title: Comparison of kaolin and tissue factor activated thromboelastography in haemophilia.
abstract: A limitation of bypassing agent therapy for haemophilia patients with inhibitors is the absence of a laboratory assay, which predicts the clinical response to treatment. Recent investigations have demonstrated the potential for thromboelastography to assess the effects of bypassing agent therapy in this patient population. While tissue factor activation has been used in several prior studies, a recent multicentre study failed to demonstrate an expected concentration-response effect of rFVIIa and called into question the tissue factor activation methods that have been employed. A comparison of kaolin to two concentrations of tissue factor as the activation method for thromboelastography was investigated in patients with haemophilia. We performed kaolin and tissue factor activated thromboelastography on blood from inhibitor and non-inhibitor patients with and without addition of rFVIIa and rFVIII. The results demonstrate that kaolin leads to a longer R, K and angle than the higher dilution of tissue factor (1:17 000) at baseline (no factor) and after addition of rFVIIa for both the inhibitor and non-inhibitor patients. Kaolin led to a longer R and K in comparison to a low dilution of tissue factor (1:42 000) following the addition of rFVIIa in the inhibitor patients. The longer R and K allows for better discrimination of the effects of rFVIIa thus making kaolin the most sensitive activation method in this setting. Thus kaolin activated thromboelastography should be considered an effective, perhaps the most effective, activator when utilizing thromboelastography to assess the effects of rFVIIa in haemophilia patients with inhibitors.
authors.affiliation: Division of Hematology/Oncology, Children's Hospital Los Angeles, University of Southern California Keck School of Medicine, Los Angeles, CA 90027, USA. gyoung@chla.usc.edu
authors.forename: G
authors.initials: G
authors.lastname: Young
authors.forename: R
authors.initials: R
authors.lastname: Zhang
authors.forename: R
authors.initials: R
authors.lastname: Miller
authors.forename: D
authors.initials: D
authors.lastname: Yassin
authors.forename: D J
authors.initials: DJ
authors.lastname: Nugent
mesh_terms: D000293:Adolescent; D000328:Adult; D001777:Blood Coagulation / Q000187:drug effects; D004347:Drug Interactions; D005169:Factor VIII / Q000494:pharmacology*; D015942:Factor VIIa / Q000494:pharmacology*; D006467:Hemophilia A / Q000097:blood / Q000188:drug therapy*; D006801:Humans; D007616:Kaolin / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D011994:Recombinant Proteins / Q000494:pharmacology; D013916:Thrombelastography / Q000379:methods*; D055815:Young Adult
chemical_list: D011994:Recombinant Proteins; D007616:Kaolin; D005169:Factor VIII; C103587:recombinant FVIIa; D015942:Factor VIIa