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Changes in coagulation and hemodynamics during pregnancy: a prospective longitudinal study of 58 cases

  • Maternal-Fetal Medicine
  • Published:
Archives of Gynecology and Obstetrics Aims and scope Submit manuscript

Abstract

Purpose

To investigate changes and establish reference values in coagulation, anticoagulation, fibrinolysis, anti-fibrinolysis and hemodynamics during normal pregnancy.

Methods

A total of 58 women with singleton pregnancies were recruited. Blood and ultrasound examinations were performed in the 10th–14th, 20th–24th, and 30th–34th weeks of pregnancy. The same examinations were performed in 50 non-pregnant women who were selected as the control group.

Results

Levels of fibrinogen, thrombin time, fibronectin, prothrombin activated fragments 1+2 and thrombomodulin were higher in early pregnancy than those in the control group (P < 0.05). Fibrinogen, prothrombin time, activated partial thromboplastin time, thrombin time, thromboxane B2, prothrombin activated fragments 1+2, thrombomodulin, D-dimer, and plasminogen activator inhibitor-2 were statistically different between the mid pregnancy and the control group (P < 0.05). Meanwhile, fibrinogen, prothrombin time, activated partial thromboplastin time, thrombin time, fibronectin, thromboxane B2, prothrombin activated fragments 1+2, thrombomodulin, and plasminogen activator inhibitor-2 were obviously elevated in late pregnancy as compared with the control group (P < 0.05). Moreover, fibrinogen, thromboxane B2, prothrombin activated fragment 1+2, D-dimer plasminogen, and activator inhibitor-2 gradually increased during pregnancy with some fluctuation. Prothrombin time, activated partial thromboplastin time, thrombin time, international normalized ratio, and thrombomodulin as well as systolic/diastolic ratio, pulsatility index, and resistance index in uterine arteries showed a tendency to decrease in pregnant women.

Conclusions

Coagulation, anti-coagulation, fibrinolytic and anti-fibrinolytic activities are enhanced and balanced at a higher level during pregnancy. In addition, uterine artery and umbilical artery hemodynamics become more baby friendly (i.e., high flow and low resistance).

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References

  1. Greer IA (1999) Thrombosis in pregnancy: maternal and fetal issues. Lancet 353:1258–1265

    Article  PubMed  CAS  Google Scholar 

  2. Pabinger I (2009) Thrombophilia and its impact on pregnancy. Thromb Res 123:S16–S21

    Article  PubMed  CAS  Google Scholar 

  3. Said JM (2011) The role of proteoglycans in contributing to placental thrombosis and fetal growth restriction. J Pregnancy 2011:928381

    PubMed  Google Scholar 

  4. James AH (2009) Pregnancy-associated thrombosis. Hematol Am Soc Hematol Educ Progr 2009:277–285

    Article  Google Scholar 

  5. Rodger M (2010) Evidence base for the management of venous thromboembolism in pregnancy. Hematol Am Soc Hematol Educ Progr 2010:173–180

    Article  Google Scholar 

  6. Vora S, Ghosh K, Shetty S, Salvi V, Satoskar P (2007) Deep venous thrombosis in the antenatal period in a large cohort of pregnancies from western India. Thromb J 5:9

    Article  PubMed  Google Scholar 

  7. Stortoni P, Cecati M, Giannubilo SR, Sartini D, Turi A, Emanuelli M, Tranquilli AL (2010) Placental thrombomodulin expression in recurrent miscarriage. Reprod Biol Endocrinol 8:1

    Article  PubMed  Google Scholar 

  8. Sucak GT, Acar K, Sucak A, Kirazli S, Haznedar R (2006) Increased global fibrinolytic capacity as a clue for activated fibrinolysis in pre-eclampsia. Blood Coagul Fibrinolysis 17:347–352

    Article  PubMed  CAS  Google Scholar 

  9. Wikström AK, Nash P, Eriksson UJ, Olovsson MH (2009) Evidence of increased oxidative stress and a change in the plasminogen activator inhibitor (PAI)-1 to PAI-2 ratio in early-onset but not late-onset preeclampsia. Am J Obstet Gynecol 201:5971.e1–5971.e8

    Article  Google Scholar 

  10. Villarreal C, García-Aguirre G, Hernández C, Vega O, Borbolla JR, Collados MT (2002) Congenital thrombophilia associated to obstetric complications. J Thromb Thrombolysis 14:163–169

    Article  PubMed  Google Scholar 

  11. Alijotas-Reig J, Vilardell-Tarres M (2010) Is obstetric antiphospholipid syndrome a primary nonthrombotic, proinflammatory, complement-mediated disorder related to antiphospholipid antibodies? Obstet Gynecol Surv 65:39–45

