Gistin Khusnul Khatimah(1*), Joserizal Serudji(2), Vaulinne Basyir(3)

(1) Prodi Program Pendidikan Dokter Spesialis Obstetri dan Ginekologi Fakultas Kedokteran Universitas Andalas RSUP Dr. M. Djamil Padang
(2) Sub Division of Fetomaternal Medicine, Obstetrics and Gynecology Department, Faculty of Medicine, Andalas University, Dr. M. Djamil Central General Hospital Padang, West Sumatera, Indonesia
(3) Sub Division of Fetomaternal Medicine, Obstetrics and Gynecology Department, Faculty of Medicine, Andalas University, Dr. M. Djamil Central General Hospital Padang, West Sumatera, Indonesia
(*) Corresponding Author

DOI: https://doi.org/10.25077/aoj.6.1.27-34.2022


Introduction: Preeclampsia is a condition caused by alterations in endothelial function during pregnancy. Changes in endothelial function result in an increase in coagulation and microvascular fibrin accumulation, which results in impaired placental perfusion. Thrombin, which converts fibrin to fibrinogen, as well as platelet activity, the fibrinolytic system, and anticoagulants, are all procoagulant circumstances in preeclampsia. Thrombin contributes to the pathogenesis of preeclampsia by increasing the expression of sFlt-1 thereby providing an antiangiogenic response. Protease Activated Receptor-1 (PAR-1) is a mediator of thrombin for coagulation and inflammation in preeclampsia. Inhibition of Protease Activated Receptor-1 expression in trophoblasts can enhance placental angiogenesis and vascular remodeling. Recently, only few studies have assessed the levels of Protease Activated Receptor -7 and thrombin in preeclampsia.

Objective: To determine the difference in levels of Protease Activated Receptor-1 and thrombin in preeclampsia and normal pregnancy

Methods: This study is observational with a cross-sectional comparative study design. Sampling was conducted from March 2020 to March 2021. A total of 66 patients were investigated, with 33 samples of preeclampsia and 33 samples of normal pregnancy. The independent sample T-test was used for statistical analysis.

Results: The mean levels of Protease Activated Receptor-1 in the preeclampsia group were higher at 28.56 ± 7.68 ng/mL while normal pregnancy was 21.67 ± 6.92 ng/mL. The results of statistical tests showed that there was a significant difference in levels of Protease Activated Receptor-1 between the preeclampsia and normal pregnancy groups (p<0.05). The mean thrombin level in the preeclampsia group was higher at 72.23 ± 7.99 ng/mL, while in normal pregnancy it was 63.70 ± 8.92 ng/mL. The difference in thrombin levels between the preeclampsia and normal pregnancy groups was statistically significant (p<0.05).

Conclusion: Preeclampsia was associated with greater levels of Protease Activated Receptor-1 and thrombin than normal pregnancy. There was a significant difference in the mean levels of Protease Activated Receptor-1 and thrombin between preeclampsia and normal pregnancy.

Keywords: Thrombin, Protease Activated Receptor-1(PAR-1), Preeclampsia

Full Text:



Cunningham FG. Williams Obstetrics. 24th ed. (Cunningham FG, ed.). New York: McGraw-Hill Medical; 2014

Nursal D, Tamela P, Fitrayeni. Risk factor of preeclampsia in pregnant women at RSUP Dr. M Djamil Padang 2014. JKMA. 2014:38-44.

Anggaraini DG, Tamela P, Fitrayeni. Risk factor of preeclampsia in pregnant women at RSUP Dr. M Djamil Padang 2014. Journal of Andalas Public Health; 2015

Levine RJ, Lim K-H, Schisterman EF, Sachs BP, Sibai BM, Karumanchi SA. Circulating Angiogenic Factors and the Risk of Preeclampsia. The New England Journal of Medicine. 2004;12.

Marchi RR, Ramirez YL. Haemostatic changes related to fibrin formation and fibrinolysis during the first trimester in normal prenancy and in reccurent miscarriage. US Natl Libr Med Natl institutes Heal. 2017;97(4).

