| TFPI as a modifier of fibrinolysis and bleeding in FXI deficiency Stephanie Reitsma. |
Abstract
Factor XI (FXI) deficiency is associated with increased bleeding risk in some individuals. Neither FXI levels nor clinical assays are good predictors of this bleeding risk, leading to clinical under- or over treatment. Compared to controls, FXI-deficient bleeders have reduced clot formation, decreased fibrin network density, and increased susceptibility to fibrinolysis. Tissue factor pathway inhibitor (TFPI) has been implicated as a modifying factor in individuals with bleeding of unknown cause. We aimed to determine the potential of TFPI to modify bleeding risk in FXI-deficient individuals. We studied the effects of TFPI on thrombin generation, clotting and fibrinolysis in FXI-deficient plasma in vitro. Our data show that TFPI levels in plasma samples from FXI-deficient individuals correlate with parameters that distinguish FXI-deficient bleeders from non-bleeders. Plasma TFPI is increased in FXI-deficient bleeders. Coagulation and fibrinolysis parameters that differentiate FXI-deficient non-bleeders and bleeders are altered by plasma TFPI. Collectively, these data suggest plasma TFPI modifies bleeding risk in FXI-deficient individuals.
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