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

• Published in: Haemophilia : the official journal of the World Federation of Hemophilia 2017-05, Vol.23 (3), p.449-457
• Main Authors: Pike, G. N., Cumming, A. M., Thachil, J., Hay, C. R. M., Bolton‐Maggs, P. H. B., Burthem, J.
• Format: Article
• Language: English
• Subjects: Adult; Aged; Bleeding; bleeding disorder; blood coagulation; Coagulation factors; factor XI; factor XI deficiency; Factor XI Deficiency - blood; Factor XI Deficiency - complications; Factor XI Deficiency - diagnosis; Female; fibrinolysis; Genotype & phenotype; Hemorrhage - complications; Humans; Male; Middle Aged; Risk Assessment; Rotation; t-Plasminogen activator; Thrombelastography; thromboelastometry; Tissue factor; Trypsin; Young Adult
• ISSN: 1351-8216; 1365-2516
• DOI: 10.1111/hae.13136

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 (FXI:C ≤ 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.