Table 3.
Overview of the effect of diminishing fibrinolysis in hemophilia A (HA) animal models subjected to the tail vein transection (TVT) bleeding model as assessed by blood loss, bleeding time, and spontaneous bleeds; total blood loss, bleeding time, spontaneous bleeds and tranexamic acid (TXA) plasma concentration as observed in the TVT model
| Figure | Study | Treatment group | Blood loss (nmol of Hgb) | Bleeding time (min) | Spontaneous bleeds | TXA exposure (μg mL−1) |
|---|---|---|---|---|---|---|
| 2 | FVIII−/− rats | Vehicle | 37 721 ± 3898 | 31.5 ± 1.4 | 1.6 ± 0.4 | 0 |
| TXA | 44 114 ± 5914 | 35.2 ± 0.9 | 1.3 ± 0.26 | 228.7 ± 34 | ||
| rFVIIa | 18 821 ± 3108 | 21.6 ± 4.0 | 1.7 ± 0.87 | 0 | ||
| rFVIIa and TXA | 25 926 ± 4401 | 29.3 ± 2.6 | 1.4 ± 0.31 | 161.5 ± 18.6 | ||
| WT | 10 939 ± 2424 | 6.3 ± 0.4 | 0.09 ± 0.09 | 0 | ||
| 3A-D | FVIII−/− mice | Vehicle | 4745 ± 545.9 | 23.3 ± 2.8 | 1.06 ± 0.14 | 0 |
| TXA | 4115 ± 439 | 23.3 ± 2.1 | 0.87 ± 0.19 | 104.9 ± 9.57 | ||
| rFVIIa | 3449 ± 599 | 19.9 ± 2.8 | 0.8 ± 0.14 | 0 | ||
| rFVIIa and TXA | 1500 ± 419 | 11.2 ± 2.5 | 0.73 ± 0.28 | 118.9 ± 11.5 | ||
| WT | 366 ± 85 | 3.7 ± 0.4 | 0 ± 0 | 0 | ||
| 3E-H | FVIII−/− mice | Vehicle | 5326 ± 546 | 20.56 ± 1.8 | 1.33 ± 0.43 | 0 |
| TXA | 4355 ± 628 | 20.28 ± 2.7 | 1 ± 0.21 | 150 ± 37.5 | ||
| rFVIII | 3740 ± 724 | 16.7 ± 2.9 | 1.25 ± 0.35 | 0 | ||
| rFVIII and TXA | 2322 ± 600 | 12.8 ± 2.7 | 1.25 ± 0.33 | 139.9 ± 15.2 | ||
| WT | 657 ± 127 | 4.9 ± 0.4 | 0 ± 0 | 0 | ||
| 4 | C57Bl/6 | Vehicle | 6064 ± 967 | 29 ± 1.1 | 0.75 ± 0.22 | 0 |
| TXA | 5356 ± 790 | 25.41 ± 2.6 | 1.25 ± 0.28 | 182.9 ± 33.21 | ||
| 0.4 mg kg−1 rFVIII | 4581 ± 662 | 22.41 ± 1.8 | 2.33 ± 0.74 | 0 | ||
| 0.4 mg kg−1 rFVIII and TXA | 4011 ± 873 | 20.95 ± 3.2 | 1 ± 0.33 | 157.8 ± 29.86 | ||
| 0.7 mg kg−1 rFVIII | 1907 ± 558 | 8.72 ± 1.1 | 2.58 ± 0.7 | 0 | ||
| 0.7 mg kg−1 rFVIIa and TXA | 2761 ± 972 | 10.99 ± 3.3 | 0.5 ± 0.29 | 130.4 ± 15.32 | ||
| WT | 506 ± 107 | 4.87 ± 0.6 | 0 ± 0 | 0 | ||
| 5A-D | t-PA WT mice | Vehicle | 8793 ± 981 | 26.2 ± 2 | 2.13 ± 0.4 | - |
| t-PA−/− mice | 7744 ± 484 | 32.3 ± 1.3 | 0.88 ± 0.023 | - | ||
| t-PA WT mice | 0.7 mg kg−1 rFVIIa | 3975 ± 934 | 17.7 ± 3.2 | 2.5 ± 0.85 | - | |
| t-PA−/− mice | 4509 ± 910 | 20.7 ± 3 | 3 ± 1.36 | - | ||
| t-PA WT mice | 1.5 mg kg−1 rFVIIa | 2627 ± 877 | 13 ± 3.7 | 2 ± 0.78 | - | |
| t-PA−/− mice | 2280 ± 788 | 9.2 ± 1.9 | 4 ± 1.19 | - | ||
| t-PA WT mice | 2.7 mg kg−1 rFVIIa | 710 ± 216 | 6.1 ± 1 | 2 ± 1.09 | - | |
| t-PA−/− mice | 765 ± 208 | 5.8 ± 1.1 | 1 ± 0.86 | - | ||
| t-PA WT mice | No induced HA | 759 ± 123 | 5 ± 0.3 | 0.13 ± 0.13 | - | |
| t-PA−/− mice | 1191 ± 591 | 4.7 ± 0.3 | 0 ± 0 | - | ||
| 5E-H | Plg WT mice | Vehicle | 5477 ± 468 | 25.4 ± 2.4 | 1.38 ± 0.26 | - |
| Plg−/− mice | 5437 ± 606 | 27.2 ± 1.5 | 1.81 ± 0.35 | - | ||
| Plg WT mice | 0.7 mg kg−1 rFVIIa | 4797 ± 1034 | 17.6 ± 2.8 | 3.1 ± 0.72 | - | |
| Plg−/− mice | 4975 ± 1138 | 16 ± 3.8 | 1.57 ± 0.65 | - | ||
| Plg WT mice | 1.5 mg kg−1 rFVIIa | 3087 ± 1305 | 13.1 ± 3.6 | 3.14 ± 1.03 | - | |
| Plg−/− mice | 2262 ± 957 | 10.2 ± 2.7 | 1.13 ± 0.55 | - | ||
| Plg WT mice | 2.7 mg kg−1 rFVIIa | 1735 ± 325 | 9.4 ± 1.8 | 3.13 ± 1.04 | - | |
| Plg−/− mice | 2288 ± 803 | 10.1 ± 2.8 | 2.67 ± 1.07 | - | ||
| Plg WT mice | No induced HA | 760 ± 189 | 5.0 ± 0.4 | 0.14 ± 0.14 | - | |
| Plg−/− mice | 983 ± 344 | 5.3 ± 0.4 | 0 ± 0 | - |
FVIII, coagulation factor VIII; Hgb, hemoglobin; Plg, plasminogen; rFVIIa, activated recombinant factor VII; rFVIII, recombinant factor VIII; t-PA, tissue-type plasminogen activator; WT, wild type. Values are shown as mean ± standard error of the mean.