RASopathies and hemostatic abnormalities: key role of platelet dysfunction

Area of Science:

• Genetics and Molecular Biology
• Hematology
• Pediatric Medicine

Background:

• Bleeding anomalies are known in Noonan syndrome but uncharacterized in molecularly confirmed RASopathies.
• RASopathies encompass a group of genetic disorders including Noonan syndrome, sharing common molecular pathways.
• Previous studies have not specifically investigated bleeding disorders in genetically confirmed RASopathy patients.

Purpose of the Study:

• To determine the frequency and types of bleeding disorders in patients with RASopathies.
• To explore associations between bleeding diathesis and laboratory findings in RASopathy patients.
• To evaluate platelet function and coagulation parameters in relation to bleeding symptoms.

Main Methods:

• Enrolled 49 individuals with genetically confirmed RASopathies and 49 age/sex-matched controls.
• Utilized the "Paediatric Bleeding Questionnaire Scoring Key" for bleeding assessment.
• Conducted laboratory screening including clotting factors, PT, PTT, and platelet function tests.

Main Results:

• Pathological bleeding scores were found in 28.5% of RASopathy patients.
• Patients with bleeding scores showed splenomegaly, prolonged aPTT, and lower levels of factors V, VII, X, and XIII.
• Abnormalities in platelet sensitivity to ristocetin, arachidonic acid, and collagen were observed.

Conclusions:

• RASopathy patients with bleeding tendencies exhibit diverse laboratory abnormalities, particularly platelet-related disorders.
• Splenomegaly may indicate qualitative platelet dysfunction in these patients.
• Comprehensive clinical assessment and close monitoring are recommended due to the lack of management consensus.