Elevated plasma TFPI activity causes attenuated TF-dependent thrombin generation in early onset preeclampsia

Thromb Haemost. 2017 Jul 26;117(8):1549-1557. doi: 10.1160/TH16-12-0949. Epub 2017 Jun 1.

Abstract

Early onset preeclampsia (EOP) is a pregnancy-specific proinflammatory disorder that is characterised by competing thrombotic and bleeding risks. It was the aim of this study to characterise thrombin generation, a major determinant of thrombotic and bleeding risk, in order to better understand the haemostatic balance in patients with EOP. Patients with EOP were recruited at the Rotunda Hospital, Dublin. Twenty-six cases of EOP were recruited over a 21-month period, out of 15,299 deliveries at the Rotunda. Blood samples were collected into sodium citrate plus corn trypsin inhibitor anticoagulated vacutainers, platelet-poor plasma was prepared, and calibrated automated thrombography was used to assess thrombin generation. Results were compared to age and sex-matched non-pregnant controls (n=13) and age- and gestation-matched pregnant controls (n=20). The rate and extent of thrombin generation triggered by low-dose tissue factor (TF) was significantly reduced in patients with EOP compared to pregnant controls, most significantly in cases of severe EOP. EOP patients displayed a trend towards an increased response to endogenous activated protein C and thrombomodulin relative to pregnant controls. Plasma tissue factor pathway inhibitor (TFPI) activity was increased in EOP patients. Inhibition of TFPI abolished the attenuation of thrombin generation stimulated by low-dose TF. In conclusion, patients with EOP are characterised by an attenuated coagulation response characterised by reduced thrombin generation stimulated by low-dose TF and elevated plasma TFPI activity. These changes in coagulation may modulate thrombotic risk and bleeding risk in patients with EOP.

Keywords: Pregnancy; tissue factor; tissue factor pathway inhibitor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Biomarkers / blood
  • Blood Coagulation Tests
  • Blood Coagulation*
  • Carboxypeptidase B2 / blood*
  • Case-Control Studies
  • Female
  • Gestational Age
  • Hemorrhage / blood
  • Hemorrhage / diagnosis
  • Hemorrhage / enzymology*
  • Humans
  • Ireland
  • Pre-Eclampsia / blood
  • Pre-Eclampsia / diagnosis
  • Pre-Eclampsia / enzymology*
  • Pregnancy
  • Prognosis
  • Protein C / metabolism
  • Protein S / metabolism
  • Risk Factors
  • Thrombin / metabolism*
  • Thrombomodulin / blood
  • Thromboplastin / metabolism*
  • Thrombosis / blood
  • Thrombosis / diagnosis
  • Thrombosis / enzymology*
  • Up-Regulation

Substances

  • Biomarkers
  • Protein C
  • Protein S
  • THBD protein, human
  • Thrombomodulin
  • Thromboplastin
  • CPB2 protein, human
  • Carboxypeptidase B2
  • Thrombin