Bleeding spectrum in children with moderate or severe von Willebrand disease: Relevance of pediatric‐specific bleeding

Abstract

The bleeding phenotype of children with von Willebrand disease (VWD) needs to be characterized in detail to facilitate diagnosis during childhood and aid in the planning and assessment of treatment strategies. The objective was to evaluate the occurrence, type, and severity of bleeding in a large cohort of children with moderate and severe VWD. We included 113 children (aged 0-16 years) with Type 1 (n 5 60), 2 (n 5 44), and 3 (n 5 9) VWD with von Willebrand factor (VWF) antigen and/or VWF ristocetin cofactor levels 30 U/dL from a nation-wide cross-sectional study ("Willebrand in the Netherlands" study). Bleeding severity and frequency were determined using the International Society on Thrombosis and Hemostasis-Bleeding Assessment Tool (ISTH-BAT) with supplementary pediatric-specific bleeding symptoms (umbilical stump bleeding, cephalohematoma, cheek hematoma, conjunctival bleeding, postcircumcision and postvenipuncture bleeding). We found that all 26 postmenarche girls experienced menorrhagia. Other common bleedings were cutaneous (81%), oropharyngeal (64%), prolonged bleeding from minor wounds (58%), and epistaxis (56%). Pediatric-specific bleeding symptoms were present in 44% of patients. ISTH-BAT bleeding score was higher in index cases than in affected family members (median, 12.0 vs. 6.5, P < 0.001), higher in Type 3 VWD than in Type 2 or 1 (17.0 vs. 10.5 or 6.5, P < 0.001) and higher in children with severe (<10 U/dL) than moderate VWD (10-30 U/dL) (11.0 vs. 7.0, P < 0.001). Frequency of any bleeding, epistaxis, and oral cavity was higher in types 2 and 3 than in Type 1 VWD and was associated with VWF levels. We conclude that pediatric-specific bleeding symptoms occurred in a large proportion of children with moderate or severe VWD and should be included when evaluating children for VWD.

A 1½ year old girl with excessive bleeding following accidental trauma to the upper labial frenum during playing

“…It develops by a variety of mechanisms in such acquired disorders but typically resolves with the treatment of the underlying disease or cause. 63 Several factors influence the symptoms of Von Willebrand disease: Plasma level of residual Von Willebrand factor activity, disease type and subtype and also age and sex of the patient. Bruising and epistaxis are the prominent symptoms in children with Von Willebrand disease.…”

Advances in the diagnosis and treatment of Von Willebrand disease

“…Type 3 patients have the highest bleeding scores, type 2 patients are intermediate, and type 1 patients have the lowest bleeding scores. 9 In addition, lower VWF:Ag and FVIII have been associated with increased bleeding scores. 10 However, obtaining a bleeding score on a patient who has previously been diagnosed and received treatment may be difficult, as treatment in and of itself will raise the bleeding score.…”

“…Inclusion of pediatric-specific questions may be helpful but does not always provide complete reassurance that a given patient will not develop bleeding in the future. 9 In addition, some studies are complicated by the fact that bleeding scores rely on the worst historical episode to generate points; a patient who receives a diagnosis of VWD and is subsequently treated for surgery can generate an increased bleeding score independent of their recent symptoms because of that treatment. Because VWF levels increase with age, 12 it is possible that a patient might "outgrow" their diagnosis.…”

Sports participation and physical activity in patients with von Willebrand disease

“…VWD is caused by reduced von Willebrand factor (VWF) levels (type 1), an abnormal function of VWF (type 2) or a complete absence of VWF (type 3) . Although VWD is clinically mainly characterized by mucocutaneous bleeding, all types of bleeding can occur . We previously found that adults and children with VWD have a lower health‐related quality of life (HRQoL) compared to the general population .…”