Factor XI (FXI) deficiency is a rare
bleeding disorder. Most patients with FXI deficiency are mild bleeders but certain patients with similar FXI activity exhibit different
bleeding phenotype. Routine laboratory assays do not help physicians to estimate the individual
bleeding risk in these patients.
Thrombin generation test (TGT) is a more comprehensive, global function test of the clotting system. We investigated whether or not the
bleeding tendency of patients with FXI deficiency is correlated with features of the TGT. Twenty-four patients with FXI deficiency were divided in two groups: (i) severe bleeders (n = 9) and (ii) mild or non-bleeders (n = 15). All severe bleeders had a personal history of surgery-related severe
bleeding.
Thrombin generation (TG) was measured in platelet-rich plasma (PRP) using a low concentration of
tissue factor 0.5 pm. In patients exhibiting severe
bleeding tendency, independently of their FXI level, a dramatically impaired TG was observed. For example, despite a low plasma FXI = 1 IU dl(-1), a clinically non-
bleeding individual exhibited normal TG results whereas another patient with severe
bleeding history and FXI = 40 IU dl(-1) had a very low TG capacity. Low velocity and delayed TG were the main parameters suggesting a higher
bleeding risk.
DNA analysis of patients reported eight novel mutations of the FXI gene but neither mutation location nor secretion or not of the variant correlated with the
bleeding tendency. The results of this study suggest that TG measurement in PRP may be a useful tool to predict
bleeding risk in FXI deficiency and should be studied further in larger prospective clinical studies.