    Article  PubMed  Google Scholar 

  12. Borrelli AL, De Lucia D, Bernacchi M, Napolitano M, Di Domenico A, Felicetti M, Ferrara C, Meo D, Raffio R, Rivetti A, Sessa M, Tagliaferri A, Torella M (2006) Haemocoagulative modifications correlated with pregnancy. Minerva Ginecol 58(4):315–322

    PubMed  CAS  Google Scholar 

  13. Cerneca F, Ricci G, Simeone R, Malisano M, Alberico S, Guaschino S (1997) Coagulation and fibrinolysis changes in normal pregnancy. Increased levels of procoagulants and reduced levels of inhibitors during pregnancy induce a hypercoagulable state, combined with a reactive fibrinolysis. Eur J Obstet Gynecol Reprod Biol 73:31–36

    Article  PubMed  CAS  Google Scholar 

  14. Yoshida A, Nakao S, Kobayashi M, Kobayashi H (2000) Flow-mediated vasodilation and plasma fibronectin levels in preeclampsia. Hypertension 36:400–404

    PubMed  CAS  Google Scholar 

  15. Pulkkinen MO, Lehto M, Jalkanen M, Näntö-Salonen K (1984) Collagen types and fibronectin in the uterine muscle of normal and hypertensive pregnant patients. Am J Obstet Gynecol 149:711–717

    PubMed  CAS  Google Scholar 

  16. Dane C, Buyukasik H, Dane B, Yayla M (2009) Maternal plasma fibronectin and advanced oxidative protein products for the prediction of preeclampsia in high risk pregnancies: a prospective cohort study. Fetal Diagn Ther 26:189–194

    Article  PubMed  Google Scholar 

  17. Bowen RS, Zhang Y, Gu Y, Lewis DF, Wang Y (2005) Increased phospholipase A2 and thromboxane but not prostacyclin production by placental trophoblast cells from normal and preeclamptic pregnancies cultured under hypoxia condition. Placenta 26:402–409

    Article  PubMed  CAS  Google Scholar 

  18. Zhao S, Gu Y, Lewis DF, Wang Y (2008) Predominant basal directional release of thromboxane, but not prostacyclin, by placental trophoblasts from normal and preeclamptic pregnancies. Placenta 29:81–88

    Article  PubMed  Google Scholar 

  19. Maiello M, Torella M, Caserta L, Caserta R, Sessa M, Tagliaferri A, Bernacchi M, Napolitano M, Nappo C, De Lucia D, Panariello S (2006) Hypercoagulability during pregnancy: evidences for a thrombophilic state. Minerva Ginecol 58:417–422

    PubMed  CAS  Google Scholar 

  20. Kjellberg U, Andersson N, Rosén S, Tengborn L, Hellgren M (1999) APC resistance and other haemostatic variables during pregnancy and puerperium. Thromb Haemost 81:527–531

    PubMed  CAS  Google Scholar 

  21. Brenner B (2004) Haemostatic changes in pregnancy. Thromb Res 114:409–414

    Article  PubMed  CAS  Google Scholar 

  22. Boffa MC, Valsecchi L, Fausto A, Gozin D, Vigano′ D′Angelo S, Safa O, Castiglioni MT, Amiral J, D′Angelo A (1998) Predictive value of plasma thrombomodulin in preeclampsia and gestational hypertension. Thromb Haemost 79:1092–1095

    PubMed  CAS  Google Scholar 

  23. Rousseau A, Favier R, Van Dreden P (2009) Elevated circulating soluble thrombomodulin activity, tissue factor activity and circulating procoagulant phospholipids: new and useful markers for pre-eclampsia? Eur J Obstet Gynecol Reprod Biol 146:46–49

    Article  PubMed  CAS  Google Scholar 

  24. Nadar SK, Al Yemeni E, Blann AD, Lip GYH (2004) Thrombomodulin, von Willebrand factor and E-selectin as plasma markers of endothelial damage/dysfunction and activation in pregnancy induced hypertension. Thromb Res 113:123–128

    Article  PubMed  CAS  Google Scholar 

  25. Hunt BJ, Missfelder-Lobos H, Parra-Cordero M, Fletcher O, Parmar K, Lefkou E, Lees CC (2009) Pregnancy outcome and fibrinolytic, endothelial and coagulation markers in women undergoing uterine artery Doppler screening at 23 weeks. J Thromb Haemost 7:955–961

    Article  PubMed  CAS  Google Scholar 

  26. Coolman M, de Groot CJ, Steegers EA, Geurts-Moespot A, Thomas CM, Steegers-Theunissen RP, Sweep FC (2006) Concentrations of plasminogen activators and their inhibitors in blood preconceptionally, during and after pregnancy. Eur J Obstet Gynecol Reprod Biol 128:22–28

