Desmopressin response and FVIII and VWF measurements before and at peak level by VWF domain
| Domain location and type of mutation . | No. of responsive patients/total . | FVIII:C, IU/dL, mean±SD . | VWF:RCo, IU/dL, mean±SD . | VWF:RCo/Ag, mean±SD . | |||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| Before . | Peak . | Fold increase . | Before . | Peak . | Fold increase . | Before . | Abn/N* . | Peak . | Abn/N . | ||
| D1-D2 | 3/3 | 59 ± 29 | 144 ± 67 | 2.5 ± 0.4 | 52 ± 31 | 120 ± 70 | 2.4 ± 0.32 | 0.87 ± 0.33 | 1/2 | 0.89 ± 0.26 | 0/3 |
| G160W | 1/1 | 56 | 119 | 2.1 | 25 | 68 | 2.3 | 0.54 | 1/0 | 0.68 | 0/1 |
| N166I | 1/1 | 90 | 220 | 2.4 | 44 | 92 | 2.1 | 1.19 | 0/1 | 0.8 | 0/1 |
| A641V | 1/1 | 32 | 98 | 2.9 | 86 | 200 | 2.3 | 0.88 | 0/1 | 1.18 | 0/1 |
| D′-D3 | 14/16 | 20 ± 21§ | 138 ± 75 | 9.7 ± 5.9∥ | 10 ± 16∥ | 87 ± 36 | 18.1 ± 11.7∥ | 0.46 ± 0.23 | 12/4 | 0.92 ± 0.25 | 1/15 |
| M771I | 1/1 | 31 | 112 | 3.6 | 22 | 101 | 4.6 | 0.65 | 0/1 | 0.96 | 0/1 |
| I1094T | 1/1 | 93 | 324 | 3.5 | 65 | 144 | 2.2 | 0.91 | 0/1 | 0.83 | 0/1 |
| C1130F/G/R (range) | 5/7 | 17 ± 9 (1.5-26) | 118 ± 62 (13-183) | 7.1 ± 2 (5.1-10.5) | 5 ± 4 (3-14) | 73 ± 29 (44-123) | 17.1 ± 5.1 (7.4-23) | 0.31 ± 0.16 (0.13-0.64) | 6/1 | 0.87 ± 0.33 (0.56-1.54) | 1/6 |
| W1144G | 1/1 | 22 | 137 | 6.2 | 16 | 101 | 6.3 | 0.48 | 1/0 | 0.91 | 0/1 |
| R1205H† (range) | 6/6 | 10 ± 3 (7-16) | 136 ± 32 (109-195) | 15.3 ± 5.9 (6.9-21.7) | 4 ± 2 (3-7) | 89 ± 42 (53-161) | 26 ± 14 (16.9-53.7) | 0.53 ± 0.19 (0.33-0.87) | 5/1 | 1 ± 0.22 (0.7-1.3) | 0/6 |
| A1-A3 | 6/14 | 46 ± 28 | 125 ± 58 | 3.1 ± 1 | 27 ± 29 | 75 ± 62 | 4 ± 2.1 | 0.54 ± 0.37 | 8/6 | 0.81 ± 0.48 | 5/9 |
| D1277 L1278delinsE | 0/1 | 36 | 109 | 3 | 3 | 15 | 5 | 0.17 | 1/0 | 0.36 | 1/0 |
| R1315C (range) | 1/3 | 24 ± 6 (17-28) | 82 ± 19 (67-103) | 3.5 ± 0.7 (2.7-4) | 11 ± 8 (3-18) | 42 ± 34 (12-79) | 4 ± 2.6 (2-7.2) | 0.58 ± 0.41 (0.19-1) | 2/1 | 1 ± 0.65 (0.31-1.58) | 1/2 |
| R1374H | 0/1 | 73 | 213 | 2.9 | 18 | 34 | 1.9 | 0.22 | 1/0 | 0.18 | 1/0 |
| R1379C | 1/1 | 107 | 266 | 2.5 | 53 | 176 | 3.3 | 0.9 | 0/1 | 1.4 | 0/1 |
| P1413L | 1/1 | 54 | 111 | 2.1 | 31 | 87 | 2.8 | 0.67 | 0/1 | 0.93 | 0/1 |
| G1415D | 0/1 | 23 | 106 | 4.6 | 3 | 18 | 6 | 0.13 | 1/0 | 0.31 | 1/0 |
| N1421K | 0/1 | 30 | 142 | 4.7 | 3 | 31 | 10.3 | 0.11 | 1/0 | 0.48 | 1/0 |
