Evaluation of thrombin generation assay in factor XI deficiency.

Factor XI (FXI) deficiency is characterized by a lack of correlation between FXI plasma levels and the occurrence of hemorrhagic events. The main objective of our study was to determine whether thrombin generation assay (TGA) could be used to assess the hemorrhagic phenotype of patients with FXI deficiency. All patients had confirmed laboratory measurement of FXI < 50% in two plasma samples. Relevant bleeding history was evaluated by a senior physician. TGA was performed with Calibrated Automated Thrombography, in platelet poor plasma, from patients and healthy controls. The assay was performed with PPP low reagent (1 pM of human tissue factor). Seventy-six patients with FXI deficiency were included between 2011 and 2020. Among them, eight patients had severe deficiency (FXI < 15%). Mean age was 34 years [range: 9-77]. Endogenous thrombin potential (ETP) was significantly lower in patients with FXI deficiency and bleeding (573 nM·min [225-1214]) or no bleeding (732 nM·min [222-1435]), compared to healthy controls (1184 nM·min [933-1518]). No difference was observed for ETP and peak between patients with FXI deficiency and bleeding and patients with FXI deficiency and no bleeding. No difference was observed for ETP (923 nM·min [377-1497] vs 1063 nM·min [252-2529]), peak (82 nM [28-154] vs 131 nM [20-330]) or velocity (13.7 nM/min [3.6-29.6] vs 26.5 nM/min [2.5-90]) in women with (n = 4) and without history (n = 17) of post-partum bleeding. No difference of thrombin generation was observed in pregnant women with FXI deficiency (ETP: 1395 nM·min [351-2529]; peak: 154 nM [26-330]; velocity: 29.6 nM/min [4.1-90.0]), compared to healthy controls and a control group of healthy pregnant women. In conclusion, under our experimental condition, a non-significant decrease of thrombin generation was observed in plasma samples of patients with FXI deficiency and bleeding. Our results suggest an increase of coagulation parameters during pregnancy in women with FXI deficiency. A larger sample size or other experimental conditions are required to evaluate the use of TGA in FXI deficiency.

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