Acquired von Willebrand syndrome: transplacental transfer of maternal monoclonal antibodies and description of peripartum management

Objective: To describe the diagnosis and peripartum clinical management of acquired von Willebrand syndrome (AVWS) due to monoclonal gammopathy of undetermined significance (MGUS) and development of neonatal AVWS due to transplacental transfer of monoclonal maternal IgG antibodies. Methods: Case report and literature review. Summary: A 31-year-old female, with no prior personal spontaneous or surgical bleeding and no family history of bleeding, was diagnosed as having von Willebrand's disease (VWD) in 2000 after prolonged bleeding following dental extraction. In 2007, while pregnant, she underwent a therapeutic trial of Humate-P® concentrate in anticipation of labour and delivery. Markedly accelerated clearance of infused von Willebrand factor (VWF) was noted, and she was referred to Mayo Clinic for peripartum management. Her baseline plasma VWF: Ag, VWF: RCo, and FVIII were 25%, <12% and 13% respectively. Plasma VWF multimer analysis demonstrated loss of the high and intermediate molecular weight multimers. The VWF inhibitor screen was negative (no inhibition of VWF: RCo activity by a 4:1 mixture of patient and normal plasma incubated 1 h). Identification of a monoclonal IgG kappa serum protein (0.7 gm dL−1) suggested presence of a non-neutralizing antibody reactive with VWF. Prior to delivery of the neonate by caesarean section she underwent preoperative plasma exchange and infusion of immune globulin (IVIG), followed by bolus and continuous infusion of Humate-P concentrate, and normal or elevated plasma levels of VWF and FVIII were repeatedly observed during the next 5 days. Operative blood loss was estimated at 1L, but erythrocyte transfusion was not required and there was no subsequent abnormal maternal bleeding. Although there was no clinical neonatal bleeding, testing of the neonate demonstrated presence of monoclonal IgG kappa protein and low VWF: Ag, VWF: RCo and FVIII (34%, 14% and 9% respectively). Follow-up testing showed clearance of the monoclonal protein at 26 weeks of age. Conclusions: In contrast to congenital von Willebrand's disease (VWD), AVWS is rarer with an estimated prevalence of up to 0.04% in the general population. Like VWD it is characterized by mucocutaneous and postoperative bleeding due to defective VWF. However, there is no personal or family history and there is usually an underlying pathogenetically linked disease. Immune-mediated accelerated clearance of plasma VWF is one of the postulated pathogenic mechanisms making it both a diagnostic and therapeutic challenge. Medline search of English literature from 1968–2007 showed only one other case report describing the peripartum management of AVWS. Although AVWS has been described in infancy and early childhood, our report is the first to describe transplacentally acquired neonatal AVWS. Management of pregnant women with AVWS and suspected or proven antibodies to VWF should include testing of the newborn while avoiding invasive and elective surgical procedures until haemostasis is demonstrated to be normal. Plasma exchange and IVIG, coupled with Humate-P infusion, temporarily ameliorated maternal AVWS associated with IgG MGUS.