| F1520L | 1/1 | 68 | 183 | 2.7 | 91 | 200 | 2.2 | 0.98 | 0/1 | 1.2 | 0/1 |
| R1583W | 1/1 | 31 | 97 | 3.1 | 48 | 130 | 2.7 | 0.92 | 0/1 | 0.91 | 0/1 |
| Y1584C | 1/1 | 91 | 113 | 1.2 | 75 | 136 | 1.8 | 0.94 | 0/1 | 1.36 | 0/1 |
| K1794E | 0/1 | 25 | 83 | 3.3 | 6 | 38 | 3.3 | 0.29 | 1/0 | 0.73 | 0/1 |
| V1822G | 0/1 | 37 | 79 | 2.1 | 16 | 48 | 3 | 0.55 | 1/0 | 0.8 | 0/1 |
| C2304Y | 1/1 | 150 | 300 | 2 | 54 | 86 | 1.6 | 0.79 | 0/1 | 0.85 | 0/1 |
| R2313H | 1/1 | 92 | 249 | 2.7 | 73 | 136 | 1.9 | 0.86 | 0/1 | 0.85 | 0/1 |
| R2464C | 1/1 | 44 | 167 | 3.8 | 34 | 120 | 3.5 | 1 | 0/1 | 0.94 | 0/1 |
| C2477Y/S | 2/2 | 43-58 | 61-300 | 1.4-5.2 | 33-35 | 87-89 | 2.5-2.7 | 0.86-1.25 | 0/2 | 0.88-1.24 | 0/2 |
| Q2520P | 1/1 | 45 | 236 | 5.2 | 18 | 122 | 6.8 | 0.78 | 0/1 | 1.04 | 0/1 |
| Q2544X | 1/1 | 75 | 214 | 2.9 | 35 | 124 | 3.5 | 1.35 | 0/1 | 1.35 | 0/1 |
| C2693Y | 1/1 | 41 | 119 | 2.9 | 29 | 88 | 3 | 0.57 | 1/0 | 0.87 | 0/1 |
| Domain location and type of mutation . | No. of responsive patients/total . | FVIII:C, IU/dL, mean±SD . | VWF:RCo, IU/dL, mean±SD . | VWF:RCo/Ag, mean±SD . | |||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| Before . | Peak . | Fold increase . | Before . | Peak . | Fold increase . | Before . | Abn/N* . | Peak . | Abn/N . | ||
| D1-D2 | 3/3 | 59 ± 29 | 144 ± 67 | 2.5 ± 0.4 | 52 ± 31 | 120 ± 70 | 2.4 ± 0.32 | 0.87 ± 0.33 | 1/2 | 0.89 ± 0.26 | 0/3 |
| G160W | 1/1 | 56 | 119 | 2.1 | 25 | 68 | 2.3 | 0.54 | 1/0 | 0.68 | 0/1 |
| N166I | 1/1 | 90 | 220 | 2.4 | 44 | 92 | 2.1 | 1.19 | 0/1 | 0.8 | 0/1 |
| A641V | 1/1 | 32 | 98 | 2.9 | 86 | 200 | 2.3 | 0.88 | 0/1 | 1.18 | 0/1 |
| D′-D3 | 14/16 | 20 ± 21§ | 138 ± 75 | 9.7 ± 5.9∥ | 10 ± 16∥ | 87 ± 36 | 18.1 ± 11.7∥ | 0.46 ± 0.23 | 12/4 | 0.92 ± 0.25 | 1/15 |
| M771I | 1/1 | 31 | 112 | 3.6 | 22 | 101 | 4.6 | 0.65 | 0/1 | 0.96 | 0/1 |
| I1094T | 1/1 | 93 | 324 | 3.5 | 65 | 144 | 2.2 | 0.91 | 0/1 | 0.83 | 0/1 |
| C1130F/G/R (range) | 5/7 | 17 ± 9 (1.5-26) | 118 ± 62 (13-183) | 7.1 ± 2 (5.1-10.5) | 5 ± 4 (3-14) | 73 ± 29 (44-123) | 17.1 ± 5.1 (7.4-23) | 0.31 ± 0.16 (0.13-0.64) | 6/1 | 0.87 ± 0.33 (0.56-1.54) | 1/6 |
| W1144G | 1/1 | 22 | 137 | 6.2 | 16 | 101 | 6.3 | 0.48 | 1/0 | 0.91 | 0/1 |
