title: Evaluation of the use of rotational thromboelastometry in the assessment of FXI deficency.
abstract: BACKGROUND
  The absence of a reliable clinical test to predict bleeding tendency leaves factor XI (FXI)-deficient individuals at risk of overtreatment or under treatment.
  
  
  OBJECTIVE
  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).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Haematology, Manchester Royal Infirmary, Central Manchester University Hospital NHS Trust, Manchester, UK.|Institute of Cancer Sciences, The University of Manchester, Manchester, UK.
authors.forename: G N
authors.initials: GN
authors.lastname: Pike
authors.affiliation: Haematology Molecular Diagnostics Centre, Manchester Royal Infirmary, Central Manchester University Hospital NHS Trust, Manchester, UK.
authors.forename: A M
authors.initials: AM
authors.lastname: Cumming
authors.affiliation: Department of Haematology, Manchester Royal Infirmary, Central Manchester University Hospital NHS Trust, Manchester, UK.
authors.forename: J
authors.initials: J
authors.lastname: Thachil
authors.affiliation: Department of Haematology, Manchester Royal Infirmary, Central Manchester University Hospital NHS Trust, Manchester, UK.|Haematology Molecular Diagnostics Centre, Manchester Royal Infirmary, Central Manchester University Hospital NHS Trust, Manchester, UK.
authors.forename: C R M
authors.initials: CRM
authors.lastname: Hay
authors.affiliation: The University of Manchester, Manchester, UK.|SHOT Office, Manchester Blood Centre, Manchester, UK.
authors.forename: P H B
authors.initials: PHB
authors.lastname: Bolton-Maggs
authors.affiliation: Department of Haematology, Manchester Royal Infirmary, Central Manchester University Hospital NHS Trust, Manchester, UK.|Institute of Cancer Sciences, The University of Manchester, Manchester, UK.
authors.forename: J
authors.initials: J
authors.lastname: Burthem
mesh_terms: D000328:Adult; D000368:Aged; D005173:Factor XI Deficiency / Q000097:blood / Q000150:complications / Q000175:diagnosis*; D005260:Female; D006470:Hemorrhage / Q000150:complications; D006801:Humans; D008297:Male; D008875:Middle Aged; D018570:Risk Assessment; D012399:Rotation; D013916:Thrombelastography; D055815:Young Adult
keywords: bleeding disorder; blood coagulation; factor XI; factor XI deficiency; fibrinolysis; thromboelastometry