Von Willebrand Disease - History

History

In 1924, a 5-year-old girl who lived on the Åland Islands was brought to Deaconess Hospital in Helsinki, Finland, where she was seen by Dr. Erik von Willebrand. He ultimately assessed 66 members of her family and reported in 1926 that this was a previously undescribed bleeding disorder that differed from hemophilia. Dr von Willebrand recognized the autosomal inheritance pattern, and noted that the bleeding symptoms were greater in children and in women of childbearing age. Thus, he stated that patients with this syndrome had (1) mucocutaneous bleeding, (2) normal clotting time, (3) autosomal inheritance rather than being linked to the X chromosome, and (4) prolonged bleeding times by the Duke method (ear lobe bleeding time). He subsequently found that blood transfusions were useful not only to correct the anemia but also to control bleeding.

In the 1950s, it became clear that a "plasma factor," antihemophilic factor (FVIII), was decreased in these persons and that Cohn fraction I-0 could correct both the plasma deficiency of FVIII and the prolonged bleeding time. Since this time, the factor causing the long bleeding time was called "von Willebrand factor" in honor of Dr. Erick von Willebrand.

Variant forms of VWF were recognized in the 1970s, and we now recognize that these variations are the result of synthesis of an abnormal protein.

During the 1980s, molecular and cellular studies distinguished hemophilia A and vWD more precisely. Persons who had vWD had a normal FVIII gene on the X chromosome, and some had an abnormal vWF gene on chromosome 12. Gene sequencing identified many of these persons as having a vWF gene mutation. The genetic causes of milder forms of low vWF are still under investigation, and these forms may not always be caused by an abnormal vWF gene.