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Semin Thromb Hemost 2022; 48(08): 911-925
DOI: 10.1055/s-0042-1749088
Review Article

A Review of Autoimmune Acquired von Willebrand Factor Deficiency in Japan

Akitada Ichinose
1   Department of Molecular Patho-Biochemistry and Patho-Biology, Yamagata University School of Medicine, Yamagata, Japan
2   The Japanese Collaborative Research Group (JCRG) on Autoimmune Acquired Coagulation Factor Deficiencies supported by the Japanese Ministry of Health, Labor and Welfare (MHLW), Yamagata, Japan
,
Tsukasa Osaki
1   Department of Molecular Patho-Biochemistry and Patho-Biology, Yamagata University School of Medicine, Yamagata, Japan
2   The Japanese Collaborative Research Group (JCRG) on Autoimmune Acquired Coagulation Factor Deficiencies supported by the Japanese Ministry of Health, Labor and Welfare (MHLW), Yamagata, Japan
3   Department of Public Health and Hygiene, Yamagata University Graduate School of Medical Science, Iida-Nishi, Yamagata, Japan
,
Masayoshi Souri
1   Department of Molecular Patho-Biochemistry and Patho-Biology, Yamagata University School of Medicine, Yamagata, Japan
2   The Japanese Collaborative Research Group (JCRG) on Autoimmune Acquired Coagulation Factor Deficiencies supported by the Japanese Ministry of Health, Labor and Welfare (MHLW), Yamagata, Japan
3   Department of Public Health and Hygiene, Yamagata University Graduate School of Medical Science, Iida-Nishi, Yamagata, Japan
,
Emmanuel J. Favaloro 
4   Department of Haematology, Sydney Centres for Thrombosis and Haemostasis, Institute of Clinical Pathology and Medical Research (ICPMR), NSW Health Pathology, Westmead, New South Wales, Australia
5   Faculty of Science and Health, Charles Sturt University, Wagga Wagga, New South Wales, Australia
› Author Affiliations Funding This study was supported in part by research aids to A.I. from the Japanese Ministry of Health, Labor, and Welfare (21FC1008).
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Abstract

von Willebrand factor (VWF) forms high-molecular-weight multimers and plays an essential role in hemostasis, and thus its deficiency leads to bleeding symptoms. Acquired von Willebrand syndrome (AVWS) is rare, but potentially underdiagnosed, and develops in various underlying disorders. AVWS caused by anti-VWF autoantibodies is a rare subcategory of AVWS that can also be referred to as autoimmune VWF deficiency (AiVWFD). We performed a search of patients with autoimmune coagulation factor deficiencies in our nationwide survey in Japan. Among these, suspected cases of AiVWFD were extremely few, with only 11 case consultations in the last 10 years. Of these, three and five were respectively positive for anti-VWF autoantibodies (anti-VWF-Ab) and VWF inhibitor (VWF-inh). We also performed an extensive literature search of other cases from Japan, and in total, 40 cases were finally identified to have AiVWFD, with mean age of 55.0 years. Most underlying disorders were lympho- or myeloproliferative diseases, followed by autoimmune diseases. The major bleeding sites were subcutaneous and mucosal, the bleeding severity was moderate, and there were no hemorrhagic deaths. Bleeding time was prolonged; factor VIII activity, VWF antigen, and VWF activity were decreased, and high-molecular-weight VWF multimers were absent or decreased. These are similar to the common abnormal laboratory findings observed among general AVWS cases. Hemostatic therapy often involved VWF concentrates and vasopressin, and antibody eradication therapy often included corticosteroids and achieved remission. Notably, of all cases, 68% had anti-VWF-Abs, and 83% of anti-VWF-Ab-positive patients were also VWF-inh positive. To accumulate precise clinical information on AiVWFD, it is necessary to verify and improve the measurement methods for both anti-VWF-Ab and anti-VWF-inh. These findings from Japan should be confirmed in other geographic localities.

Keywords

von Willebrand factor - deficiency - inhibitor - autoantibody - neutralizing antibody - nonneutralizing antibody - lymphoproliferative disease

Authors' Contributions

A.I. initiated and designed the study, extracted data, wrote, edited, and proofread the manuscript. T.O. conducted experimental examinations, statistical analyses, and proofread the manuscript. M.S. performed experimental examinations, and proofread the manuscript. E.J.F. inspired the study, and critically edited the manuscript.


Supplementary Material



Publication History

Article published online:
08 July 2022

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