Platelet Dysfunction in Noonan and 22q11.2 Deletion Syndromes in Childhood.

Introduction:  An underlying thrombocytopathy seems to be responsible for hemorrhagic symptoms in patients diagnosed with 22q11.2 deletion syndrome (22q11DS) or Noonan syndrome (NS). In 22q11DS, it is explained by a defect in the membrane glycoprotein (GP) complex Ib-V-IX. The cause of thrombocytopathy in NS remains unclear.

Aim:  The objective is to study the incidence of thrombocytopathy in pediatric patients diagnosed with 22q11DS or NS assessing the utility of ISTH-BAT questionnaire and laboratory techniques.

Materials And Methods:  Prospective study between March and December 2018 in children (2-18 years old) diagnosed with 22q11DS or NS. Hemorrhagic symptoms using ISTH-BAT score, total cell blood count, platelet indices, PFA-200 closure times, and platelet aggregation were evaluated in all patients and membrane GP expression in 22q11DS patients.

Results:  Nearly 70% of NS patients ( = 22) had a platelet aggregation defect without thrombocytopenia. A defect of platelet aggregation with adenosine diphosphate (ADP) and epinephrine was the most frequent pattern. A statistically significant inverse correlation between closure times and aggregation with arachidonic acid ( = 0.049,  = 0.043) and epinephrine ( = 0.021,  = 0.035), and ADP ( = 0.117,  = 0.05) was found. Total 5 out of 29 patients diagnosed with 22q11DS had macrothrombocytopenia; more noteworthy in older patients. Twenty-six patients showed an impairment in ristocetin-induced platelet aggregation that correlated with prolonged collagen/epinephrine ( = 0.034) and collagen/ADP ( = 0.01). A significant association between ISTH-BAT score >3 and closure times ( = 0.022,  = 0.002) and aggregation defect with ristocetin ( = 0.043) was also demonstrated.

Conclusion:  Most NS and 22q11DS patients show an impairment of platelet aggregation that correlates with closure times. In 22q11DS patients, these results were also related to hemorrhagic symptoms.