynolds RM. Gestational Diabetes Mellitus: Mechanisms, Treatment, and Complications. Trends Endocrinol Metab. 2018;29(11):743-754. doi: https://doi.org/10.1016/j.tem.2018.09.004

5. Konstantinides SV, Meyer G, Becattini C, et al. 2019 ESC Guidelines for the diagnosis and management of acute pulmonary embolism developed in collaboration with the European Respiratory Society (ERS). Eur Heart J. 2020;41(4):543-603. doi: https://doi.org/10.1093/eurheartj/ehz405

6. Ewins K, Ní Ainle F. VTE risk assessment in pregnancy. Res Pract Thromb Haemost. 2020;4(2):183-192. doi: https://doi.org/10.1002/rth2.12290

7. O’Shaughnessy F, Donnelly JC, Bennett K, et al. Prevalence of postpartum venous thromboembolism risk factors in an Irish urban obstetric population. J Thromb Haemost. 2019;17(11):1875-1885. doi: https://doi.org/10.1111/jth.14568

8. Silva-Reyna P. Enfermedad tromboembólica venosa en el embarazo. Rev Mex Anestesiol. 2020;43(1):41-47. doi: https://doi.org/10.35366/CMA201G

9. Christiansen LR, Collins KA. Pregnancy-Associated Deaths. Am J Forensic Med Pathol. 2006;27(1):11-19. doi: https://doi.org/10.1097/01.paf.0000203154.50648.33

10. Kevane B, Donnelly J, D’Alton M, et al. Risk factors for pregnancy-associated venous thromboembolism: a review. J Perinat Med. 2014;42(4). doi: https://doi.org/10.1515/jpm-2013-0207

11. Rodger M. Pregnancy and venous thromboembolism: ‘TIPPS’ for risk stratification. Hematology. 2014;2014(1):387-392. doi: https://doi.org/10.1182/asheducation-2014.1.387

12. Egan K, O’Connor H, Kevane B, et al. Elevated plasma TFPI activity causes attenuated TF-dependent thrombin generation in early onset preeclampsia. Thromb Haemost. 2017;117(08):1549-1557. doi: https://doi.org/10.1160/TH16-12-0949

13. Nowotny K, Jung T, Höhn A, et al. Advanced Glycation End Products and Oxidative Stress in Type 2 Diabetes Mellitus. Biomolecules. 2015;5(1):194-222. doi: https://doi.org/10.3390/biom5010194

14. Díaz-Pérez FI, Hiden U, Gauster M, et al. Post-transcriptional down regulation of ICAM-1 in feto-placental endothelium in GDM. Cell Adh Migr. 2016;10(1-2):18-27. doi: https://doi.org/10.1080/19336918.2015.1127467

15. Lemkes BA, Hermanides J, Devries JH, et al. Hyperglycemia: a prothrombotic factor? J Thromb Haemost. 2010;8(8):1663-1669. doi: https://doi.org/10.1111/j.1538-7836.2010.03910.x

16. Sultan AA, Tata LJ, West J, et al. Risk factors for first venous thromboembolism around pregnancy: a population-based cohort study from the United Kingdom. Blood. 2013;121(19):3953-3961. doi: https://doi.org/10.1182/blood-2012-11-469551

17. Bleau N, Patenaude V, Abenhaim HA. Risk of Venous Thromboembolic Events in Pregnant Patients with Autoimmune Diseases. Clin Appl Thromb. 2016;22(3):285-291. doi: https://doi.org/10.1177/1076029614553023

18. Son KH, Lim N‐K, Lee J‐W, et al. Comparison of maternal morbidity and medical costs during pregnancy and delivery between patients with gestational diabetes and patients with pre‐existing diabetes. Diabet Med. 2015;32(4):477-486. doi: https://doi.org/10.1111/dme.12656

19. Bai J, Ding X, Du X, Zhao X, et al. Diabetes is associated with increased risk of venous thromboembolism: A systematic review and meta-analysis. Thromb Res. 2015;135(1):90-95. doi: https://doi.org/10.1016/j.thromres.2014.11.003

20. Bell EJ, Folsom AR, Lutsey PL, et al. Diabetes mellitus and venous thromboembolism: A systematic review and meta-analysis. Diabetes Res Clin Pract. 2016;111:10-18. doi: https://doi.org/10.1016/j.diabres.2015.10.019

21. Gariani K, Mavrakanas T, Combescure C, et al. Is diabetes mellitus a risk factor for venous thromboembolism? A systematic review and meta-analysis of case–control and cohort studies. Eur J Intern Med. 2016;28:52-58. doi: https://doi.org/10.1016/j.ejim.2015.10.001

22. Won HS, Kim DY, Yang MS, et al. Pregnancy-Induced Hypertension, But Not Gestational Diabetes Mellitus, Is a Risk Factor for Venous Thromboembolism in Pregnancy. Korean Circ J. 2011;41(1):23. doi: https://doi.org/10.4070/kcj.2011.41.1.23

23. Dedov II, Shestakova MV, Mayorov AYu, et al. Standards of specialized diabetes care. Diabetes Mellitus. 2019;22(S1):1-144 (In Russ.). doi: https://doi.org/10.14341/DM221S1

