Association of Acquired Von Willebrand Syndrome with Primary (AL) Amyloidosis.

Easy bruising is a common clinical symptom in primary (AL) amyloidosis, and can occur through multiple mechanisms. Infiltration of amyloid fibrils into thin-walled capillaries leads to mechanical fragility predisposing to petechiae and purpura, with periorbital “raccoon-eye” purpura being pathognomonic of AL amyloidosis. Another mechanism predisposing to bleeding in AL amyloidosis is adsorption of coagulation factors to amyloid fibrils. In 1977, Furie et al. reported (New England Journal of Medicine) that elevation of the clotting times is most commonly due to deficiency of factor X, and other investigators have since reported deficiencies of factors II, V, IX, or XIII. We have demonstrated that remission of the underlying plasma cell dyscrasia after high dose melphalan chemotherapy and autologous stem cell transplantation can lead to remission of the acquired factor X deficiency (Choufani et al., Blood 2001). From 2000–2004, four amyloidosis patients presented to Boston University Medical Center with bleeding and a prolonged activated partial thromboplastin time (aPTT), but with no such factor deficiency. Instead, they were found to have abnormal von Willebrand ristocetin cofactor (vWF:RCo) and/or factor VIII (FVIII:C) activities, with normal vWF antigen (vWF:Ag), consistent with a functional defect in von Willebrand factor (vWF). None of the patients had a prior history or family history consistent with congenital von Willebrand’s disease, thus they were diagnosed with acquired von Willebrand syndrome (AvWS). AvWS has most often been reported in association with other lymphoproliferative or myeloproliferative disorders. The aPTT was prolonged in three out of the four cases. Loss of high molecular weight multimers (HMWM) was observed in two of the four cases. Two of the patients were treated with high-dose intravenous melphalan followed by autologous stem cell transplantation and achieved remission of their underlying plasma cell disease; in addition, the bleeding diathesis ceased and the coagulation parameters normalized, indicating reversal of the AvWS with effective treatment of AL amyloidosis.