Commentary to Erik von Willebrand’s original paper from 1926 ‘Hereditär pseudohemofili’
1999; Wiley; Volume: 5; Issue: 3 Linguagem: Inglês
10.1046/j.1365-2516.1999.0320a.x
ISSN1365-2516
Autores Tópico(s)Hemophilia Treatment and Research
ResumoHaemophiliaVolume 5, Issue 3 p. 220-221 Free Access Commentary to Erik von Willebrand's original paper from 1926 'Hereditär pseudohemofili' Nilsson, Nilsson Department for Coagulation Disorders, University Hospital, Malmö, SwedenSearch for more papers by this author Nilsson, Nilsson Department for Coagulation Disorders, University Hospital, Malmö, SwedenSearch for more papers by this author First published: 25 December 2001 https://doi.org/10.1046/j.1365-2516.1999.0320a.xCitations: 3 Inga MarieNilsson Department for Coagulation Disorders, University Hospital, S-205 02 Malmö, Sweden. AboutSections ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat In 1926, Doctor Erik von Willebrand from the Department of Medicine at the Diakonihospital in Helsinki published his first paper on a bleeding disease that he had observed in several members of a family from Föglö, on the islands of Åland in the Gulf of Bothnia between Sweden and Finland. The title of his paper was 'Hereditär pseudohemofili' and it was published in Finska Läkaresällskapets Handlingar, Band LXVII N:2, 1926. The paper was written in Swedish, but with a German summary. Thus only people speaking Swedish have been able to read the original paper. In spite of this the article has become a classic, where the history of von Willebrand disease is concerned. This is most probably due to the fact that in the following papers, which were written in German, von Willebrand gave a detailed review of his first paper. Furthermore, the paper attracted attention among Scandinavian research workers interested in bleeding disorders and they referred to it in English in their articles. Now Professor Emeritus Peter Wahlberg, who was head of the Department of Internal Medicine at Centralsjukhuset in Mariehamn, Åland, has translated the original paper into English, so it is available to all researchers in the field of von Willebrand disease. The first paper by Doctor Erik von Willebrand, who later was appointed Professor, is really impressive, inspiring respect for clinical observations made more than 70 years ago. It is clear that von Willebrand had followed the literature of the day carefully, and he knew the few methods available at that time for investigation of a patient with a haemorrhagic diathesis. I regard von Willebrand as an eminent scientist and he had some of the properties that I saw in my boss – the late Professor Jan Waldenström. He was intelligent and observant, with a good knowledge of what was happening at the research front, he had intuition, imagination and the talent to form associations. I also feel that he was quite consageous, which is necessary for a researcher putting forward something new. His first case was a girl, S. Hjördis, who was 5 years old when in April 1924 she was admitted to the Department of Medicine (where von Willebrand served at the Diakonihospital in Helsinki), because of a severe haemorrhagic disorder. Hjördis came from Föglö, a small island in the archipelago of Åland. She was one of 12 siblings, all but two of whom had had bleeding symptoms. Four of her sisters had died between the ages of 2 and 4 years of uncontrollable bleeding from the nose, from wounds and from the intestinal canal. Both parents, Oskar and Augusta, had been troubled by severe nose bleedings in their youth, and Augusta as well as several of her sisters had had profuse menstrual bleedings. Hjördis herself had had several severe bleeding episodes from the nose and lips and following tooth extractions. Her bleeding episodes are described in detail in the von Willebrand paper. From later reports we know that Hjördis bled to death at the age of 14 years, during her fourth menstrual period. In his original paper von Willebrand presented a pedigree of the family from Åland. He studied 66 members of the family and found 23 bleeders. This family has since been studied extensively, especially by Lehmann (1959) and Eriksson (1961), and remains the family with by far the largest number of members known to have von Willebrand disease. In his original paper, von Willebrand gave a detailed description of the disease. The predominant symptoms were nose bleeding, bleeding from the gums and after tooth extraction, bleeding from the female genital tract and bleeding from trivial wounds. He stressed that joint bleedings, common in haemophilia, were relatively rare. He found the bleeding time to be prolonged despite a normal platelet count. The platelets were morphologically normal. Coagulation time and clot extraction were normal. He considered blood transfusions useful, not only to replace blood loss, but also to