Gardiner C, Vatish M. Impact of haemostatic mechanisms on pathophysiology of preeclampsia. Thromb Res. 2017;151(1):S48-S52. doi:10.1016/S0049-3848(17)30067-1

Erez O, Romero R, Kim SS, et al. Over-expression of the thrombin receptor (PAR-1) in the placenta in preeclampsia: A mechanism for the intersection of coagulation and inflammation. J Matern Neonatal Med. 2008;21(6):345- 355

Heuberger DM, Schuepbach Ra. Protease-activated receptors (PARs): mechanisms of action and potential therapeutic modulators in PAR-driven inflammatory diseases. Thromb J. 2019 Mar 29;17:4.

Zhao Y, Zheng Y, Liu X, Luo Q, Wu D, Liu X, et al. Inhibitingtrophoblast PAR-1 overexpression suppresses sFlt-1-induced anti- angiogenesis and abnormal vascular remodeling: a possible therapeutic approach for preeclampsia. MHR: Basic science of reproductive medicine. 2018 Mar 1;24(3):158–69.

Ismail SK, Higgins JR. Hemostasis in Pre-Eclampsia. Semin Thromb Hemost. 2011;37(2):111-117.

Tanjung MT, Siddik HD, Hariman H, Koh SCL. Coagulation and fibrinolysis in preeclampsia and neonates. Clin Appl Thromb. 2005;11(4):467- 473.

Murray EKI, Murphy MSQ, Smith GN, Graham CH, Othman M. Thromboelastographic analysis of haemostasis in preeclamptic and normotensive pregnant women. Blood Coagul Fibrinolysis. 2018;29(6):567- 572.

Perucci LO, Vieira ELM, Teixeira AL, Gomes KB, Dusse LM, Sousa LP. Decreased plasma concentrations of brain-derived neurotrophic factor in preeklampsia Clinica Chimica Acta 2017;464:142-7.

Utama, Sri Yun. Risk factor of Severe Preeclampsia in pregnant women in RSD Raden Mattaher Jambi, 2017. Scientific Journal of Batanghari University Jambi. Vol. 8, no. 2, pp.71-79

Artikasari, Kurniawati. The relationship between primigravida and the incidence of preeclampsia/eclampsia in RSUD DR. Moewardi Surakarta since 1 January until 31 December 2008. Thesis. Surakarta. Muhammadiyah University, Surakarta. 2009.

Bastani, P., Kobra, H., Hossein, N. Risk Factors for Preeclampsia in Multigravida Woman. Research Journal of Biological Sciences. vol.3, no. 1. 2008. p; 148-153.

Denantika, O., Serudji, J., Revilla, G. Relationship between Gravida Status and Maternal Age on the Incidence of Preeclampsia at RSUP Dr.M. Djamil Padang on 2012-2013. Andalas Health Journal. Vol. 4, no. 1, 2015. p: 212-217

Sohlberg S, Stephansson O, Cnattingius S, et al. Maternal body mass index, height, and risks of preeclampsia. Am J Hypertens 25(1). 2012 p: 120- 125.

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(8):1549-1557.

Solomon C, Collis RE, Collins PW. Haemostatic monitoring during postpartum haemorrhage and implications for management. Br J Anaesth. 2012;109(6):851-863.

Sugimura M. Is thrombin a “toxin” in the pathogenesis of preeclampsia? Hypertens Res Pregnancy. 2015;3(1):13-18.

Liu G, Gurung AS, Qiu W. Lateral flow aptasensor for simultaneous detection of platelet-derived growth factor-BB (PDGF-BB) and thrombin. Molecules. 2019;24(4).

Winter WE, Greene DN, Beal SG, et al. Clotting factors: Clinical biochemistry and their roles as plasma enzymes. In: Makowski GS, ed. Advances in Clinical Chemistry. Vol 94. 1st ed. Elsevier Inc.; 2020:31-84.

Duarte RCF, Ferreira CN, Rios DRA, Reis HJ dos, Carvalho M das G. Thrombin generation assays for global evaluation of the hemostatic system: perspectives and limitations. Rev Bras Hematol Hemoter. 2017;39(3):259- 265.


  • There are currently no refbacks.

Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 International License.

Address for Correspondence:

Editorial Room Andalas Obstetrics and Gynecology Journal 3rd floor of KSM Obstetrics and Gynecology
RSUP Dr. M. Djamil Padang, Jl. Perintis Kemerdekaan Padang, Sumatara Barat, 25127