Evaluation of Bleeding Symptoms in Children with An Inherited Mucocutaneous Bleeding Disorder.
Authors: Biss Tina T. , Blanchette Victor S. , Clark Dewi S. , Wakefield Cindy D. , Silva Mariana , James Paula D. , Rand Margaret L. 
Published: October 2019

Abstract
Abstract 1292
Poster Board I-314

Introduction
Accurate assessment of bleeding symptoms is an essential step in the diagnosis of an inherited mucocutaneous bleeding disorder (IMBD). This is difficult in childhood when symptoms such as bruising and epistaxis are frequently noted in normal children. In addition, children may not have been exposed to hemostatic challenges such assurgery, dental extraction and menarche. Knowledge of the spectrum of presenting features of an IMBD may aid diagnosis. The MCMDM-1 VWD Bleeding Questionnaire, which uses a symptom-specific grade of -1 to 4 (Tosetto et al., J Thromb Haemost 2006:4;766), was recently modified for use in a pediatric population by inclusion of questions related to pediatric-specific bleeding symptoms. The Pediatric Bleeding Questionnaire (PBQ) has been validated in the assessment of bleeding symptoms in children and a score of 2 or greater predicts a diagnosis of VWD (Bowman et al., J Thromb Haemost 2009; doi:10.1111/j.1538-7836.2009.03499.x). This present study applied the PBQ to a cohort of children with a prior diagnosis of an IMBD in order to evaluate the prevalence and severity of specific bleeding symptoms.

Patients and Methods
The PBQ was used to determine bleeding score for 123 children with a prior diagnosis of VWD or a platelet function disorder (PFD) at The Hospital for Sick Children, Toronto, or Kingston General Hospital, Kingston, by interview of parents/children. A clinically-significant bleeding symptom was defined as one severe enough to require consultation with a healthcare professional, medical/surgical intervention or blood transfusion.

Results
100 children had a diagnosis of VWD and 23, a PFD (Glanzmann thrombasthenia: 4; dense granule deficiency: 9; MYH9-related disease: 3; Noonan syndrome: 2; Ehlers-Danlos syndrome: 2; undefined PFD: 3). 65 were male and 58 female with a median age of 10.7 years (range: 0.6-18). Mean bleeding score was 8.3 for the entire cohort (range: 0-29) and varied between diagnostic groups (definite type 1 VWD: 9.5 (range: 2-18); possible type 1 VWD: 3.0 (range: 0-15); type 2 VWD: 11.8 (range: 3-17); type 3 VWD: 14.6 (range: 4-29); PFD: 9.5 (range: 1-20). The prevalence of each of the bleeding symptoms is shown in Table 1. The most frequent clinically-significant bleeding symptoms in the cohort were: menorrhagia, 57% (of menstruating females); epistaxis, 36%; prolonged bleeding from minor wounds, 35%; and bleeding after tooth extraction, 30%. The most frequent clinically-significant bleeding symptoms did not vary greatly between each of the diagnostic groups but oral cavity bleeding, hemarthrosis, gastrointestinal bleeding and hematoma were more frequent in children with type 3 VWD. All symptoms were less frequent in children with possible type 1 VWD. Menorrhagia was a prevalent symptom in menstruating females in all diagnostic groups. Clinically-significant pediatric-specific bleeding symptoms were seen in 20% of children. The most frequent were: post-circumcision bleeding, 35% (of circumcised males); cephalohematoma, 7%; macroscopic hematuria, 4%; and umbilical stump bleeding, 3%. These symptoms occurred most frequently in children with type 3 VWD, type 2 VWD or PFD.

Conclusions
Children with an IMBD frequently report menorrhagia, epistaxis, prolonged bleeding from minor wounds and bleeding after tooth extraction. Pediatric-specific bleeding symptoms also occur. There are differences in prevalence of symptoms between subtypes of VWD and PFDs. This information can assist the evaluation of children with bleeding symptoms.

Disclosures
No relevant conflicts of interest to declare.