    Article  PubMed  CAS  Google Scholar 

  27. Chinni E, Colaizzo D, Tiscia GL, Martinelli P, Maruotti GM, Matteo M, Margaglione M, Grandone E (2010) Markers of haemostasis and angiogenesis in placentae from gestational vascular complications: impairment of mechanisms involved in maintaining intervillous blood flow. Thromb Res 125:267–271

    Article  PubMed  CAS  Google Scholar 

  28. Nielsen AH, Schauser KH, Poulsen K (2000) Current topic: the uteroplacental renin-angiotensin system. Placenta 21:468–477

    Article  PubMed  CAS  Google Scholar 

  29. Myatt L (1992) Control of vascular resistance in the human placenta. Placenta 13:329–341

    Article  PubMed  CAS  Google Scholar 

  30. Rizzo G, Capponi A, Cavicchioni O, Vendola M, Arduini D (2008) First trimester uterine Doppler and three-dimensional ultrasound placental volume calculation in predicting pre-eclampsia. Eur J Obstet Gynecol Reprod Biol 38:147–151

    Article  Google Scholar 

  31. Dugoff L, Lynch AM, Cioffi-Ragan D, Hobbins JC, Schultz LK, Malone FD, D′Alton ME; FASTER Trial Research Consortium (2005) First trimester uterine artery Doppler abnormalities predict subsequent intrauterine growth restriction. Am J Obstet Gynecol 193:1208–1212

    Google Scholar 

  32. Misra VK, Hobel CJ, Sing CF (2009) Placental Blood Flow and the Risk of Preterm Delivery. Placenta 30:619–624

    Article  PubMed  CAS  Google Scholar 

  33. Fratelli N, Rampello S, Guala M, Platto C, Frusca T (2008) Transabdominal uterine artery Doppler between 11 and 14 weeks of gestation for the prediction of outcome in high-risk pregnancies. J Matern Fetal Neonatal Med 21:403–406

    Article  PubMed  CAS  Google Scholar 

  34. Lees C, Parra M, Missfelder-Lobos H, Morgans A, Fletcher O, Nicolaides KH (2001) Individualized risk assessment for adverse pregnancy outcome by uterine artery Doppler at 23 weeks. Obstet Gynecol 98:369–373

    Article  PubMed  CAS  Google Scholar 

  35. Tchirikov M, Strohner M, Förster D, Hüneke B (2009) A combination of umbilical artery PI and normalized blood flow volume in the umbilical vein: venous-arterial index for the prediction of fetal outcome. Eur J Obstet Gynecol Reprod Biol 142:129–133

    Article  PubMed  Google Scholar 

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Acknowledgments

This work was supported by the tenth-five-years national key scientific and technology projects of the National Department of Technology (2004BA720A06-01), the grants of National Natural Science Foundation of China (81000259, 30973207 and 81070746) and Guangdong Natural Science Foundation (10151008901000007 and 10451008901004246), Fundamental Research Funds for the Central Universities (3161001), and Research Fund for the Doctoral Program of Higher Education of China (20090171120075).

Conflict of interest

None of the authors have no actual or potential conflict of interest.

Author information

Authors and Affiliations

  1. Department of Obstetrics and Gynecology, Sun Yat-sen Memorial Hospital of Sun Yat-sen University, Yanjiang Road 107, Guangzhou, Guangdong, People’s Republic of China

    Chen Hui, Meng Lili, Chen Libin, Zhang Rui & Zhang Jianping

  2. Department of Gynecology and Obstetrics, Guangzhou Women and Children’s Medical Center, Guangzhou, People’s Republic of China

    Guo Fang

  3. Department of Clinical Laboratory, The First Affiliated Hospital of Sun Yat-Sen University, Guangzhou, People’s Republic of China

    Gao Ling

  4. Department of Laboratory Medicine, The First Affiliated Hospital of Sun Yat-Sen University, Zhongshan Road II 58, Guangzhou, Guangdong, People’s Republic of China

    Gao Ling

Authors
  1. Chen Hui
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  2. Meng Lili
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  3. Chen Libin
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  4. Zhang Rui
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  5. Guo Fang
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  6. Gao Ling
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  7. Zhang Jianping
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Corresponding author

Correspondence to Zhang Jianping.

Additional information

C. Hui and M. Lili contributed equally to this study.

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Hui, C., Lili, M., Libin, C. et al. Changes in coagulation and hemodynamics during pregnancy: a prospective longitudinal study of 58 cases. Arch Gynecol Obstet 285, 1231–1236 (2012). https://doi.org/10.1007/s00404-011-2137-x

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  • DOI: https://doi.org/10.1007/s00404-011-2137-x

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