To evaluate the
hemostatic effects of
NN1731 and
rFVIIa, an ex-vivo study in
hemophilia patients used the Hemodyne Hemostasis Analysis System (HAS) to measure platelet contractile force (PCF), clot elastic modulus (CEM), and force onset time (FOT), and the Haemoscope Thrombelastograph (TEG) to measure reaction time (R), kinetics time (K), and maximum amplitude (MA). Blood samples from 10 healthy volunteers and 10
Factor VIII-deficient patients of varying severity (mild, moderate, severe), were spiked with
rFVIIa and
NN1731 (both 0.64 and 1.28 microg/ml, respectively) and analyzed to characterize platelet function and clot kinetics. There was wide variability in the
rFVIIa response.
NN1731 had greater and more consistent effects on PCF, CEM, FOT, R, and K relative to
rFVIIa, in all
hemophilia groups. The lowest
NN1731 concentration (0.64 microg/ml) shortened R and FOT, and increased CEM and PCF more than
rFVIIa 1.28 microg/ml.
NN1731 normalized clotting parameters equivalent to values obtained in healthy volunteers. FOT and R were highly correlated (r = 0.96). No correlation was observed between CEM and MA.
NN1731 produced less variable, more pronounced and predictable ex-vivo
hemostatic effects on PCF, CEM, FOT, R and K than
rFVIIa in all
hemophilia groups. HAS and TEG assays provided similar estimates of FOT and R, however CEM appeared to be more sensitive than MA to changes in clot firmness.