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Evaluation of the overall haemostatic effect of recombinant factor VIIa by measuring thrombin generation and stability of fibrin clots
Author(s) -
DARGAUD Y.,
PREVOST C.,
LIENHART A.,
CLAUDE BORDET J.,
NEGRIER C.
Publication year - 2011
Publication title -
haemophilia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.213
H-Index - 92
eISSN - 1365-2516
pISSN - 1351-8216
DOI - 10.1111/j.1365-2516.2011.02526.x
Subject(s) - thromboelastography , fibrin , fibrinolysis , medicine , recombinant factor viia , thrombin , factor xiii , recombinant dna , plasminogen activator , coagulation , thrombelastography , tissue plasminogen activator , tissue factor , thrombin generation , biomedical engineering , pharmacology , immunology , surgery , chemistry , biochemistry , platelet , gene
Summary. It has been reported that thrombin generation test (TGT) may be a useful tool to monitor recombinant factor VIIa (rFVIIa). However, TGT does not reflect the stability of fibrin clot and its resistance to fibrinolysis which are crucial. Using whole‐blood thromboelastography (TEG) and tissue plasminogen activator (tPA), we developed an in‐vitro model to assess fibrin clot stability. Fibrin fibres were thicker in haemophiliacs compared with controls ( P < 0.0001). After addition of rFVIIa 90 μg kg −1 , the diameter of fibrin fibres was dramatically decreased ( P = 0.006). TEG‐tPA assay showed a dose‐dependent improvement of clot stability in the presence of rFVIIa. These data demonstrate a significant correlation between fibrin clot structure and its stability ( P = 0.001). We also showed a correlation between thrombin generating capacity and clot resistance to fibrinolysis. Despite this overall correlation, a relatively large spreading around a general trend was observed, suggesting that the two assays bring complementary information on the haemostatic effect of rFVIIa.