Circulating Tissue Factor Pathway Inhibitor (TFPI) is increased preceding preeclampsia diagnosis and in established preeclampsia. (February 2021)

• Record Type: Journal Article
• Authors: MacDonald, Teresa M.; Tong, Stephen; Myers, Jenny; Cannon, Ping; Nguyen, Tuong-Vi; Keenan, Emerson; Murray, Elizabeth; Harper, Alesia; Pritchard, Natasha; Hannan, Natalie J.; Dane, Kirsten M.; Middleton, Anna L.; Kyritsis, Valerie P.; Walker, Susan P.; Kaitu'u-Lino, Tu'uhevaha J.
• Is Part Of: Placenta. Volume 105(2021)
• Page Start: 32
• Page End: 40
• Publication Date: 2021-02
• Subjects: Preeclampsia -- Tissue factor pathway inhibitor (TFPI) -- Biomarker -- Prediction; Placenta -- Periodicals; Reproduction -- Periodicals; Placenta -- Periodicals; Placenta -- Périodiques; Reproduction -- Périodiques; 612.63
• DOI: 10.1016/j.placenta.2021.01.018
• Languages: English
• ISSNs: 0143-4004

Abstract

Abstract: Introduction: 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. Methods: 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). Results: 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. Discussion: 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. Highlights: Plasma TFPI is increased in women destined to develop preeclampsia. A ratio of TFPI/PlGF increases discrimination over TFPI alone. Plasma TFPI was increased in women with underlying vascular disease destined to develop early onset preeclampsia. Plasma and placental TFPI is elevated in preterm preeclampsia (<34 weeks' gestation). TFPI may beneficially contribute to a multi-marker blood test to predict preeclampsia.