The Department of Obstetrics and Gynaecology, University of Melbourne, Australia; Mercy Perinatal, Mercy Hospital for Women, Victoria, Australia.
The Department of Obstetrics and Gynaecology, University of Melbourne, Australia; Mercy Perinatal, Mercy Hospital for Women, Victoria, Australia; Translational Obstetrics Group, Mercy Hospital for Women, 163 Studley Road, Heidelberg, 3084, Victoria, Australia.
Placenta. 2021 Feb;105:32-40. doi: 10.1016/j.placenta.2021.01.018. Epub 2021 Jan 22.
Tissue Factor Pathway Inhibitor (TFPI) is a part of the extrinsic coagulation pathway, and highly expressed in the placenta. We aimed to assess its potential as a preeclampsia biomarker.
Maternal plasma was prospectively collected at 36 weeks' gestation. Circulating TFPI was measured in a nested case-control group (39 women who developed preeclampsia, 98 controls), before being measured in a larger independent cohort along with Placental Growth Factor (PlGF; 41 who developed preeclampsia, 954 controls). Circulating TFPI was then measured in women with underlying vascular disease, and also assessed in the plasma and placentas from women with preterm preeclampsia (delivered at <34 weeks).
Circulating TFPI was significantly increased in women destined to develop preeclampsia in the case-control study, a finding that validated in Cohort 2, with median TFPI in the preeclampsia group being 42.3 ng/ml (IQR 30-51 ng/ml) compared to 30 ng/ml (IQR 23.1-38.6 ng/ml) in controls (p < 0.0001). The area under the receiver operator characteristic curve (AUC) was 0.70. PlGF was significantly reduced in the preeclampsia group, and a ratio of TFPI/PlGF had an improved AUC of 0.78. In women with underlying vascular disease who were later diagnosed with early onset preeclampsia, circulating TFPI was significantly increased with a 0.29 (95% CI 0.13-0.44) increase in logTFPI (adjusted for gestation and hypertensive status). Circulating and placental TFPI were significantly increased in women with preterm preeclampsia.
Circulating TFPI is increased in women preceding diagnosis of preeclampsia (at 36 weeks) and in women with preterm disease. TFPI may beneficially contribute to a multi-marker blood test to predict preeclampsia.
组织因子途径抑制剂（TFPI）是外源性凝血途径的一部分，在胎盘组织中高度表达。我们旨在评估其作为子痫前期生物标志物的潜力。
前瞻性地在 36 孕周时采集母体血浆。在巢式病例对照研究中（39 例发生子痫前期的妇女，98 例对照）测量循环 TFPI，然后在更大的独立队列中与胎盘生长因子（PlGF；41 例发生子痫前期，954 例对照）一起测量。然后在患有潜在血管疾病的妇女中测量循环 TFPI，并评估在早产子痫前期（<34 周分娩）妇女的血浆和胎盘组织中的 TFPI。
在病例对照研究中，注定发生子痫前期的妇女循环 TFPI 显著升高，该结果在队列 2 中得到验证，子痫前期组 TFPI 的中位数为 42.3ng/ml（IQR 30-51ng/ml），而对照组为 30ng/ml（IQR 23.1-38.6ng/ml）（p<0.0001）。接受者操作特征曲线（ROC）下的面积（AUC）为 0.70。子痫前期组 PlGF 明显降低，TFPI/PlGF 比值的 AUC 为 0.78。在后来被诊断为早发型子痫前期的患有潜在血管疾病的妇女中，循环 TFPI 显著增加，logTFPI 增加 0.29（95%CI 0.13-0.44）（调整孕周和高血压状态）。早产子痫前期妇女的循环和胎盘 TFPI 均显著升高。
在子痫前期诊断前（36 周）和早产疾病的妇女中，循环 TFPI 增加。TFPI 可能有助于预测子痫前期的多标志物血液检测。
