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. 2025 Jul 1;36(5):142-155.
doi: 10.1097/MBC.0000000000001364. Epub 2025 May 14.

A new approach to personalized assessment of functional platelet disorders in children with inherited thrombocytopenias by flow cytometry

Dmitrii Mikhailovich Polokhov  1   2 , Anastasiya Alexandrovna Ignatova  1 , Evgeniya Alexandrovna Ponomarenko  1 , Irina Viktorovna Mersiyanova  1 , Anna Leonidovna Khoreva  1 , Aleksandr Vladimirovich Poletaev  1 , Elena Vladislavovna Raykina  1 , Galina Anatolievna Novichkova  1 , Mikhail Aleksandrovich Panteleev  1   2   3 , Pavel Aleksandrovich Zharkov  1
Affiliations

A new approach to personalized assessment of functional platelet disorders in children with inherited thrombocytopenias by flow cytometry

Dmitrii Mikhailovich Polokhov et al. Blood Coagul Fibrinolysis. .

Abstract

Inherited thrombocytopenias are variable in the count and size of platelets, which is related with the number of receptors and intracellular structure. So, the reference ranges do not allow interpretation of functional disorders, especially in macrothrombocytopenias and microthrombocytopenias. The flow cytometry diagnostic approach to use the reference values is necessary. Seventy-five pediatric patients were divided into three groups by platelet size: 25 with normothrombocytopenia ( RUNX1, ANKRD26, ETV6 , and CYCS ), 25 with microthrombocytopenia ( WAS ), 25 with macrothrombocytopenia ( MYH9, TUBB1, SLFN14 , and BSS ). Platelet size, granularity, GPIb/V/IX, GPIIb/IIIa, granules, and procoagulant platelets were analyzed at rest and after activation by a mixture of TRAP+CRP. In addition to the absolute value indicators, a calculated 'index at rest/after activation' in relative units was introduced for personalized changes assessment. The hemorrhage was assessed using a Pediatric Bleeding Questionnaire. The control consisted of 40 children. The bleeding score ranged from 0 to 20 (median of 2). Upon activation, in all groups, weakening in platelet size contraction and procoagulant platelet formation ( P ≤ 0.02) were observed. In normothrombocytopenia and microthrombocytopenia groups, increased granularity upon activation, attenuation of CD42b shedding/internalization, correlation ( r ≥ -0.65) between a decrease of procoagulant platelets less than 5% and increase of bleeding were found. Additionally, reduction of δ-granules ( P ≤ 0.01) in normothrombocytopenias, attenuation of externalization and activation of GP IIb/III, and granules release ( P ≤ 0.001) in the microthrombocytopenia were detected. The use of 'activation indexes' in relative units allowed to identify and characterize morphofunctional abnormality patterns in different platelet size thrombocytopenia groups and interpreted control values for detecting personalized patient disorders regardless of platelet size.

Keywords: bleeding; flow cytometry; inherited thrombocytopenias; next-generation sequencing; pediatric patients.

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References

    1. Balduini CL, Pecci A, Noris P. Inherited thrombocytopenias. Hamostaseologie 2012; 32:259–270.
    1. Pecci A, Balduini CL. Inherited thrombocytopenias: an updated guide for clinicians. Blood Rev 2020; 48:100784.
    1. Lambert MP, Poncz M. Michelson AD. 46 - Inherited thrombocytopenias. Platelets 4th edNew York: Academic Press; 2019. 849–861.
    1. Bury L, Falcinelli E, Gresele P. Learning the ropes of platelet count regulation: inherited thrombocytopenias. J Clin Med 2021; 10:533.
    1. Gresele P, Harrison P, Bury L, Falcinelli E, Gachet C, Hayward CP, et al. Diagnosis of suspected inherited platelet function disorders: Results of a worldwide survey. J Thromb Haemost 2014; 12:1562–1569.