Is serum fibrinogen an affirmative marker for vaginal delivery without PPH?

DOI -10.21276/obgyn.2020.6.2.10 ISSN Print – 2454-2334; ISSN Online – 2454-2342 RESEARCH ARTICLE Is serum fibrinogen an affirmative marker for vaginal delivery without PPH? Rachna Agarwal, Neha Jaiswal, Rajarshi Kar, Alpana Singh, Himsweta Srivastava Correspondence: Dr. Rachna Agarwal, Professor. Department of Obstetrics and Gynaecology, University College of Medical Sciences and Guru Teg Bahadur Hospital, Delhi; Email - Distributed under Attribution-Non Commercial – Share Alike 4.0 International (CC BY-NC-SA 4.0) ABSTRACT Objective: This study was conducted to see whether predelivery serum fibrinogen is a positive marker for conception ending with ‘physiological’ blood loss instead of predicting PPH. Methods: Low-risk pregnant women after 24 weeks of gestation with singleton pregnancy were prospectively followed for spontaneous vaginal delivery. Predelivery blood samples collected antenatally were preserved for estimation of serum fibrinogen. We excluded patients with altered coagulation profile, anemia, thrombocytopenia, hypertension, gestational diabetes and cholestasis. Final analysis compared fibrinogen levels in non-PPH and PPH subjects (n=40 each). Results: The serum fibrinogen levels in non-PPH was 2.80±0.55g/L and in PPH group was 1.07±0.48g/L (p<0.001). Correlation of predelivery fibrinogen and blood loss among subjects predicted a negative correlation (r = −0.695, p<0.001). There were no PPH cases when serum fibrinogen level was >2.63g/L (sensitivity 82.5%, specificity 100%). Conclusions: Prenatal serum fibrinogen level above 2.6g/L is suggested as potential alert marker for maternal well being (with non-PPH) in vaginal delivery. Keywords: Fibrinogen, pregnancy, blood loss, PPH. Postpartum hemorrhage (PPH) remains one of the foremost causes of maternal mortality and morbidity throughout the world. Looking to the growing awareness of haemostatic challenges in pregnant patients, serum fibrinogen is one of the key hematological parameters being investigated in relation to PPH.1-7 Fibrinogen functions by activating platelet aggregation and initiating fibrin polymerization. Fibrinogen levels increase with advancing pregnancy probably because of increase in estrogen levels.1 Fibrinogen decreases in PPH indicating derangements in coagulation pathways. Previous studies investigated serum fibrinogen and PPH to establish 2-4 or refute a prediction model between them 3, 5-7. The evidence for either hypothesis has remained weak because of conflicting findings. We questioned whether a pregnancy specific trigger/ hormonal disturbance influence both uterus tone and hemostasis of terminal pregnancy. For PPH subjects with atonic uterus, the fibrinogen levels will then be lowered predelivery. In subjects where PPH is not present, the fibrinogen levels will maintain a specific threshold level. We devised this comparative study between predelivery serum fibrinogen levels in vaginal delivery without PPH and with PPH. We hypothesized that predelivery serum Received: 10th September 2019. Accepted: 18th November 2019. Agarwal R, Jaiswal N, Kar R, Singh A, Srivastava H. Is serum fibrinogen an affirmative marker for vaginal delivery without PPH. The New Indian Journal of OBGYN. 2020; 6(2): 113-8. The New Indian Journal of OBGYN. 2020 (January-June); 6(2) fibrinogen be used as positive alert marker for maternal well being and a conception ending with ‘physiological’ blood loss rather than envisage a PPH. Methods The study was conducted in tertiary health care institution of a low income Indian subcontinent country in joint collaboration with Department of Obstetrics and Gynecology and Department of Biochemistry from November 2016 to April 2018. Institutional Ethical clearance and informed patient consent was obtained for the study. Sample size estimation In a study by Niepraschk-von Dollen et al, predelivery fibrinogen in severe PPH and without severe PPH, there was a standard deviation of fibrinogen level i.e. 0.75 g/L in control group and 0.8 g/L in severe PPH.2 Considering α = 5% and power = 80% to estimate a difference of 0.8 units in fibrinogen levels, minimum sample of 15 cases were required in each group.2 As prevalence of severe PPH in our hospital and other studies is around 3% of vaginal deliveries, for minimum 15 cases of severe PPH, we needed 500 subjects for the study.2 Inclusion and exclusion criteria For study enrolment, we included low-risk pregnant women between age group 18-40 years presenting with singleton pregnancy after 24 weeks of gestation. We excluded patients with possible obstetric risks (altered coagulation profile, hemoglobin <10 g/dl or thrombocytopenia (<105/mm3), hypertension, gestational diabetes and cholestasis. Predelivery blood samples were collected in these subjects on admission to the delivery suite when they presented with spontaneous labour and preserved for biochemical analysis. The subjects were then followed prospectively for spontaneous vaginal delivery. Patients requiring induction of delivery, instrumental or surgical delivery, with placental abruption or previa, with significant genital tract trauma or requiring manual removal of placenta were further excluded. A total of 453 subjects underwent spontaneous vaginal delivery and were eligible for fibrinogen estimation (figure 1). Due to limitation of financial resources, fibrinogen was finally estimated in 40 consecutive patients with PPH (rate limiting parameter) and equal number of non-PPH deliveries (random selection by computer generated numbers). 114 Blood loss estimation The blood loss at delivery was measured using an impermeable collection bag placed under the patient’s buttock and blood loss measurement was done by using a graduated jar (episiotomy was packed separately). Further, any sponges if used, were weighed separately using weighing scale and corresponding blood loss added. According to blood loss estimated, subjects were divided into three delivery groups (WHO definition)8: Non-PPH: Subjects with blood loss <500ml. Mild PPH: Cases with atonic PPH 500ml and 1000ml. Severe PPH: Cases with atonic PPH >1000ml with sign and symptoms of shock. All the subjects were followed up intensively and PPH was managed as per established hospital standard treatment protocols. Method of serum fibrinogen estimation 2 ml of blood collected in a plain vial was allowed to clot. It was then centrifuged at 5000 rpm for 5 minutes. The supernatant serum was divided into two aliquots in Eppendorf fuses and stored at -700C for further analysis. Estimation of serum fibrinogen was done using ELISA kit. Statistical analysis Normality of the data was ensured using Levene’s variance test. All quantitative parameters were expressed as mean ± standard deviation (SD). Non-PPH versus PPH fibrinogen levels and mild versus severe PPH were compared using unpaired student t test. A p ≤0.05 was considered significant. Fibrinogen levels and association with blood loss was determined using logistic re (...truncated)