Genetic Background of Patients With Low Von Willebrand Factor Levels

Von Willebrand disease (VWD) is caused by either quantitative or qualitative von Willebrand (VWF) defects and is the commonest inherited bleeding disorder with an estimated prevalence of about 1% in the general population. According to several guidelines, patients with a mild quantitative reduction in VWF (30-50 IU/dL) should be labeled as "low VWF". Quantitatively VWF defects account for almost 75% of all cases with VWD and among them, low VWF seems to be the most common form. Studies on patients with VWD reported only around 50% VWF mutations in low VWF cases indicating that some possible genes outside of the VWF gene may be responsible for the low VWF levels. To date, using genome-wide association study (GWAS) more than 19 non-VWF loci (such as ABO blood group system, Stabilin 2, Scavenger Receptor Class A Member 5, C-Type Lectin Domain Family 4 Member M, etc.) were identified to be associated with VWF levels. The identified genes are related to different mechanisms of the VWF life-cycle such as synthesis, secretion, glycosylation, or clearance. Despite the importance of the genetic background of low VWF levels for understanding its etiology, this issue is not well investigated yet. Thus the Low VWF Milan Cohort (LOVMIC) Study is designed to address some unanswered questions in patients with low VWF.

Inclusion Criteria for patients: * Adult patients who were diagnosed with "low VWF" and have VWF:Ag and/or VWF:RCo between 30-50 IU/dL with a ratio of VWF:RCo/VWF:Ag \> 0.6. * Subjects who have given informed consent to participate in the study according to the Declaration of Helsinki Inclusion Criteria for healthy controls: * Healthy subjects with no known bleeding disorders and with negative thrombophilia screening results * Subjects who have given informed consent to participate in the study according to the Declaration of Helsinki Exclusion Criteria: * Pregnant women * Patients with acquired von Willebrand disease syndrome