| R1205H† (range) | 6/6 | 10 ± 3 (7-16) | 136 ± 32 (109-195) | 15.3 ± 5.9 (6.9-21.7) | 4 ± 2 (3-7) | 89 ± 42 (53-161) | 26 ± 14 (16.9-53.7) | 0.53 ± 0.19 (0.33-0.87) | 5/1 | 1 ± 0.22 (0.7-1.3) | 0/6 |
| A1-A3 | 6/14 | 46 ± 28 | 125 ± 58 | 3.1 ± 1 | 27 ± 29 | 75 ± 62 | 4 ± 2.1 | 0.54 ± 0.37 | 8/6 | 0.81 ± 0.48 | 5/9 |
| D1277 L1278delinsE | 0/1 | 36 | 109 | 3 | 3 | 15 | 5 | 0.17 | 1/0 | 0.36 | 1/0 |
| R1315C (range) | 1/3 | 24 ± 6 (17-28) | 82 ± 19 (67-103) | 3.5 ± 0.7 (2.7-4) | 11 ± 8 (3-18) | 42 ± 34 (12-79) | 4 ± 2.6 (2-7.2) | 0.58 ± 0.41 (0.19-1) | 2/1 | 1 ± 0.65 (0.31-1.58) | 1/2 |
| R1374H | 0/1 | 73 | 213 | 2.9 | 18 | 34 | 1.9 | 0.22 | 1/0 | 0.18 | 1/0 |
| R1379C | 1/1 | 107 | 266 | 2.5 | 53 | 176 | 3.3 | 0.9 | 0/1 | 1.4 | 0/1 |
| P1413L | 1/1 | 54 | 111 | 2.1 | 31 | 87 | 2.8 | 0.67 | 0/1 | 0.93 | 0/1 |
| G1415D | 0/1 | 23 | 106 | 4.6 | 3 | 18 | 6 | 0.13 | 1/0 | 0.31 | 1/0 |
| N1421K | 0/1 | 30 | 142 | 4.7 | 3 | 31 | 10.3 | 0.11 | 1/0 | 0.48 | 1/0 |
| F1520L | 1/1 | 68 | 183 | 2.7 | 91 | 200 | 2.2 | 0.98 | 0/1 | 1.2 | 0/1 |
| R1583W | 1/1 | 31 | 97 | 3.1 | 48 | 130 | 2.7 | 0.92 | 0/1 | 0.91 | 0/1 |
| Y1584C | 1/1 | 91 | 113 | 1.2 | 75 | 136 | 1.8 | 0.94 | 0/1 | 1.36 | 0/1 |
| K1794E | 0/1 | 25 | 83 | 3.3 | 6 | 38 | 3.3 | 0.29 | 1/0 | 0.73 | 0/1 |
| V1822G | 0/1 | 37 | 79 | 2.1 | 16 | 48 | 3 | 0.55 | 1/0 | 0.8 | 0/1 |
| C2304Y | 1/1 | 150 | 300 | 2 | 54 | 86 | 1.6 | 0.79 | 0/1 | 0.85 | 0/1 |
| R2313H | 1/1 | 92 | 249 | 2.7 | 73 | 136 | 1.9 | 0.86 | 0/1 | 0.85 | 0/1 |
| R2464C | 1/1 | 44 | 167 | 3.8 | 34 | 120 | 3.5 | 1 | 0/1 | 0.94 | 0/1 |
| C2477Y/S | 2/2 | 43-58 | 61-300 | 1.4-5.2 | 33-35 | 87-89 | 2.5-2.7 | 0.86-1.25 | 0/2 | 0.88-1.24 | 0/2 |
| Q2520P | 1/1 | 45 | 236 | 5.2 | 18 | 122 | 6.8 | 0.78 | 0/1 | 1.04 | 0/1 |
| Q2544X | 1/1 | 75 | 214 | 2.9 | 35 | 124 | 3.5 | 1.35 | 0/1 | 1.35 | 0/1 |
| C2693Y | 1/1 | 41 | 119 | 2.9 | 29 | 88 | 3 | 0.57 | 1/0 | 0.87 | 0/1 |
Mutations in italics are associated with abnormal multimeric pattern.
Abnormal/normal ratio (>0.59).
Patients with additional M740I change were included in this group since basal and peak levels for FVIII:C and VWF:RCo were similar to those with R1205H.
Including 3 patients with basal abnormal VWF multimers
P < .05 versus no-mutations subgroup (all P values were adjusted for multicomparison tests).
P < .01 versus no-mutations subgroup (all P values were adjusted for multicomparison tests).