Bleeding time and blood loss
. | Bleeding time, s . | . | Blood loss, nmol/mL . | . | ||
|---|---|---|---|---|---|---|
| Group . | Median . | Range . | Average . | SD . | ||
| Control | 45 | 0-954 | 7.6 | 7.0 | ||
| Hemophilia control | 1800*** vs A | 0-1800 | 159.5*** vs A | 137.2 | ||
| Hemophilia/rFVIIa, 1 mg/kg | 1685 | 575-1762 | 117.4 | 119.3 | ||
| Hemophilia/rFVIIa, 3 mg/kg | 649 | 0-1800 | 32.2*** vs B | 62.3 | ||
| Hemophilia/rFVIIa, 6 mg/kg | 487 | 75-1690 | 28.6** vs B | 38.7 | ||
| Hemophilia/rFVIIa, 10 mg/kg | 120*** vs B | 0-1637 | 11.7*** vs B | 11.6 | ||
| Hemophilia/FVIIaIIa, 1 mg/kg | 1083 | 0-1800 | 59.2** vs B | 92.9 | ||
| Hemophilia/FVIIaIIa, 3 mg/kg | 568 | 122-1671 | 8.6*** vs B | 2.0 | ||
| Hemophilia/K337A-FVIIaIIa, 1 mg/kg | 862 | 0-1800 | 45.7* vs B | 86.7 | ||
| Hemophilia/K337A-FVIIaIIa, 3 mg/kg | 35* vs B | 26-816 | 5.8** vs B | 0.3 | ||
| Hemophilia/M298Q-FVIIa, 1 mg/kg | 1334 | 0-1800 | 70.2* vs B | 112.1 | ||
| Hemophilia/M298Q-FVIIa, 3 mg/kg | 76*** vs B | 0-76 | 6.0*** vs B | 5.8 | ||
. | Bleeding time, s . | . | Blood loss, nmol/mL . | . | ||
|---|---|---|---|---|---|---|
| Group . | Median . | Range . | Average . | SD . | ||
| Control | 45 | 0-954 | 7.6 | 7.0 | ||
| Hemophilia control | 1800*** vs A | 0-1800 | 159.5*** vs A | 137.2 | ||
| Hemophilia/rFVIIa, 1 mg/kg | 1685 | 575-1762 | 117.4 | 119.3 | ||
| Hemophilia/rFVIIa, 3 mg/kg | 649 | 0-1800 | 32.2*** vs B | 62.3 | ||
| Hemophilia/rFVIIa, 6 mg/kg | 487 | 75-1690 | 28.6** vs B | 38.7 | ||
| Hemophilia/rFVIIa, 10 mg/kg | 120*** vs B | 0-1637 | 11.7*** vs B | 11.6 | ||
| Hemophilia/FVIIaIIa, 1 mg/kg | 1083 | 0-1800 | 59.2** vs B | 92.9 | ||
| Hemophilia/FVIIaIIa, 3 mg/kg | 568 | 122-1671 | 8.6*** vs B | 2.0 | ||
| Hemophilia/K337A-FVIIaIIa, 1 mg/kg | 862 | 0-1800 | 45.7* vs B | 86.7 | ||
| Hemophilia/K337A-FVIIaIIa, 3 mg/kg | 35* vs B | 26-816 | 5.8** vs B | 0.3 | ||
| Hemophilia/M298Q-FVIIa, 1 mg/kg | 1334 | 0-1800 | 70.2* vs B | 112.1 | ||
| Hemophilia/M298Q-FVIIa, 3 mg/kg | 76*** vs B | 0-76 | 6.0*** vs B | 5.8 | ||
Bleeding time: statistical significance was tested using nonparametric test, the Kruskal-Wallis test, and in case of overall P < .05, it was followed by Dunn posttest, comparing all groups with the hemophilia control group. The total bleeding time is defined as the sum of the duration of all the bleeding episodes from injection of drug until termination of the study. Observation time was 30 minutes. The bleeding time was increased in a highly significant way in the hemophilia control group compared with the normal control group (***P < .001). The bleeding time was significantly decreased after administration of 10 mg/kg rFVIIa (P < .001), 3 mg/kg K337-FVIIaIIa (*P < .05), and 3 mg M298Q-FVIIa (P < .001) compared with the hemophilia control group. The dose response of each of the rFVIIa compounds on the bleeding time was tested, and a highly significant dose response was observed for all compounds, rFVIIa (P < .0001), FVIIaIIa (P = .0015), K337A-FVIIaIIa (P = .0018), and M298Q-FVIIa (P < .0001). Blood loss: statistical significance was analyzed by ANOVA, and in case of overall P < .05 it was followed by Bonferronni multiple comparison test, comparing all groups to the hemophilia control group. The blood loss was significantly decreased after administration of 3 (P < .001), 6 (P < .001), and 10 (P < .001) mg/kg rFVIIa, 1 (**P < .01) and 3 (P < .001) mg/kg FVIIaIIa, 1 (P < .05) and 3 (P < .01) mg/kg K337A-FVIIaIIa, and 1 (P < .05) and 3 (P < .001) mg/kg M298Q-FVIIa compared with the hemophilia control. The dose responses of the FVIIa compounds were tested for the blood loss with a highly significant dose response for all compounds, rFVIIa (P < .0001), FVIIaIIa (P = .0044), K337A-FVIIaIIa (P = .0017), and M298Q-FVIIa (P < .0001).