Symptoms in Infants and Toddlers With von Willebrand Disease

Abstract

Source: Dupervil B, Abe K, O’Brien SH, et al. Characteristics, complications, and sites of bleeding among infants and toddlers less than 2 years of age with VWD. Blood Adv. 2021;5(8):2079-2086; doi:10.1182/bloodadvances.2020004141Investigators from multiple institutions conducted a retrospective study to describe the diagnosis and bleeding history among infants and toddlers with von Willebrand disease (VWD). For the study, data from the CDC Universal Data Collection (UDC) surveillance system established in the US Hemophilia Treatment Center (HTC) Network were reviewed. Children <24 months old, diagnosed with VWD and treated at one of 135 HTCs from 2003 to 2011 were enrolled. For the UDC, data on demographics, VWD diagnosis, family history of bleeding disorders, and history and treatment of bleeding episodes were collected at enrollment and regularly scheduled visits in a systematic manner. VWD type (1, 2, or 3) was classified based on the diagnosis made by the treating physician at the HTC. Descriptive statistics were used to characterize demographics, age at diagnosis, reason for diagnosis (family history or unusual bleeding), and number and anatomic location of bleeding episodes. Chi-square, Fisher exact, or Wilcoxon rank sum tests were used to assess differences when groups were compared.Data on 105 infant and toddlers were analyzed. The mean age of enrollment was 14 months, and 61 (58%) of the patients were male. Among these infants and toddlers, 63% had VWD type 1, 28% type 2, and 9% type 3. There was a family history of bleeding disorders in 79.1%. A family history of VWD prompted diagnostic testing in 68% of study patients; 93% of children diagnosed with type 2 disease had a family history of VWD, compared to 77% of those with type 1 and 44% of those with type 3 (P = 0.02). The mean age at diagnosis of all study patients was 7 months. Children with type 2 VWD were diagnosed at a significantly younger age than those with types 1 and 3 (mean age, 4.7, 8.0, and 6.8 months, respectively; P = 0.04).Among study participants, 22% experienced a bleeding episode before the diagnosis of VWD, 22% were diagnosed at the time of an episode, and approximately 50% were diagnosed before their first notable bleeding event (with testing done because of a family history). Overall, 274 bleeding events were documented in 73 patients. The most common types of bleeding episodes were oral/nasal bleeds (166 episodes, 60.6%) and soft-tissue hematomas (57 episodes, 20.8%); 9 boys (14.8%) experienced unusual bleeding with circumcision. There were 7 episodes of subdural hemorrhages among the study children, occurring both after trauma and spontaneously.The authors conclude that the majority of infants and toddlers with VWD have a family history of the disease, and bleeding episodes are common.Dr Hogan has disclosed no financial relationship relevant to this commentary. This commentary does not contain a discussion of an unapproved/investigative use of a commercial product/device.Von Willebrand disease affects up to 1% of the U.S. population.1 Von Willedbrand Factor (VWF) is an acute-phase reactive glycoprotein that aggregates and adheres platelets to damaged blood vessel walls.2 Many with Type 1 VWD, a partial VWF deficiency associated with autosomal dominant inheritance, are unaware of their bleeding disorder due to mild gum bleeding, epistaxis, petechiae, bruising, gastrointestinal bleeding, and heavy menses often attributable to co-morbidities, medications, or trauma (See AAP Grand Rounds. 2020;44[5]:54.)3 Those with subtypes of type 2 VWD, due to different qualitative VWF defects, have variable inheritance and bleeding symptoms.4 Those with the rarest, type 3 VWD, due to an autosomal recessive inheritance manifesting with an absence of VWF, have severe bleeding symptoms.4In older children, teens, and adults, screening for bleeding disorders includes family history and symptom scores using the International Society on Thrombosis and Haemostasis Bleeding Assessment Tool.5 Falsely abnormal or normal blood test results for CBC, PT, PTT, VWF antigen, VWF activity, Factor VIII, and multimeric analysis arise due to issues with phlebotomy, specimen handling, and assay variability.6 Interpretation of diagnostic test results are affected by blood type, hormones, and concurrent stressors such as fear, exercise, or infection.2 Currently, complex genetic testing plays a limited role in diagnosis and clinical severity in some type 2 VWD cases.7The current investigators review a large cohort of newborns, infants, and toddlers with VWD and describe bleeding episodes, which occur most often before 1 year of age. Limitations of this study include overrepresentation of non-Hispanic whites and missing data for bleeding characteristics or scores, VWF antigen/activity levels, and vitamin K administration at birth. No control cohort with or without bleeding symptoms was available for comparison.A family history of VWD or personal history of oropharyngeal, circumcision-related, hematomas, or intracranial bleeds in children <2 years of age indicate the need for evaluation for VWD.