ristocetin and Paraproteinemias

Acquired von Willebrand syndrome (AVWS) usually mimics von Willebrand disease (VWD) type 1 or 2A. However, in rare cases, the characteristics of other VWD types can predominate in AVWS that might require careful consideration of differential treatment options. The diagnosis and the treatment of a case of type 2B-like AVWS are discussed. Diagnosis of AVWS was ascertained by determining ristocetin cofactor activity, ristocetin-induced platelet aggregation, von Willebrand factor antigen, collagen binding and characterization of von Willebrand factor (VWF) multimers. Inhibitor presence was sought through mixing experiments, the Bethesda method, and calculation of the in-vivo recovery and plasma half-life of VWF after administration of factor VIII/VWF concentrate. Mutations in the A1 domain of VWF were ruled out by sequencing of exon 28 of the VWF gene. A 34-year-old male patient, putatively diagnosed with type 2B VWD, and undergoing laparoscopic cholecystectomy, did not respond adequately to perioperative hemostatic treatment with desmopressin and high doses of factor VIII/VWF concentrate, requiring the administration of recombinant activated factor VII. Further diagnostic workup revealed AVWS mimicking type 2B VWD, most likely owing to an autoantibody developed in the course of underlying monoclonal gammopathy of undetermined significance. The presence of AVWS should be considered before a diagnosis of type 2B VWD is made, especially in patients with a history atypical for inherited disease.

Topics: Adult; Autoantibodies; Bleeding Time; Cholecystectomy, Laparoscopic; Collagen; Deamino Arginine Vasopressin; Diagnosis, Differential; Exons; Factor VII; Factor VIII; Humans; Male; Paraproteinemias; Platelet Aggregation; Protein Binding; Recombinant Proteins; Ristocetin; Sequence Analysis; Syndrome; von Willebrand Disease, Type 2; von Willebrand Factor