TFPI resistance related to inherited or acquired protein S deficiency

Abstract

Background: Protein S (PS) is an essential component of the protein C pathway and PS deficiency can explain a poor response to activated protein C. It has recently been shown that PS also acts as a cofactor of Tissue Factor Pathway Inhibitor (TFPI).

Objectives: In the present study, we investigated whether PS deficiency could be responsible for a poor response to TFPI.

Patients/methods: Thirty-one patients with inherited PS deficiency, seven pregnant women and 36 controls were enrolled in the study. We measured the plasma response to added TFPI using a two-step diluted prothrombin time (dPT) assay. The response of the different plasmas to the anticoagulant activity of TFPI was expressed as TFPI Normalised Ratio (TFPI NR).

Results: The median TFPI NR was statistically significantly lower in patients with inherited PS deficiency (0.5) than in controls (1.0) (p<0.0001). It was statistically significantly lower in patients with type I inherited PS deficiency (0.47) compared to patients with type III inherited PS deficiency (0.58) (p=0.018). In contrast, it did not differ between patients with and without thrombosis. Median TFPI NR values were statistically significantly lower during pregnancy (0.54) than 3 months after delivery (0.71) (p=0.016). TFPI NR values correlated well with PS activity values (R(2)=0.681) whatever the nature of the PS deficiency.

Conclusions: Our findings confirm that PS deficiency results in a poor anticoagulant response to TFPI, demonstrating again the cofactor role of PS in TFPI activity.