Association of Serum Protein C and Protein S Level in Unexplained Recurrent Pregnancy Loss

Author(s): Dr. Mousumi Saha, Dr. Jesika Rizvi Tamanna, Dr. khadiza Begum, Dr. Masuda Sultana, Dr. Surayea Bul-Bul, Prof. Dr. Md. Salauddin Shah, Prof. Dr. Nahreen Akhtar


Recurrent pregnancy loss (RPL) is an intense personal calamity to the couples and an arduous clinical challenge to the obstetricians. One of the greatest challenges is not being able to identify the baseline etiology of RPL when all the routine and recommended investigations return normal or negative. RPL affects about 1-3% of women of reproductive age trying to conceive. Thrombophilia has been identified as one of main causes of RPL. Inherited thrombophilia includes Protein C deficiency, Protein S deficiency are linked to RPL and could be associated with severe obstetric complications such as preeclampsia, intrauterine growth restriction, or stillbirth which are further associated with microvascular thrombosis in placental blood vessels. Protein C and Protein S deficiencies are associated with a variably increased risk of thrombosis and are inherited independently in an autosomal dominant trait.


The aim of the study was to determine the association of serum protein C and protein S level in patients with unexplained recurrent pregnancy loss.


A case control study was carried out in the outpatient Department of Feto-maternal Medicine, Bangabandhu Sheikh Mujib Medical University, Dhaka. After obtaining the ethical clearance from the Institutional Review Board, a convenient sampling technique was applied for data collection. According to the availability of the patients as per inclusion and exclusion criteria, 30 patients with RPL and 30 ages and BMI matched control was taken and necessary information was recorded in a structured questionnaire. With all aseptic precaution 2 ml of venous blood was collected from antecubital vein of each participant by trained blood collector of Department of Hematology, BSMMU, in a supplied coagulation vial. After centrifuging, supernatant plasma was used for mixing with protein C and protein S reagent. By clotting method using a fully automated coagulation analyzer Sysmex CS-1600 machine results were obtained. The results were noted in the questionnaire and data was analyzed using SPSS software.


Mean age and BMI of the RPL patients was 26.85±4.17 years and 25.03±2.42 Kg/m2, which was matched with the control groups. The study found that RPL patients experienced an average of 4 pregnancy losses and about 70% pregnancy loss occurred during first trimester. A total of 3(10%) protein C deficient, 5(16.7%) protein S deficient and 2(6.7%) both protein C and S deficient patient were found in the case group. The mean of Protein C and S level among RPL patients was 78.46±13.18 and 81.69±14.06 respectively, which was significantly lower than the control group level. Protein C and S level did not vary for patients experienced 1st trimester loss or 2nd trimester loss. The odds ratio for RPL group due to protein C and protein S deficiency was considerably higher [3.22, 95% CI: 0.32-32.89 for Protein C and 5.80, 95% CI: 0.64-53.01 for PS] and a significant association of protein C and protein S level with RPL was found with adjusted binary logistic regression.


The present study found higher incidence of protein C and S deficiency among RPL patients with most of the miscarriage occurring in the first trimester. Hence, pregnant women should be tested for protein C and S deficiencies after excluding common causes of RPL and treated accordingly.

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