Pediatr Blood Cancer 2009;53:655–657 BRIEF REPORT Transient Neonatal Acquired von Willebrand Syndrome Due to Transplacental Transfer of Maternal Monoclonal Antibodies Amulya A. Nageswara Rao, MD, 1 Vilmarie Rodriguez, MD, 1,2 Margaret E. Long, MD, 3 Jeffrey L. Winters, MD, 4 William L. Nichols, MD, 2,5 and Rajiv K. Pruthi, MBBS 2,5 * INTRODUCTION With a prevalence of upto 1% of the general population, congenital von Willebrand disease (CVWD) is the most common hereditary bleeding disorder [1] whereas acquired von Willebrand syndrome (AVWS) has an estimated prevalence of 0.04% [2]. Since its initial description in 1968 in a young boy with systemic lupus erythematosus [3], there have been an increasing number of reports [4] of AVWS in the pediatric population, described in association with various underlying disorders. Since AVWS is most often seen in the elderly, with a median age at diagnosis of 62 years [2], younger patients may escape accurate diagnosis. Herein we report the first case of a transient neonatal AVWS in a child born to a 31-year-old woman who was initially diagnosed with CVWD, but was later found to have AVWS in association with monoclonal gammopathy of undetermined significance (MGUS). We present the peripartum management and natural history of the AVWS in the neonate. CASE REPORT A 31-year-old gravida 2, para 1 was referred at 38 3 = 7 weeks of gestation for peripartum management of presumptive CVWD. Her history was significant for a tonsillectomy at age 8 years, a motor vehicle accident requiring 16 sutures for a hand injury, and a normal spontaneous vaginal delivery at 19 years of age, all of which were hemostatically uneventful. Five years later, she was diagnosed with VWD at another institution, following testing for prolonged bleeding after dental extraction. Her parents and daughter were also tested and found to be normal, and although her only brother was not tested, he had no bleeding symptoms. She experienced no further spontaneous bleeding and did not have any follow-up until her current pregnancy. Her prenatal course was significant for increased bleeding of gums, easy bruisability, and gestational diabetes controlled by oral hypoglycemics. At her local hospital, a therapeutic trial with von Willebrand factor (VWF) concentrate (dose unknown) was performed, with no significant increase in 1 hr post-infusion VWF levels and she was referred to our institution for management of labor and delivery. Laboratory evaluation done at our institution demonstrated a normal complete blood count and prothrombin time, and mixing study corrected the mildly prolonged activated partial thrombo- plastin time (APTT) from 40 to 31 sec (normal range 21 – 33 sec). Additional testing demonstrated decreased VWF antigen (VWF:Ag: 19%; ref range 55–200%), VWF ristocetin cofactor activity (VWF:RCo: <12%; ref range 55–200%), and coagulation factor VIII activity (FVIII:C: 14%; ref range 55–205%). Plasma VWF multimer analysis demonstrated substantially decreased VWF antigen, but no definite loss of the high and intermediate molecular weight multimers, consistent either with congenital type 1 VWD or AVWS. VWF inhibitor screen was negative (no inhibition of VWF:RCo activity by a 4:1 mixture of patient and normal plasma incubated 1 hr). Intravenous administration of VWF/ FVIII concentrate [Humate-P 6,000 U; body weight 110 kg] demonstrated no significant post-infusion increase in VWF or FVIII (Fig. 1). An AVWS was suspected given her acquired onset of bleeding disorder, markedly shortened half-life of the infused Humate-P and normal thyroid stimulating hormone level. Mono- clonal protein studies demonstrated a monoclonal IgG kappa serum protein (0.7 g/dl) suggesting presence of a non-neutralizing antibody reactive with VWF. On the morning of the planned Cesarean delivery she underwent one plasma volume exchange performed using the COBE Spectra (CaridianBCT, Lakewood, CO) with 5% normal serum albumin replacement for the first half and fresh frozen plasma for the second half with ACD-A as anticoagulant. This was done to replace coagulation factors and avoid systemic anticoagulation prior to the planned surgical procedure. Following that, she received a bolus of Humate-P (15,000 U), followed by a continuous infusion (1,500 U/ hr) and intravenous immunoglobulin [IVIG (Carimune)] (0.5 g/kg). Although typically a disorder of adults, acquired von Willebrand syndrome (AVWS) is increasingly being recognized in the pediatric population in association with congenital cardiac diseases, certain neoplasia, and hypothyroidism. Transplacental transfer of maternal immunoglobulin G (IgG) antibodies as a cause of neonatal disorders in infants born to mothers with autoimmune conditions has been reported. We describe the diagnosis and peripartum clinical management of AVWS due to monoclonal gammopathy of undetermined significance (MGUS) and the first reported case of transient neonatal AVWS due to transplacental transfer of maternal IgG antibodies. Pediatr Blood Cancer 2009;53: 655–657. ß 2009 Wiley-Liss, Inc. Key words: acquired von Willebrand syndrome; monoclonal gammopathy; peripartum management; transplacental antibody transfer ß 2009 Wiley-Liss, Inc. DOI 10.1002/pbc.22084 Published online 20 May 2009 in Wiley InterScience (www.interscience.wiley.com) —————— 1 Division of Pediatric Hematology/Oncology, Mayo Clinic, Rochester, Minnesota; 2 Comprehensive Hemophilia Center, Division of Hematology, Mayo Clinic, Rochester, Minnesota; 3 Department of Obstetrics and Gynecology, Mayo Clinic, Rochester, Minnesota; 4 Division of Transfusion Medicine, Mayo Clinic, Rochester, Minnesota; 5 Special Coagulation Laboratory, Division of Hematopathology, Mayo Clinic, Rochester, Minnesota *Correspondence to: Rajiv K. Pruthi, Mayo Clinic, 200 First Street SW, Rochester, MN 55905. E-mail: pruthi.rajiv@mayo.edu Received 16 February 2009; Accepted 3 April 2009