TY - JOUR AU - Ruiz-Llobet, Anna; Isola, Ignacio; Gassiot, Susanna; Català, Albert; Díaz-Ricart, Maribel; Martínez-Monseny, Antonio F.; Serrano, Mercedes; Berrueco, Rubén TI - Platelet Dysfunction in Noonan and 22q11.2 Deletion Syndromes in Childhood SN - 0340-6245 SN - 2567-689X PY - 2020 JO - Thromb Haemost JF - Thrombosis and Haemostasis LA - EN VL - 120 IS - 03 SP - 457 EP - 465 DA - 2020/03/05 KW - thrombocytopathy KW - DiGeorge syndrome KW - 22q11.2 deletion syndrome KW - noonan syndrome KW - childhood KW - pediatrics AB - 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 (n = 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 (p = 0.049, p = 0.043) and epinephrine (p = 0.021, p = 0.035), and ADP (p = 0.117, p = 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 (p = 0.034) and collagen/ADP (p = 0.01). A significant association between ISTH-BAT score >3 and closure times (p = 0.022, p = 0.002) and aggregation defect with ristocetin (p = 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. PB - Georg Thieme Verlag KG DO - 10.1055/s-0040-1701239 UR - http://www.thieme-connect.com/products/ejournals/abstract/10.1055/s-0040-1701239 ER -