A modified FVIII protein comprising a cysteine substitution mutation at an amino acid position in the amino acid sequence of SEQ ID NO: 1 selected from the group of amino acid positions consisting of: i. 2094, 2186, 2204, 2206, 59, 490, 493, 555, 568, 582, 1778, 1793, 1794, 1797, 1798, 1799, 1800, 1801, 1806, 1811, 1814, 1816, 1818, 1891, 2035, 2068, 2092, 2093, 2095, 2125, 2183, 2191, 2196, and 2212; or ii. 2094, 2186, 2204, 2206, 59, 239, 333, 336, 379, 481, 484, 486, 488, 489, 490, 492, 493, 495, 496, 497, 499, 500, 501, 507, 555, 562, 568, 571, 582, 1680, 1778, 1793, 1794, 1797, 1798, 1799, 1800, 1801, 1806, 1810, 181 1, 1814, 1816, 1818, 1891, 2035, 2068, 2092, 2093, 2095, 21 18, 2125, 2183, 2191, 2196, and 2212; wherein when the amino acid position is selected from group ii: (a) the modified FVIII protein further comprises at least one additional substitution other than cysteine at position 336, 562, 1680 or 1968 in the amino acid sequence of SEQ ID NO:1 selected from the group consisting of: R336A, R562A, Y1680F and K1968A, (b) the modified FVIII protein further comprises two additional substitutions other than cysteine at positions 336 and 1680 in the amino acid sequence of SEQ ID NO: 1, wherein said substitutions are R336A and Y1680F, or (c) the modified FVIII protein comprises amino acid substitutions at positions 336, 1680, 2094, 2186, 2204, or 2206 with reference to the amino acid sequence of SEQ ID NO: 1, where the substitutions are selected from the group consisting of: a) S2094C, R336A and Y1680F; b) S2186C, R336A and Y1680F; c) S2204C, R336A and Y1680F; d) S2206C, R336A and Y1680F; e) S2094C and R336A; f) S2186C and R336A; g) S2204C and R336A; h) S2206C and R336A; i) S2094C and Y1680F; j) S2186C and Y1680F; k) S2204C and Y1680F; I) S2206C and Y1680F; m) S2094C; n) S2186C; o) S2204C; and p) S2206C. i. 2094, 2186, 2204, 2206, 59, 490, 493, 555, 568, 582, 1778, 1793, 1794, 1797, 1798, 1799, 1800, 1801, 1806, 1811, 1814, 1816, 1818, 1891, 2035, 2068, 2092, 2093, 2095, 2125, 2183, 2191, 2196, and 2212; or ii. 2094, 2186, 2204, 2206, 59, 239, 333, 336, 379, 481, 484, 486, 488, 489, 490, 492, 493, 495, 496, 497, 499, 500, 501, 507, 555, 562, 568, 571, 582, 1680, 1778, 1793, 1794, 1797, 1798, 1799, 1800, 1801, 1806, 1810, 181 1, 1814, 1816, 1818, 1891, 2035, 2068, 2092, 2093, 2095, 21 18, 2125, 2183, 2191, 2196, and 2212; wherein when the amino acid position is selected from group ii: (a) the modified FVIII protein further comprises at least one additional substitution other than cysteine at position 336, 562, 1680 or 1968 in the amino acid sequence of SEQ ID NO:1 selected from the group consisting of: R336A, R562A, Y1680F and K1968A, (b) the modified FVIII protein further comprises two additional substitutions other than cysteine at positions 336 and 1680 in the amino acid sequence of SEQ ID NO: 1, wherein said substitutions are R336A and Y1680F, or (c) the modified FVIII protein comprises amino acid substitutions at positions 336, 1680, 2094, 2186, 2204, or 2206 with reference to the amino acid sequence of SEQ ID NO: 1, where the substitutions are selected from the group consisting of: a) S2094C, R336A and Y1680F; b) S2186C, R336A and Y1680F; c) S2204C, R336A and Y1680F; d) S2206C, R336A and Y1680F; e) S2094C and R336A; f) S2186C and R336A; g) S2204C and R336A; h) S2206C and R336A; i) S2094C and Y1680F; j) S2186C and Y1680F; k) S2204C and Y1680F; I) S2206C and Y1680F; m) S2094C; n) S2186C; o) S2204C; and p) S2206C. (a) the modified FVIII protein further comprises at least one additional substitution other than cysteine at position 336, 562, 1680 or 1968 in the amino acid sequence of SEQ ID NO:1 selected from the group consisting of: R336A, R562A, Y1680F and K1968A, (b) the modified FVIII protein further comprises two additional substitutions other than cysteine at positions 336 and 1680 in the amino acid sequence of SEQ ID NO: 1, wherein said substitutions are R336A and Y1680F, or (c) the modified FVIII protein comprises amino acid substitutions at positions 336, 1680, 2094, 2186, 2204, or 2206 with reference to the amino acid sequence of SEQ ID NO: 1, where the substitutions are selected from the group consisting of: a) S2094C, R336A and Y1680F; b) S2186C, R336A and Y1680F; c) S2204C, R336A and Y1680F; d) S2206C, R336A and Y1680F; e) S2094C and R336A; f) S2186C and R336A; g) S2204C and R336A; h) S2206C and R336A; i) S2094C and Y1680F; j) S2186C and Y1680F; k) S2204C and Y1680F; I) S2206C and Y1680F; m) S2094C; n) S2186C; o) S2204C; and p) S2206C.