PhD defence F. (Ferdows) Atiq

Dissertation in short:

Von Willebrand disease (VWD) is the most common inherited bleeding disorder. VWD is caused by reduced von Willebrand factor (VWF) levels or an abnormal function of VWF. Patients with VWD have mucocutaneous bleeding, such as epistaxis, menorrhagia and postsurgical bleeding. Patients with VWD have a reduced quality of life compared to the general population. We have performed a nationwide study in 834 patient with VWD in the Netherlands. Our aims were to obtain novel insights in clinically relevant aspects of VWD, such as the genetic background, diagnosis, quality of life, understanding the heterogeneity in VWF levels and bleeding phenotype of VWD patients, and treatment of VWD. Some of the main findings in this thesis were (1) the identification of important differences in the pathophysiology, VWF and FVIII levels, bleeding phenotype and desmopressin response between type 1 VWD patients with and without a VWF gene variant. (2) Validation of the accuracy of VWF multimer densitometric analysis in VWD diagnosis in clinical practice. (3) The incidence of bleeding suggest that 0.60 IU/mL, which is the lower limit of normal, should be used as cut-off value to diagnose low VWF, instead of 0.50 IU/mL which is currently used. (4) The diagnostic delay was markedly prolonged in women with bleeding disorders compared to men, suggesting that more awareness should be raised about women with bleeding disorders. (5) Lastly we found that comorbidities, body-mass index, and hemostatic response during hemostatic challenges are important determinants of VWF levels and bleeding phenotype of VWD patients.