The invention describes factor VIII molecules with reduced capacity to elicit activation of NKT cells, for use in the treatment of congenital and/or acquired haemophilia A and in bleeding disorders. Said factor VIII molecules having a domain structure Al-al-A2-a2-B-a3-A3-Cl-C2, in which A1, A2, B, A3, C1 and C2 represent domains and al, a2 and a3 acidic regions linking said domains, The factor VIII molecule is obtainable by: a. identification of at least one NKT cell epitope wherein said epitope comprises hydrophobic aminoacid residues in position P1 and/or P7 b. modification of said epitope(s) by eliminating at least one hydrophobic aminoacid residue in position P1 and/or P7, substituting at least one hydrophobic aminoacid residue in position P1 and/or P7 with a non-hydrophobic residue, or adding a non-hydrophobic residue in position P1 and/or P7.
