TABLE 4.
Thrombin generation parameter values for P4-P3′ factor VIII variants
As described under “Experimental Procedures,” thrombin generation assays were run using 1 nm factor VIII, 0.15 pm recombinant tissue factor, and 4 μm phospholipid. Values represent mean ± S.D. from at least three separate determinations.
| Factor VIII (1 nm) | Latent time | Peak time | Peak value | Endogenous thrombin potential |
|---|---|---|---|---|
| min | nm | nm min | ||
| WT | 15.7 ± 1.60 (1.0)a | 28.9 ± 2.20 (1.0) | 73.3 ± 3.3 (1.0) | 1723 ± 45 (1.0) |
| 336(P4-P2)372 | 14.7 ± 1.90 (0.9) | 27.5 ± 1.80 (1.0) | 69.0 ± 5.8 (0.9) | 1493 ± 124 (0.9) |
| 336(P1′-P3′)372 | 14.4 ± 0.79 (0.9) | 25.0 ± 0.75 (0.9) | 28.9 ± 1.5 (0.4) | 492 ± 57 (0.3) |
| 336(P4-P3′)372 | 21.1 ± 0.89 (1.3) | 31.0 ± 1.60 (1.1) | 12.0 ± 2.0 (0.2) | 230 ± 33 (0.1) |
| 336(P4-P2)740 | 14.7 ± 1.10 (0.9) | 27.9 ± 1.80 (1.0) | 34.9 ± 3.6 (0.3) | 1021 ± 152 (0.5) |
| 336(P1′-P3′)740 | 14.6 ± 1.60 (0.9) | 27.9 ± 1.60 (1.0) | 24.3 ± 1.3 (0.3) | 665 ± 87 (0.4) |
| 336(P4-P3′)740 | 18.8 ± 0.72 (1.4) | 26.0 ± 1.10 (0.9) | 6.6 ± 1.2 (0.1) | 110 ± 13 (0.1) |
| 336(P4-P3′)562 | 14.9 ± 1.40 (0.9) | 28.9 ± 1.40 (1.0) | 93.0 ± 4.3 (1.3) | 2194 ± 102 (1.3) |
| R336Q | 14.8 ± 1.20 (0.8) | 23.1 ± 0.78 (0.8) | 187.0 ± 4.1 (2.6) | 2829 ± 478 (1.6) |
a Thrombin generation parameter values relative to wild type are shown in parentheses.