Clinical Spectrum and Management of Von Willebrand Disease Among Children in Assiut Governorate

Von Willebrand disease (VWD) is the most common inherited bleeding disorder worldwide and represents a significant cause of mucocutaneous bleeding in children. It results from quantitative or qualitative defects of von Willebrand factor (VWF), a glycoprotein that plays a key role in platelet adhesion and stabilization of factor VIII. VWD is classified into three main types according to International Society on Thrombosis and Hemostasis (ISTH) criteria: type 1 (partial quantitative deficiency), type 2 (qualitative defects with several subtypes), and type 3 (severe quantitative deficiency).

The clinical presentation of VWD in children is highly variable and may include epistaxis, easy bruising, gingival bleeding, prolonged bleeding after minor trauma or surgery, and menorrhagia in adolescent females. The severity and frequency of bleeding episodes are influenced by disease subtype, VWF levels, age, and associated conditions. In pediatric populations, diagnosis may be delayed or missed due to mild symptoms, age-related physiological variations in VWF levels, and limited awareness.

This study is designed as a descriptive retrospective-prospective observational study conducted at Assiut University Children's Hospital. The target population includes children aged 0-18 years with suspected or confirmed von Willebrand disease who are residents of Assiut Governorate or receive care at the study center. Patients with other inherited or acquired bleeding disorders will be excluded.

During the retrospective phase, medical records of previously diagnosed VWD patients will be reviewed to collect demographic data, family history, clinical presentation, laboratory findings, disease subtype, treatment received, and documented outcomes. In the prospective phase, children presenting with bleeding symptoms suggestive of VWD will undergo standardized clinical assessment, including a structured bleeding questionnaire and physical examination, followed by laboratory evaluation.

Laboratory investigations will include complete blood count, coagulation profile, VWF antigen level, VWF activity, and factor VIII activity, with additional specialized testing when available. Disease classification will be performed according to ISTH guidelines.

Management data will be collected to describe current treatment practices, including on-demand therapy during bleeding episodes and prophylactic therapy for patients with recurrent or severe bleeding. Treatment response, frequency of bleeding episodes, need for hospital visits, and occurrence of adverse events will be monitored during follow-up.

The primary outcomes of the study include the frequency of von Willebrand disease among the investigated pediatric population, distribution of disease subtypes, and characterization of clinical bleeding patterns. Secondary outcomes include assessment of treatment modalities, recurrence of bleeding episodes, and short-term clinical outcomes.

By providing comprehensive data on the clinical spectrum and management of VWD among children in Assiut Governorate, this study aims to enhance early diagnosis, guide evidence-based management strategies, and improve overall patient care in this setting.

Inclusion criteria

• Age 0-18 years.
• Residents of Assiut Governorate or receiving care at Assiut University Children's Hospital.
• Suspected or confirmed von Willebrand disease (VWD) based on clinical bleeding symptoms or referral for evaluation.
• Patients diagnosed with VWD using standard laboratory tests, including:
• VWF antigen (VWF:Ag).
• VWF ristocetin cofactor activity (VWF:RCo).
• Factor VIII activity.

Exclusion criteria

• Other inherited bleeding disorders, such as:
• Hemophilia A or B.
• Rare coagulation factor deficiencies (e.g., factors I, V, VII, X, XI deficiency).
• Platelet function disorders.
• Acquired bleeding disorders, including:

• Liver disease.
• Renal insufficiency.
• Vitamin K deficiency.
• Disseminated intravascular coagulation (DIC).
• Use of medications that may interfere with coagulation testing (e.g., anticoagulants, antiplatelet drugs).
• Incomplete clinical or laboratory data (for retrospective cases).
• Refusal of consent for participation (for prospective cases).