Distribution of VWD type 2A mutations. A schematic representation of the A1 through A3 domain of von Willebrand factor (VWF) is shown. The A1 and A3 domains are characterized by a loop structure of 187 amino acids formed by disulfide bonds between C1272 and C1458 (A1 domain) and C1686 and C1872 (A3 domain), respectively. With the exception of C1272S all VWD type 2A mutations are located within the A2 domain of VWF. The arrow marks the proteolytic cleavage site for ADAMTS13 between residues Y1605 and M1606. The cysteines involved in loop-structure formation are shown in circles.