title: Is some better than none: are TEG and TGA profiles different in severe FVIII-deficient patients with inhibitors?
abstract: Severe factor VIII (FVIII)-deficient patients with and without FVIII inhibitors cannot be distinguished using FVIII levels. The FVIII assay is sensitive to detect factor levels below 1%. While severe FVIII-deficient, non-inhibitor patients have FVIII < 1%, they may retain unmeasurable residual factor activity. In contrast, inhibitor patients have a FVIII antibody that presumably fully eliminates FVIII activity. It is unknown whether thromboelastography (TEG) and thrombin generation assay (TGA) can differentiate between patients with FVIII < 1% with and without the presence of FVIII inhibitors. The primary objective was to discern whether TEG and TGA could differentiate between severe FVIII-deficient patients with and without the presence of FVIII inhibitors. A secondary objective was to correlate TEG and TGA to annualized bleeding rates. This observational study performed TEG and TGA in healthy volunteers (N = 15), severe FVIII-deficient (N = 15) and severe FVIII-deficient patients with inhibitors (N = 15). Kaolin-activated TEG was better at differentiating reaction time (31.3 vs. 120 min respectively, P = 0.004) and kinetics time (6.1 vs. 23.1 min respectively, P = 0.028) between the non-inhibitor and inhibitor patients. TEG activated by tissue factor in plasma-containing corn trypsin inhibitor failed to differentiate groups. The TGA failed to differentiate peak thrombin, endogenous thrombin potential and lag time between groups. There was no correlation between TEG and TGA with annualized bleeding rates. Kaolin-activated TEG, but not TGA, differentiated between severe FVIII-deficient patients with and without inhibitors. These assays did not find a correlation to annualized bleeding rate.
authors.affiliation: Division of Hematology/Oncology, Hemostasis and Thrombosis Center, Children's Hospital Los Angeles and University of Southern California Keck School of Medicine, Los Angeles, CA, USA.
authors.forename: V
authors.initials: V
authors.lastname: Salinas
authors.affiliation: Division of Hematology/Oncology, Hemostasis and Thrombosis Center, Children's Hospital Los Angeles and University of Southern California Keck School of Medicine, Los Angeles, CA, USA.
authors.forename: R
authors.initials: R
authors.lastname: Carmona
authors.affiliation: Coagulation Advancement Laboratory, Department of Pharmacotherapy and Outcomes Science, Virginia Commonwealth University, Richmond, VA, USA.|Faculty of Pharmacy, Department of Clinical Pharmacy, Cairo University, Giza, Egypt.
authors.forename: B M
authors.initials: BM
authors.lastname: Mohammed
authors.affiliation: Coagulation Advancement Laboratory, Department of Pharmacotherapy and Outcomes Science, Virginia Commonwealth University, Richmond, VA, USA.
authors.forename: E J
authors.initials: EJ
authors.lastname: Martin
authors.affiliation: Coagulation Advancement Laboratory, Department of Pharmacotherapy and Outcomes Science, Virginia Commonwealth University, Richmond, VA, USA.
authors.forename: D F
authors.initials: DF
authors.lastname: Brophy
authors.affiliation: Division of Hematology/Oncology, Hemostasis and Thrombosis Center, Children's Hospital Los Angeles and University of Southern California Keck School of Medicine, Los Angeles, CA, USA.
authors.forename: G
authors.initials: G
authors.lastname: Young
mesh_terms: D000293:Adolescent; D000328:Adult; D019774:Blood Coagulation Factor Inhibitors / Q000097:blood / Q000276:immunology*; D001780:Blood Coagulation Tests / Q000379:methods; D002648:Child; D002675:Child, Preschool; D005169:Factor VIII / Q000276:immunology*; D006467:Hemophilia A / Q000097:blood / Q000175:diagnosis* / Q000188:drug therapy / Q000276:immunology*; D006801:Humans; D007518:Isoantibodies / Q000097:blood / Q000276:immunology; D008297:Male; D012720:Severity of Illness Index; D013916:Thrombelastography; D055815:Young Adult
chemical_list: D019774:Blood Coagulation Factor Inhibitors; D007518:Isoantibodies; D005169:Factor VIII
keywords: haemophilia; inhibitors; thrombin generation; thromboelastography