Acute release of tissue factor pathway inhibitor after in vivo thrombin generation in baboons

Tissue pathway inhibitor (TFPI), the major downregulator of the procoagulan t activity of tissue factor (TF), is synthesised by endothelial cells (EC) and acutely released in vitro after thrombin stimulation. Expression of TF on EC and subsequent thrombin generation occurs in vivo during sepsis or ma lignancy, inducing disseminated intravascular coagulation (DIC). The presen t study investigates the changes in plasma TFPI in relation to markers of i n vivo thrombin generation induced by injection of factor Xa (FXa)/phosphol ipids in baboons at dosages leading to partial (48%) or complete fibrinogen depletion. The plasma concentrations of thrombin-antithrombin III (TAT) an d fibrinopeptide A (FpA), as markers of ill vivo generation of thrombin, we re strongly enhanced after injection of FXa/phospholipids. TFPI levels, whe ther measured as antigen or activity, increased significantly in both treat ment groups within few minutes, and were dependent on the dose of FXa/phosp holipids. Significant positive correlations between plasma levels of TFPI a nd of TAT or FpA were observed. Altogether, our results indicate that exper imentally induced in vivo generation of thrombin causes the acute release o f TFPI, highlighting a possible novel function of thrombin in downregulatio n of the coagulation process, potentially relevant for the: outcome of DIC.