PB0260 - Immune Complex-mediated Acquired von Willebrand Syndrome in a 5-year-old Boy after Allogeneic Hematopoietic Stem Cell Transplantation

Background: Acquired von Willebrand syndrome (aVWS) is a rare bleeding disorder in children, mainly caused by congenital heart disease or pulmonary arterial hypertension. Single cases of pediatric aVWS associated with rare autoimmune diseases such as Hashimoto's thyreoiditis have been reported, all diagnosed by loss of large von Willebrand factor (VWF) multimers.

Aims: To present the clinical and laboratory findings of a boy with immune complex-mediated aVWS.

Methods: Coagulation tests, platelet count, von Willebrand Factor antigen (VWF:Ag), von Willebrand Factor Collagen Binding (VWF:CB), von Willebrand Factor activity (VWF:Akt) [Innovance®]), VWF multimer analysis and immunofixation assay were performed by standard methods.

Results: A 5-year-old boy with Wiscott-Aldrich syndrome (WAS) showed unexpected severe gastrointestinal and intraoperative bleeding after allogeneic hematopoietic stem cell transplantation (allo-HSCT) and Hemoglobin-relevant bleeding after port needle removal. Extended laboratory diagnostics showed normal or even elevated levels of all coagulation factors including VWF (VWF:Akt > 400%). VWF multimer analysis was normal. Since the boy had several immunological problems, including graft-versus-host disease, we discussed the possibility of an immune complex-mediated aVWS. Therefore we performed an immunofixation assay, which showed an α-heavy chain. VWF multimer analysis at low dilution of 1:5, then showed a distorted band structure, indicating the presence of monoclonal IgA, forming immune complexes with VWF, resulting in aVWS.

Conclusion(s): To our knowledge, there are no reports of immune complex-mediated aVWS in children. In adults only single cases have been published, usually showing monoclonal IgG or IgM. Since we have seen some patients with unexplained bleeding after allo-HSCT and normal laboratory results, including VWF multimer analysis only in standard dilution, this coagulation disorder may be underdiagnosed as missed with multimer analysis in standard dilution and should be considered specifically in children with severe immunological problems after allo-HSCT.