Consequences of delayed therapy for sports‐related bleeds in patients with mild‐to‐moderate haemophilia and type 3 von Willebrand's disease not on prophylaxis

two of the reported mutations involve cysteine residues and as cysteines are critical for VWF folding and multimerization, this change would have profound biological and hence clinical significance in this type of disease. We have also demonstrated the highly conserved nature of Cys410 across a number of species. Our patient has major bleeding symptoms, and aside from the suggested defective synthesis of large multimers, it is highly likely that as seen from the recombinant expression studies together with the DDAVP data, there may be an almost total absence of functional VWF. In a recent novel study by Zhou et al., [9], using electron microscopy (EM) of the VWF at molecule level, the authors report a detailed account of disulphide linkages and the structure of homologous domains of VWF with further sequence analysis and tests of domain boundaries by truncation. In combination with EM findings, these studies provide a comprehensive view of the architecture of individual domains and how they are organized within the VWF. These findings have furthered the role of D1 and D2 domains and have clarified their role on how mature VWF is stored and finally released from the Weibel-Palade bodies. Identification of mutations causing type 2A(IIC) VWD, together with such comprehensive studies of VWF molecule domains would help in better understanding of VWF and VWD. In summary, we have identified a homozygous p.Cys410Ser mutation in a family with type 2A(IIC) VWD. Expression of this mutation simulated the defective secretion of abnormal VWF as seen in the homozygous patients, but not the heterozygous parents or the brother, indicating the recessive nature of this mutation causing this sub-type compared with the other dominant type 2 VWD. Although the phenotypic testing of these families would aid the diagnosis of these very rare sub-types genetic testing would confirm and identify the pathogenic mechanism of these haemostatic abnormalities. An assured diagnosis would also help in providing a better genetic counselling in countries, such as Iran, where these diseases are more common due to widespread practice of consanguineous marriage.