There are multiple factors that affect the plasma concentration of VWF. A major contributor is blood group. On average, levels are lower in blood group O individuals in comparison to non-blood group O individuals. Why the difference? The blood group A and B alleles encode glycosyltransferases that add carbohydrate moieties to the precursor side chains, converting them to the A or B antigens. The O alleles do not encode this transferase and thus express the unmodified precursor. VWF undergoes glycosylation, and the ABO carbohydrate structures have been identified within the A1 domain of the protein. Although the exact mechanism is unknown, one hypothesis is that the reduced level of glycosylated VWF in individuals with blood group O is associated with decreased survival of the protein.1
Factors associated with higher vWF levels include race (15% higher in African Americans), chronic inflammation, acute infection/trauma, pregnancy, oral estrogen replacement, birth control pill use, age (higher in neonates), diabetes, malignancy, stress, surgery, and exercise. A factor associated with reduced VWF level is hypothyroidism.