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Eighty years ago, Erik A. von Willebrand published his first paper (Finska Läkaresällskapets Handlingar, 1926) about a bleeding disease he had observed in several members of a family from Föglö in the Åland archipelago in the Gulf of Bothnia. His first case was a girl, Hjördis S., who was 7 years old when first examined. Hjördis was one of 12 siblings, all but two of whom had experienced bleeding symptoms. Four of the sisters had died of uncontrollable bleeding at a young age. Hjördis herself had had several severe episodes of bleeding from the nose and lips and following tooth extractions. At the age of 13, she bled to death during her fourth menstrual period. Erik von Willebrand subsequently studied 66 family members and found that 23 of them had symptoms of the same type as Hjördis. He concluded that the condition was a previously unknown form of hemophilia, which affected both sexes, and he called it hereditary pseudohemophilia. Since this early observation, von Willebrand disease has been extensively studied. In 1957 Nilsson and co-workers concluded that the impaired hemostasis was due to lack of a plasma factor –the von Willebrand factor – present both in normal and in hemophilia A plasma. This knowledge made it possible to introduce the first steps towards effective replacement therapy. Today, we know the structure and function of the von Willebrand factor and much of its molecular biology. With the availability of safe and effective products, the treatment is continually improving.
Erik A. von Willebrand was born in Vasa, Finland, in 1870 and died in 1949. |
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Von Willebrand disease (VWD) is the most common inherited bleeding disorder [1] and is caused by quantitative (types 1 and 3) or qualitative (types 2A, 2B, 2M, 2N) defects of von Willebrand factor (VWF) [2]. VWD is classified into three major categories based on type of defect and degree of deficiency of von Willebrand factor (VWF). Type 1 is the most common, affecting approximately 55-70% of those who are symptomatic with VWD [3] with type 2 making up most of the remainder. Type 3, the most severe form of VWD, is rare, estimated to affect from 0.1 to 5.3 individuals per million people [4].
The leading symptom in VWD is bleeding, chiefly of the mucosal type, for example, severe nose-bleeding (epistaxis), gastrointestinal bleeding, and abnormal or heavy menstrual bleeding (menorrhagia). In the most serious forms of VWD characterized also by very reduced levels of FVIII (2-10 U/dL), joint and muscle bleeding, resembling that seen in moderate hemophilia A, may also be observed. Strategies for treatment vary by type and severity, and include DDAVP (desmopressin acetate), use of antifibrinolytics, and therapy to replace the von Willebrand factor (VWF) proteins that are missing [5].
Replacement therapy to prevent bleeding, called prophylaxis, has been used to treat patients with VWD that is unresponsive to other treatment [6]. The rationale for initiating long-term prophylaxis in VWD is that it has been successfully used in severe hemophilia, showing that it is feasible to implement early in life in a home setting, and that prevention of bleeding and its consequences is possible [7, 8]. |
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The photograph above was taken in Föglö in the Åland
archipelago. It depicts Professor Inga Marie Nilsson and
a brother of Hjördis S. They hold a pedigree based on
the one described by Erik von Willebrand in his 1926
publication. |
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