Evaluation of the use of rotational thromboelastometry in the assessment of FXI deficency.

ABSTRACT

INTRODUCTION: The absence of a reliable clinical test to predict bleeding tendency leaves factor XI (FXI)-deficient individuals at risk of overtreatment or under treatment. AIM: To assess whether rotational thromboelastometry has value in detection of FXI deficiency and identification of bleeding tendency. METHODS: Thromboelastometry was measured in whole blood and platelet-rich plasma (PRP) samples containing corn trypsin inhibitor (CTI) from controls (n = 50) and FXI-deficient individuals (n = 93) at tissue factor (TF) 0.12 pm. The effect of tissue plasminogen activator was also assessed. For analysis, FXI-deficient individuals were divided into bleeders (n = 24) and non-bleeders (n = 44) based on experience of tonsillectomy and/or dental extraction prior to diagnosis. RESULTS: In whole blood, thromboelastometry distinguished those with major FXI deficiency (FXIC ≤ 15 IU dL-1 ) but not partial deficiency from control populations, but did not identify bleeding phenotype. In PRP, bleeders had significantly longer clot formation time [CFT; 434 ± 179 s vs. 277 ± 70 s (mean ± SD); P < 0.05] and smaller α angle [43.8 ± 9.5° vs. 52.4 ± 5.8° (mean ± SD); P < 0.05] compared to non-bleeders. However, these parameters were found to depend on multiple additional variables and on an individual basis, ROC analysis showed test specificity for bleeding phenotype identification to be only 38.5% at 100% sensitivity CFT (area under first derivative curve AUC = 0.8091, P = 0.0014), α angle (AUC = 0.7804, P = 0.006). CONCLUSION: Thromboelastometry in PRP with CTI samples triggered with TF 0.12 pm was able to distinguish between bleeders and non-bleeders in FXI deficiency, but poor specificity restricts its clinical application as a test to identify bleeding phenotype. Further technical advances to the assay may allow better discrimination.