Funding period: 01.03.2019 – 29.02.2020
Thrombin generation (TG) assays are emerging as tools for assessing individual risk for thrombosis or bleeding. We have recently shown that investigating the procoagulant activity in a platelet dependent manner is superior to a condition in absence of platelets for assessment of an individual risk for cardiovascular disease. Tissue factor pathway inhibitor (TFPI), an endothelial and platelet derived protein, is the main inhibitor of the extrinsic coagulation pathway and therefore an important modulator of the coagulation inhibition. TFPI mainly originates from vascular endothelial cells and the majority of TFPI (80%) remains associated with the endothelium (TFPI-β). From the circulating form, 10-20% is active full-length form known as TFPI-α, whereas the remaining TFPI mainly circulates in plasma as carboxy-terminally truncated and lipid-bound. In addition, platelets contain a pool of TFPI that is exclusively full length TFPI-α, released after platelet activation. The activity of TFPI-α in plasma by the TG assay in a population-based setting has not been investigated so far. Our preliminary data suggest that modulation of TG by addition of anti-TFPI-α antibody could bring additional information for individuals’ cardiovascular risk. Furthermore, investigating the circulating total and full-length TFPI-α of the same individuals would help to further understand its correlations to the functional assay by TG performed in presence and absence of anti TFPI-α antibody. In the present translational research project we will investigate, in a representative subsample of the Gutenberg Health Study, the contribution of α-TFPI in the TG measured in platelet free plasma (PFP) with subjects’ cardiovascular profile. In addition, in the same study subjects, we will assess plasma endothelial and platelet activation biomarkers and the relation to cardiovascular profile. Finally, we will analyze the association between TG parameters in different experimental conditions (platelet rich plasma, PFP, PFP + anti TFPI-α ab) and the soluble endothelial and platelet biomarkers, particularly in respect to cardiovascular risk profile.