Evaluation of bleeding disorders in patients with Noonan syndrome: a systematic review

BACKGROUND: Noonan syndrome (NS) is an autosomal dominant genetic condition that has a number of clinical features, including bleeding diathesis and a number of hematological abnormalities including clotting factor deficiencies, von Willebrand disease and abnormal platelet count/function. METHODS: We evaluated the frequency/types of bleeding disorders, and associated hematological laboratory findings, in patients with NS, using published data from 1965 to 2014. RESULTS: Of 45 studies identified, 31 included data for 428 patients with NS. Of these patients, 43% had reported bleeding, 26% had no reported bleeding and no bleed data was reported for 31%. Most patients (90%) had bleeding-related laboratory test abnormalities, but only 194 (45%) had a confirmed diagnosis of a specific bleeding disorder. Abnormal laboratory tests included: prolonged prothrombin time, activated partial thromboplastin time, and other platelet-related disorders. Of the 194 patients with a confirmed diagnosis of a specific bleeding disorder, 153 (79%) had single clotting factor deficiencies, von Willebrand disease or platelet-related disorders, and 41 (21%) had multiple deficiencies including platelet-related disorders. CONCLUSION: As patients with NS can experience multiple bleeding disorders, including abnormal platelet function, clinical evaluations should be performed at diagnosis, after diagnosis, before any surgery is undertaken, and if patients become symptomatic.