Abstract Number: PB1246
Meeting: ISTH 2022 Congress
Background: Inherited thrombocytopenias (ITs) with predisposition to MDS/AML are commonly associated with hemorrhage.
Aims: To investigate the mechanisms of platelet dysfunction in ITs and its correlation with bleeding tendency.
Methods: Pediatric patients with ITs were included in the study. Bleeding severity was assessed with PBQ score. Aggregometry (LTA for PRP) and flow cytometry were performed to study platelet responsiveness. Healthy age-matched children were used as controls. Data were analyzed using Mann-Whitney U and Spearman correlation tests.
Results: 23 patients with germline RUNX1 (n=14), ANKRD26 (n=8), and ETV6 (n=1) mutations were included in the study. All patients had mild to moderate thrombocytopenia (Figure 1).
In patients with RUNX1 and ANKRD26 mutations, we observed diminished platelet aggregation upon stimulation with epinephrine, PAR1-AP (no secondary wave for RUNX1), collagen (only RUNX1), ADP (only ANKRD26).
In patients with RUNX1 mutations, flow cytometry revealed reduced dense granule content and diminished platelet necrosis after double stimulation with CRP and PAR1-AP. In patients with ANKRD26 and ETV6 mutations, we observed impaired GPIb shedding. Total GPIIb/IIIa density on activated platelets was increased in patients with ANKRD26 and decreased in the patient with ETV6 mutation.
We observed increased quiescent platelet cytosolic calcium concentration in patients with RUNX1 and ANKRD26 mutations. Impaired calcium mobilization and diminished fibrinogen binding upon stimulation with ADP or PAR1-AP were also observed.
We found no correlation between platelet count and bleeding in patients with RUNX1 mutations. However, we observed strong correlations between PBQ score, percentage of necrotic platelets (r = -0.64, p = 0.02) and GPIb expression (r = -0.63, p = 0.02) upon stimulation.
Conclusion(s): Platelet functional abnormalities are different in patients with ITs, and significantly correlate with bleeding. These findings emphasize the role of flow cytometry in diagnosis of these rare disorders and evaluation the prognosis of hemorrhage. The study was supported by Russian Science Foundation grant 21-74-20087.
Figure 1. Platelet function in patients with RUNX1, ANKRD26, or ETV6 mutations, and healthy children -in resting state and upon dual stimulation with CRP and PAR1-AP mixture- assessed by flow cytometry.
To cite this abstract in AMA style:Tesakov I, Fedorova D, Ovsyannikova G, Martyanov A, Ignatova A, Ponomarenko E, Pavlova A, Raykina E, Zharkov P, Smetanina N, Panteleev M, Sveshnikova A. Platelet Dysfunction in Inherited Thrombocytopenias with Predisposition to Hematologic Malignancies and its Correlation with Bleeding: Analysis of 23 Patients with RUNX1, ANKRD26, and EVT6 Mutations [abstract]. https://abstracts.isth.org/abstract/platelet-dysfunction-in-inherited-thrombocytopenias-with-predisposition-to-hematologic-malignancies-and-its-correlation-with-bleeding-analysis-of-23-patients-with-runx1-ankrd26-and-evt6-mutations/. Accessed September 24, 2023.
« Back to ISTH 2022 Congress
ISTH Congress Abstracts - https://abstracts.isth.org/abstract/platelet-dysfunction-in-inherited-thrombocytopenias-with-predisposition-to-hematologic-malignancies-and-its-correlation-with-bleeding-analysis-of-23-patients-with-runx1-ankrd26-and-evt6-mutations/