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TFPI resistance related to inherited or acquired protein S deficiency

Brigitte Tardy-Poncet1, Michèle Piot, Dominique Brunet

  • 1Université de Lyon, F-42023, Saint-Etienne, France. brigitte.tardy@chu-st-etienne.fr

Thrombosis Research
|October 20, 2012
PubMed

Insights

Protein S (PS) deficiency impairs the anticoagulant response to Tissue Factor Pathway Inhibitor (TFPI). This study confirms PS acts as a cofactor for TFPI, impacting its effectiveness.

Area of Science:

  • Hematology
  • Coagulation Science

Background:

  • Protein S (PS) is crucial in the protein C pathway and acts as a cofactor for Tissue Factor Pathway Inhibitor (TFPI).
  • PS deficiency can lead to a diminished response to activated protein C.

Purpose of the Study:

  • To investigate if PS deficiency is associated with a poor anticoagulant response to TFPI.
  • To further elucidate the role of PS as a cofactor in TFPI activity.

Main Methods:

  • Plasma samples from 31 patients with inherited PS deficiency, 7 pregnant women, and 36 controls were analyzed.
  • The response to TFPI was measured using a two-step diluted prothrombin time (dPT) assay, quantifying TFPI Normalized Ratio (TFPI NR).

Main Results:

  • Patients with PS deficiency exhibited significantly lower TFPI NR compared to controls (0.5 vs. 1.0, p<0.0001).
  • TFPI NR was lower in type I PS deficiency than type III and was reduced during pregnancy.
  • TFPI NR values strongly correlated with PS activity levels (R²=0.681).

Conclusions:

  • PS deficiency results in a significantly reduced anticoagulant response to TFPI.
  • This confirms the essential cofactor role of Protein S in TFPI-mediated anticoagulation.
Abstract

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