The effect of tissue factor concentration on calibrated automated thrombography in the presence of inhibitor bypass agents

International Journal of Laboratory Hematology
Joost J van VeenM Makris

Abstract

Thrombin generation has been suggested as a method to monitor treatment with factor eight inhibitor bypassing activity (FEIBA) or recombinant FVIIa (rFVIIa). The sensitivity of the assay for individual coagulation factors is dependent on the tissue factor (TF) concentration. An inverse relation between the rFVIIa concentration needed to shorten the clotting time and TF concentration has been shown but the data on thrombin generation are inconsistent. Information on TF concentration in measurements with FEIBA is limited. We studied the influence of TF concentration (1 and 5 pM) on thrombin generation through spiking experiments with rFVIIa and/or FEIBA in the plasma of severe haemophilia A patients and after four and three treatment episodes, respectively, using the calibrated automated thrombin generation assay (CAT) in platelet poor plasma. Spiking with FEIBA showed a linear relation with the endogenous thrombin potential (ETP)/peak at 1 pM but substrate depletion at 5 pM. Spiking with rFVIIa showed a near linear dose-response relation with the ETP/peak at 1 pm but only a shortening of the initiation phase at 5 pM. Similar effects were present in post-treatment samples. FEIBA acted synergistically with rFVIIa. This suggest a r...Continue Reading

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Citations

Jul 6, 2012·Blood Reviews·Raed Al DieriH Coenraad Hemker
Nov 18, 2008·Thrombosis Research·Joost J van VeenMike Makris
Oct 2, 2012·International Journal of Laboratory Hematology·T-L KhooS Dunkley
Oct 15, 2013·Haemophilia : the Official Journal of the World Federation of Hemophilia·F KhanumD J Bowen
Feb 13, 2014·Haemophilia : the Official Journal of the World Federation of Hemophilia·J J van VeenM Makris
Dec 21, 2013·Haemophilia : the Official Journal of the World Federation of Hemophilia·H Luna-ZáizarA R Jaloma-Cruz
Jun 11, 2014·Journal of Thrombosis and Haemostasis : JTH·A M ShibekoM V Ovanesov
Apr 3, 2016·Haemophilia : the Official Journal of the World Federation of Hemophilia·N K JhaM V Ovanesov
Jun 7, 2011·Thrombosis Research·Alexander Y Mitrophanov, Jaques Reifman
Mar 8, 2012·Clinical and Applied Thrombosis/hemostasis : Official Journal of the International Academy of Clinical and Applied Thrombosis/Hemostasis·Yilmaz AyKaan Kavakli
Mar 19, 2019·Clinical and Applied Thrombosis/hemostasis : Official Journal of the International Academy of Clinical and Applied Thrombosis/Hemostasis·Ping ChenThomas S Kickler

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