Thromb Haemost 2020; 120(03): 457-465
DOI: 10.1055/s-0040-1701239
Cellular Haemostasis and Platelets
Georg Thieme Verlag KG Stuttgart · New York

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

Anna Ruiz-Llobet
1  Department of Pediatric Hematology, Hospital Sant Joan de Déu de Barcelona, Universitat de Barcelona, Barcelona, Spain
2  Institut de Recerca Hospital Sant Joan de Déu de Barcelona (IRP-HSJD), Barcelona, Spain
,
Ignacio Isola
3  Department of Laboratory, Hematology, Hospital Sant Joan de Déu de Barcelona, Universitat de Barcelona, Barcelona, Spain
4  Department of Pathology, CDB, Hospital Clínic de Barcelona, IDIBAPS, Universitat de Barcelona, Barcelona, Spain
,
Susanna Gassiot
1  Department of Pediatric Hematology, Hospital Sant Joan de Déu de Barcelona, Universitat de Barcelona, Barcelona, Spain
3  Department of Laboratory, Hematology, Hospital Sant Joan de Déu de Barcelona, Universitat de Barcelona, Barcelona, Spain
,
Albert Català
1  Department of Pediatric Hematology, Hospital Sant Joan de Déu de Barcelona, Universitat de Barcelona, Barcelona, Spain
2  Institut de Recerca Hospital Sant Joan de Déu de Barcelona (IRP-HSJD), Barcelona, Spain
5  Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBER ER), Instituto de Salud Carlos III, Madrid, Spain
,
Maribel Díaz-Ricart
4  Department of Pathology, CDB, Hospital Clínic de Barcelona, IDIBAPS, Universitat de Barcelona, Barcelona, Spain
,
Antonio F. Martínez-Monseny
1  Department of Pediatric Hematology, Hospital Sant Joan de Déu de Barcelona, Universitat de Barcelona, Barcelona, Spain
6  Genetics and Molecular Medicine Department and Pediatric Institute of Rare Diseases (IPER), CIBERER U-703, Hospital Sant Joan de Déu, Barcelona, Spain
,
Mercedes Serrano
1  Department of Pediatric Hematology, Hospital Sant Joan de Déu de Barcelona, Universitat de Barcelona, Barcelona, Spain
7  Department of Pediatric Neurology, U-703 CIBERER, Hospital Sant Joan de Déu, Barcelona, Spain
,
Rubén Berrueco
1  Department of Pediatric Hematology, Hospital Sant Joan de Déu de Barcelona, Universitat de Barcelona, Barcelona, Spain
2  Institut de Recerca Hospital Sant Joan de Déu de Barcelona (IRP-HSJD), Barcelona, Spain
5  Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBER ER), Instituto de Salud Carlos III, Madrid, Spain
› Author Affiliations
Further Information

Publication History

15 July 2019

12 December 2019

Publication Date:
05 March 2020 (online)

Abstract

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.

Supplementary Material