Same Syndrome, Different Causes and Treatment: Path to Diagnosis and Management of Two Interesting Cases of Acquired von Willebrand Syndrome

von Willebrand disease (VWD) is considered the most common inherited bleeding disorder with a population prevalence of 0.6 to 1.3%.[1] [2] [3] Affected patients have a personal and family history of mucocutaneous hemorrhage and abnormal bleeding after surgery or trauma. These clinical features, in combination with evidence of quantitative and/or qualitative defects of von Willebrand factor (VWF), are considered diagnostic for the disease. VWF is a multimeric glycoprotein synthesized by endothelial cells and megakaryocytes that promotes platelet adhesion and aggregation and acts as a carrier for factor VIII protecting it from rapid degradation.[4] Acquired von Willebrand syndrome (AVWS) is a rare bleeding disorder with clinical and laboratory features similar to congenital VWD but without personal and family history of bleeding. Moreover, unlike acquired hemophilia, which is attributable to neutralizing autoantibodies against coagulation factors, several different mechanisms linked to underlying diseases are involved in AVWS.[3] If VWF is normally synthesized, one of four pathogenetic mechanisms might be involved: (1) specific autoantibodies that inactive VWF; (2) nonspecific antibodies that form circulating immune complexes with VWF, with these then rapidly cleared by Fc-R bearing cells; (3) absorption of VWF into surface of neoplastic cells via an aberrant or a constitutive expression of glycoprotein Ib (GpIb)/IX; (4) increased proteolytic degradation of high molecular weight VWF multimers under conditions of shear stress or by ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13) enzyme. Often, more than one pathogenetic mechanism coexists.[5]