Effect of recombinant factor VIIa (Novoseven) on thrombocytopenia-like conditions in vitro.
Recombinant factor VIIa (rFVIIa; NovoSeven, Novo Nordisk, Copenhagen, Denmark) may help to promote hemostasis in patients with thrombocytopenia. We used two in vitro models of thrombin generation to evaluate this effect. The reconstituted model contained tissue factor (TF)-expressing monocytes, unactivated platelets, isolated plasma coagulation proteins, and calcium. Platelet activation and thrombin generation were measured in timed aliquots. In the plasma-based model, thrombin generation was measured continuously after the addition of lipidated TF and calcium to platelet-rich plasma using a slowly cleaved fluorescent substrate. Thrombocytopenic conditions were mimicked by decreasing the platelet density. In both systems, a platelet density-dependent lowering of the thrombin-generation peak was observed. Addition of rFVIIa to samples with low platelet density (6700 to 10000/microL) increased the initial thrombin generation in both systems without normalizing thrombin-generation curves. The magnitude of the rFVIIa effect was most pronounced in the plasma-based model. Platelet activation was not significantly delayed at low platelet density in the reconstituted model. Addition of rFVIIa to samples with low platelet density caused faster platelet activation, most likely as a consequence of the increased initial thrombin generation. The data suggest that rFVIIa may help to achieve hemostasis at low platelet densities by increasing the initial thrombin generation, thereby compensating for low platelet number.
Kjalke
M
M
Haemostasis Biology, Novo Nordisk A/S, Måløv, Denmark.
Johannessen
M
M
Hedner
U
U
D001792:Blood Platelets / Q000187:drug effects / Q000378:metabolism; D003029:Coagulants / Q000494:pharmacology; D005167:Factor VII / Q000494:pharmacology*; D015942:Factor VIIa; D006801:Humans; D007700:Kinetics; D008070:Lipopolysaccharides / Q000494:pharmacology; D008954:Models, Biological; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology*; D013917:Thrombin / Q000096:biosynthesis / Q000187:drug effects; D013921:Thrombocytopenia / Q000188:drug therapy*; D013925:Thromboplastin / Q000187:drug effects / Q000378:metabolism
D003029:Coagulants; D008070:Lipopolysaccharides; D011994:Recombinant Proteins; D005167:Factor VII; D013925:Thromboplastin; C103587:recombinant FVIIa; D015942:Factor VIIa; D013917:Thrombin