control bleeding. Concerning the heredity of the disease, von Willebrand consulted a specialist in genetics, Professor Federley in Helsinki. The disease was believed to be inherited as an autosomal dominant trait and above all manifested in women. However, the hereditary studies are not conclusive in his first paper. Von Willebrand maintained that the disease was clearly distinguishable from that described by Glanzmann as thrombasthenia in 1918. He concluded that the disorder, which affects both sexes, was a previously unknown form of haemophilia, and he called it hereditary pseudohaemophilia. He stressed that a prolonged bleeding time was its most important characteristic. Von Willebrand felt that the bleeding could be best explained as the combined effect of a functional disorder of the platelets and a systemic lesion of the vessel wall. This first description of the now well-known von Willebrand disease is without question epoch-making and his findings are still relevant. In 1933 von Willebrand began to collaborate with a German physician, Rudolf Jürgens. This co-operation led to the disease being called von Willebrand–Jürgens thrombopathy. Fortunately this name is no longer used. Erik von Willebrand died in 1949 at the age of 79 years. His special interests outside medicine were ornithology, nature conservation and racial problems. Remarkably enough Erik von Willebrand never visited the island of Föglö. In memory of Erik von Willebrand the Åland community issued a stamp in 1994 bearing his name. In this connection it seems appropriate to mention the discovery of the plasma factor that is responsible for the bleeding defect in von Willebrand disease and which has been given the name von Willebrand factor. In the 1950s, several authors described patients with a combined defect, a prolonged bleeding time and decreased factor VIII activity. The prolonged bleeding time was believed to be due to a defect in the vessel wall, and the syndrome was called vascular haemophilia. In Sweden in 1956 and 1957 several families with a severe bleeding disorder characterized by factor VIII deficiency and a prolonged bleeding time were also described. At that time the novel human fraction I-0 obtained by treating Cohn's fraction I with 1 M glycine solution had just become available [ 1]. This fraction was given to the patients with the combined bleeding defect and was found to correct the factor VIII deficiency as well as the prolonged bleeding time and capillary bleeding [ 234]. This finding indicated that the prolonged bleeding time was due to deficiency of a plasma factor present in normal plasma. The clinical symptoms in the Swedish cases closely resembled those described by von Willebrand. In June 1957, Margareta Blombäck, Erik Jorpes, Inga Marie Nilsson and a young student, Stig-Arne Johansson, made an expedition – quite dramatic and with a whole laboratory of equipment – to Åland and studied 15 patients, some of whom belonged to von Willebrand's original series. We found a decreased factor VIII activity, and fraction I-0 given to one of the patients corrected the prolonged bleeding time. These investigations thus showed that the bleeding disorder characterized by a reduced factor VIII level and prolonged bleeding time was identical to that described by von Willebrand in 1926. It also had become clear that the impaired haemostasis in von Willebrand disease was due to the lack of a hitherto unknown plasma factor, which was called von Willebrand factor. In September 1958 Centeon arranged a conference on Åland concerning von Willebrand disease. An excursion to Föglö was arranged and after 40 years, Margareta Blombäck and I met four of the patients we had studied on our expedition to Åland in 1957, two sisters and one brother to Hjördis and the brother's son. This was a very nostalgic experience. This meeting on Åland was a dignified tribute to Erik von Willebrand and especially to his first original paper. References 1 Blombäck B & Blombäck M. Purification of human and bovine fibrinogen. Arkiv Kemi 1956; 19: 415 43. Google Scholar 2 Nilsson IM, Blombäck B, Blombäck M, Svennerud S. Kvinnlig hämofili och deras behandling med humant antihemofiliglobulin. Nord Med 1956; 56: 1654 63. PubMedGoogle Scholar 3 Nilsson IM, Blombäck M, Von Franken I. On an inherited autosomal hemorrhagic diathesis with antihemofiliglobulin (AHG) deficiency and prolonged bleeding time. Acta Med Scand 1957; 159: 35 57. Wiley Online LibraryCASPubMedWeb of Science®Google Scholar 4 Nilsson IM, Blombäck M, Jorpes E, Blombäck B, Johansson SA. V. Willebrand's disease and its correction with human plasma fraction I-0. Acta Med Scand 1957; 159: 179 88. Wiley Online LibraryCASPubMedWeb of Science®Google Scholar Citing Literature Volume5, Issue3May 1999Pages 220-221 ReferencesRelatedInformation
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