24. Wieczór R, Wieczór AM, Kulwas A, Rość D. Type 2 Diabetes and Cardiovascular Factors Contrasted with Fibrinolysis Disorders in the Blood of Patients with Peripheral Arterial Disease. Medicina (B Aires). 2019;55(7):395. doi: https://doi.org/10.3390/medicina55070395

25. Kim JH, Bae HY, Kim SY. Clinical Marker of Platelet Hyperreactivity in Diabetes Mellitus. Diabetes Metab J. 2013;37(6):423. doi: https://doi.org/10.4093/dmj.2013.37.6.423

26. Liu BY, Jian YL, Zhong M, et al. Value of Coagulation Function and Fibrinolytic System Assessment in Patients with Gestational Diabetes Mellitus. Nan Fang Yi Ke Da XueXue Bao. 2007;27(1):35-37.

27. Domingueti CP, Dusse LMS, Carvalho MDG, et al. Diabetes mellitus: The linkage between oxidative stress, inflammation, hypercoagulability and vascular complications. J Diabetes Complications. 2016;30(4):738-745. doi: https://doi.org/10.1016/j.jdiacomp.2015.12.018

28. Gorar S, Alioglu B, Ademoglu E, et al. Is There a Tendency for Thrombosis in Gestational Diabetes Mellitus? J Lab Physicians. 2016;8(2):101-105. doi: https://doi.org/10.4103/0974-2727.180790

29. Dong C, Gu X, Chen F, et al. The variation degree of coagulation function is not responsible for extra risk of hemorrhage in gestational diabetes mellitus. J Clin Lab Anal. 2020;34(4). doi: https://doi.org/10.1002/jcla.23129

30. Bronisz A, Rosc D, Bronisz M, et al. Coagulation and fibrinolysis variables in pregnant women with type 1 diabetes mellitus. Med Sci Monit. 2008;14(11):574-579.

31. Tarim E, Bagis T, Kilicdag E, et al. Elevated plasma homocysteine levels in gestational diabetes mellitus. Acta Obstet Gynecol Scand. 2004;83(6):543-547. doi: https://doi.org/10.1111/j.0001-6349.2004.00540.x

32. Baboolall U, Zha Y, Gong X, et al. Variations of plasma D-dimer level at various points of normal pregnancy and its trends in complicated pregnancies. Medicine (Baltimore). 2019;98(23):e15903. doi: https://doi.org/10.1097/MD.0000000000015903

33. Bellart J, Gilabert R, Fontcuberta J, et al. Coagulation and Fibrinolysis Parameters in Normal Pregnancy and in Gestational Diabetes. Am J Perinatol. 1998;15(08):479-486. doi: https://doi.org/10.1055/s-2007-994069

34. Lucena FC, Lage EM, Teixeira PG, et al. Longitudinal assessment of D-dimer and plasminogen activator inhibitor type-1 plasma levels in pregnant women with risk factors for preeclampsia. Hypertens Pregnancy. 2019;38(1):58-63. doi: https://doi.org/10.1080/10641955.2019.1577435.

35. Jacobsen AF, Skjeldestad FE, Sandset PM. Incidence and risk patterns of venous thromboembolism in pregnancy and puerperium — a register-based case-control study. Am J Obstet Gynecol. 2008;198(2):233.e1-233.e7. doi: https://doi.org/10.1016/j.ajog.2007.08.041

36. Celewicz Z, Miazgowski T. Plasma fibronectin in pregnancy complicated by diabetes mellitus and preeclampsia. Ginekol Pol. 2008;79(7):472-476.

37. Rasanen JP, Snyder CK, Rao PV, et al. Glycosylated Fibronectin as a First-Trimester Biomarker for Prediction of Gestational Diabetes. Obstet Gynecol. 2013;122(3):586-594. doi: https://doi.org/10.1097/AOG.0b013e3182a0c88b

38. Spiel AO, Gilbert JC, Jilma B. Von Willebrand Factor in Cardiovascular Disease. Circulation. 2008;117(11):1449-1459. doi: https://doi.org/10.1161/CIRCULATIONAHA.107.722827.

39. Fu G, Yan Y, Chen L, et al. Shortened Activated Partial Thromboplastin Time and Increased Superoxide Dismutase Levels Are Associated with Type 2 Diabetes Mellitus. Ann Clin Lab Sci. 2018;48(4):469-477.

40. Sapkota B, Shrestha SK, Poudel S. Association of activated partial thromboplastin time and fibrinogen level in patients with type II diabetes mellitus. BMC Res Notes. 2013;6(1):485. doi: https://doi.org/10.1186/1756-0500-6-485

41. Tisel’ko AV. Sravnitel’nyj analiz effektivnosti razlichnyh rezhimov insulinoterapii saharnogo diabeta 1 tipa vo vremya beremennosti. Zhurnal akusherstva i zhenskih boleznej. 2012;1:90-95. (in Russ.).


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For citations:


Kapustin R.V., Kopteeva E.V., Arzhanova O.N., Tiselko A.V., Androsova N.Е., Oparina T.I. The hemostatic parameters in pregnant women with different types of diabetes mellitus. Diabetes mellitus. 2021;24(3):251-261. (In Russ.) https://doi.org/10.14341/DM12682

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