Association of acquired von Willebrand syndrome with AL amyloidosis

Abstract

Acquired loss of functional von Willebrand factor (VWF) has been termed the acquired von Willebrand syndrome (AVWS). AVWS is a rare adult-onset bleeding diathesis that is clinically similar to congenital von Willebrand disease (VWD), and occurs with a variety of autoimmune, lymphoproliferative, or myeloproliferative disorders. We have identified four patients with AVWS in association with immunoglobulin light chain (AL) amyloidosis. These patients, lacking any pre-existing or family history of abnormal bleeding, developed cutaneous, mucosal, or gastrointestinal bleeding in the course of their disease without deficiency of clotting factor X or other factors; the activated partial thromboplastin time (aPTT) was prolonged in three out of the four cases. Despite normal VWF antigen levels, VWF ristocetin cofactor activity (VWF:RCo) was low. Electrophoresis patterns of high molecular weight (HMW) VWF multimers were abnormal in two of the four cases. Two of the patients were treated with high-dose intravenous melphalan followed by autologous stem cell transplantation (HDM/SCT) and achieved hematologic remission. In these two patients, the bleeding diathesis improved and the coagulation parameters normalized, confirming a causal relationship between the plasma cell dyscrasia and the AVWS. AVWS should be considered in AL amyloidosis patients with hemorrhagic diatheses and normal clotting factor levels.

Amyloidosis of the liver on shear wave elastography: case report and review of literature

“…Gertz et al reported bleeding risk after liver biopsy in patients with amyloidosis in 2% [35] of cases, while Park et al [34] reported bleeding in as many as 4% of patients. The increased risk of bleeding after liver biopsy in patients with hepatic amyloidosis has been attributed to a number of factors: (1) reduced synthesis and/or malabsorption of vitamin K-dependent clotting factors resulting in coagulopathy, (2) amyloid fibrils bind with factor X and are rapidly cleared from the system, resulting in a deficiency of factor X, and (3) decreased contractility of amyloid infiltrated vessels, which, once lacerated, may not clot normally [36][37][38][39]. Given the potentially higher risk of bleeding in patients with amyloidosis, a non-invasive imaging modality that can aid in the diagnosis of hepatic amyloidosis could be very helpful.…”

Coagulopathy in a patient with nephrotic syndrome

“…However, neither INR nor aPTT correlated well with the factor X levels [5]. Deficiencies of other coagulation factor deficiencies may coincide; these include factor IX deficiency [14], factor XII deficiency [15], von Willebrand factor deficiency [16], and factor V deficiency [17].…”

Risk factors for venous thromboembolism in immunoglobulin light chain amyloidosis

“…[1][2][3][4][5] The predilection for bleeding complications has been attributed to acquired factor X deficiency, acquired von Willebrand syndrome, and vascular fragility due to amyloid fibril deposition in small capillaries. 2,4,[6][7][8][9] The last is primarily responsible for the periorbital ecchymoses considered pathognomonic of the disease. The etiology, risk, and optimal management of thrombotic complications in AL have not been established.…”