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Recombinant human factor VIIa (rFVIIa) can activate factor FIX on activated platelets
Author(s) -
Gabriel D. A.,
Li X.,
Monroe D. M.,
Roberts H. R.
Publication year - 2004
Publication title -
journal of thrombosis and haemostasis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.947
H-Index - 178
eISSN - 1538-7836
pISSN - 1538-7933
DOI - 10.1111/j.1538-7836.2004.01015.x
Subject(s) - platelet , chemistry , recombinant factor viia , tissue factor , thrombin , recombinant dna , factor ixa , platelet activation , pharmacology , factor viia , factor x , coagulation , biophysics , biochemistry , immunology , medicine , anesthesia , biology , gene
Summary. The studies reported here show that factor (F)VIIa can activate factor (F)IX on activated platelets in the absence of tissue factor. Both FIX and FIXa bind to the activated platelet surface with a K d of 8 nM and 2 nM, respectively. With factor (F)VIIIa, FIXa binds more tightly to platelets (K d 0.6 nM). At rFVIIa concentrations < 100 n m , no direct binding to the activated platelet surface can be detected with electrophoretic light scattering. However, in the presence of FIX, rFVIIa binding to platelets at concentrations as low as 10 n m rFVIIa can be detected. This is reflected by a decrease in the FIX K d from 8 to 1.6 nM. When rFVIIa is added to activated platelets in the presence of both FIX and FVIIIa, the K d for FIX decreases to 0.6, suggesting that rFVIIa activates FIX on the surface of activated platelets in the absence of tissue factor. The activation of FIX by FVIIa on activated platelets can also be demonstrated by a functional assay for FIXa. These data show that pharmacological doses of rFVIIa result in the direct activation of FIX by rFVIIa to form additional tenase complexes ultimately resulting in improved thrombin generation. These results may explain, at least in part, the mechanism of action of rFVIIa in hemorrhagic conditions seen in otherwise normal patients who develop an acquired coagulopathy due to trauma, surgery or a variety of other events in which rFVIIa has been found to be effective.