Women’s Hospital, School of Medicine, Zhejiang University (WHZJU) has 460 maternity beds and serves many provinces of East China region. Approximately 20,000 births occur annually. As a first-class specialized hospital of obstetrics and gynecology in China and a nationally-known referral center, many of the pregnant women are complicated and high-risk.
We initiated the study in January 1st 2014 and continued until December 31st 2018, and we prospectively collected the data of women age 35 or older who gave birth at least 28 weeks of gestation at WHZJU. Women used anticoagulant or anti-platelet drugs before delivery or with incomplete clinical data were excluded from this study (Figure 1). The sample size required for the study was calculated according to the following formula:
In this formula, p0 indicated the incidence of VTE in D-dimer<5.545 mg /L group (0.96‰); p1 indicated the incidence of VTE in D-dimer≥5.545 mg /L group (6.8‰); p stood for the average value of p0 and p1; q=1-p. We set α=0.05 and β=0.10 (power=0.90); zα=1.96 and zβ=1.282, which represented for the boundary value of normal distribution. The estimated sample size was 2380. The sample size of this study was larger than the estimated sample size. All clinical variables were recorded, including age, body mass index (BMI), pregnancy times, parity, gestational weeks of delivery, fetal position, mode of delivery, fetal birth weight, pregnancy complications, postpartum hemorrhage and predictive biomarkers within postpartum 24 hours including D-dimer level, platelet counts and fibrinogen level. All biomarker values were obtained from the same laboratory affiliated to the hospital.
Clinical diagnosis of VTE
Imaging evidence was confirmed as the diagnostic criteria for VTE. Deep venous thrombosis (DVT) was diagnosed by upper and lower extremity venous color Doppler ultrasound and/or computed tomographic (CT) venography, and pulmonary embolism (PE) was diagnosed by CT pulmonary angiography.
Imaging examinations were required if the following conditions were present: (1) with suspicious symptoms of VTE, including pain or tenderness when move limbs, swelling of the limbs, measurement of inconsistencies in the circumference of the bilateral limbs, or unexplained dyspnea, chest pain or cough; or (2) with multiple high risk factors, and the clinician considered that the probability for VTE was great. Anticoagulation and antithrombotic therapy would be applied immediately when imaging examination indicated the diagnosis of VTE. All the VTE patients were told to follow up in the vascular department after discharge. Other women were followed up in the communities and would be accessed by vascular specialist in case of suspicious VTE symptoms (Figure 1).
We performed laboratory tests including platelet counts, fibrinogen level and D-dimer level. The detection of platelet counts was measured by impedance (XN9000; Sysmex, Kobe, Japan). The detection of fibrinogen level was measured by the solidification (Stago-R, Paris, France). The detection of D-dimer level was measured by the latex-enhanced immunoturbidimetry (Stago-R, Paris, France) (normal reference range for non-pregnant adults is less than 0.5 mg/L).
Data inputting and statistical analysis were performed in SPSS 22.0 (IBM Corporation, New York, USA). Continuous variables were described as means ± standard deviation. The continuous variables were compared by Student’s T test. The difference in the categorical variables was compared through Chi square test, Yate’s correction of continuity or Fisher’s exact test. Furthermore, to estimate the risk factors of VTE, the forward stepwise multiple logistic regression was performed. The associations between biomarkers and VTE were expressed as ROC curve analysis. Statistical significance was set at p<0.05.