A Review of Autoimmune Acquired von Willebrand Factor Deficiency in Japan

Abstract

Abstractvon 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.

Autoimmune acquired factor XIII deficiency in Japan 2021 update: Focused on annual incidence and clinical features

“…When Roman numerals (grades I, II, and III) were converted to Arabic numerals (1, 2, and 3, respectively) the mean bleeding severity of AiF13D was 2.9, which is clearly higher than that of other AiCFDs, such as 1.9 of AiVWFD. 5 In this study, the mean FXIII activity of AiF13D cases was 4.9 ± 2.0% (n = 33; median 4%) (Table 1), which was lower compared to our previous report where the mean FXIII activity was 10.5 ± 8.5% (n = 32; median 7%). Approximately half (53%) of the AiF13D patients had <5% FXIII activity.…”

“…Immunological anti-FXIII antibody detection methods do not overlook neutralizing antibodies (i.e., FXIII inhibitors) or non-neutralizing antibodies. Therefore, detection of anti-coagulation factor antibodies is highly recommended for any type of AiCFD (AiF8D, AiF5D, 3 AiVWFD, 5 and AiF10D 4 ).…”

Autoimmune Diseases Affecting Hemostasis: A Narrative Review

“…Additional common mechanisms of AVWS include absorption of VWF on malignant cells, reduced production (e.g., as in hypothyroidism), and increased blood platelet count such as in essential thrombocythemia. Nevertheless, a proportion of AVWS cases do have an autoimmune basis (e.g., arise in autoimmune disorders such as SLE, scleroderma, and APS), or else are associated with production of autoantibodies against VWF [ 52 , 53 ].…”

“…Several hundred cases of AVWS have been reported in the medical literature to date, but numbers may be higher because of under-reporting, or misreporting as congenital VWD. The number of autoimmune AVWS cases is not known, although a recent assessment indicated these can be identified, providing clinicians and laboratories perform the appropriate investigations [ 53 ]. Treatment of AVWS depends on the underlying cause of the condition, but if an immune basis is identified, treatment could be supplemented with immunosuppression therapy.…”

Celebrating 50 Years of Seminars in Thrombosis and Hemostasis—Part I

“…The last article in this issue of STH with a specific bleeding theme describes the identification of autoimmune acquired von Willebrand factor (VWF) deficiency in Japan. 7 Ichinose and colleagues first discuss VWF, which forms high-molecular-weight multimers and plays an essential role in hemostasis, immobilizing platelets to sites of vascular injury. This leads to activation of platelets, release of granule components, platelet aggregation, and facilitation of secondary hemostasis.…”