Evaluation of thrombin generation assay in factor XI deficiency

Area of Science:

• Hematology
• Coagulation Science
• Clinical Diagnostics

Background:

• Factor XI (FXI) deficiency presents a disconnect between FXI plasma levels and the manifestation of hemorrhagic events.
• The clinical utility of assessing FXI levels for predicting bleeding risk remains uncertain.

Purpose of the Study:

• To investigate the efficacy of thrombin generation assay (TGA) in evaluating the hemorrhagic phenotype in patients with Factor XI deficiency.
• To determine if TGA can serve as a reliable diagnostic tool for predicting bleeding complications in FXI deficiency.

Main Methods:

• Seventy-six patients with FXI deficiency (FXI < 50%) and confirmed bleeding history were analyzed.
• Thrombin generation assay (TGA) was performed using Calibrated Automated Thrombography on platelet-poor plasma.
• Assays utilized low tissue factor (1 pM) to assess endogenous thrombin generation potential (ETP).

Main Results:

• Endogenous thrombin potential (ETP) was significantly lower in FXI-deficient patients (with or without bleeding) compared to healthy controls.
• No significant differences in ETP or peak thrombin were observed between FXI-deficient patients with and without bleeding.
• Thrombin generation parameters did not differ in women with FXI deficiency experiencing postpartum bleeding or in pregnant women with FXI deficiency.

Conclusions:

• Under the tested experimental conditions, TGA did not show a significant decrease in thrombin generation in FXI-deficient patients with bleeding.
• Coagulation parameters may increase during pregnancy in women with FXI deficiency.
• Larger sample sizes or alternative experimental conditions are necessary to validate TGA's utility in FXI deficiency.