High-throughput microfluidic blood testing to phenotype genetically linked platelet disorders: an aid to diagnosis
Abstract: Linking the genetic background of patients with bleeding diathesis and altered platelet function remains challenging. We aimed to assess how a multiparameter microspot-based measurement of thrombus formation under flow can help identify patients with a platelet bleeding disorder. For this purpose, we studied 16 patients presenting with bleeding and/or albinism and suspected platelet dysfunction and 15 relatives. Genotyping of patients revealed a novel biallelic pathogenic variant in RASGRP2 (splice site c.240-1G>A), abrogating CalDAG-GEFI expression, compound heterozygosity (c.537del, c.571A>T) in P2RY12, affecting P2Y12 signaling, and heterozygous variants of unknown significance in the P2RY12 and HPS3 genes. Other patients were confirmed to have Hermansky-Pudlak syndrome type 1 or 3. In 5 patients, no genetic variant was found. Platelet functions were assessed via routine laboratory measurements. Blood samples from all subjects and day controls were screened for blood cell counts and microfluidic outcomes on 6 surfaces (48 parameters) in comparison with those of a reference cohort of healthy subjects. Differential analysis of the microfluidic data showed that the key parameters of thrombus formation were compromised in the 16 index patients. Principal component analysis revealed separate clusters of patients vs heterozygous family members and control subjects. Clusters were further segregated based on inclusion of hematologic values and laboratory measurements. Subject ranking indicated an overall impairment in thrombus formation in patients carrying a (likely) pathogenic variant of the genes but not in asymptomatic relatives. Taken together, our results indicate the advantages of testing for multiparametric thrombus formation in this patient population
- Standort
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Deutsche Nationalbibliothek Frankfurt am Main
- Umfang
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Online-Ressource
- Sprache
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Englisch
- Anmerkungen
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Blood advances. - 7, 20 (2023) , 6163-6177, ISSN: 2473-9537
- Ereignis
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Veröffentlichung
- (wo)
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Freiburg
- (wer)
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Universität
- (wann)
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2023
- Urheber
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Fernández, Delia Irene
Provenzale, Isabella
Canault, Matthias
Fels, Salome
Lenz, Antonia
Andresen, Felicia
Krümpel, Anne Katharina
Dupuis, Arnaud
Heemskerk, Johan W. M.
Böckelmann, Doris
Zieger, Barbara
- DOI
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10.1182/bloodadvances.2023009860
- URN
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urn:nbn:de:bsz:25-freidok-2377928
- Rechteinformation
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Open Access; Der Zugriff auf das Objekt ist unbeschränkt möglich.
- Letzte Aktualisierung
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25.03.2025, 13:47 MEZ
Datenpartner
Deutsche Nationalbibliothek. Bei Fragen zum Objekt wenden Sie sich bitte an den Datenpartner.
Beteiligte
- Fernández, Delia Irene
- Provenzale, Isabella
- Canault, Matthias
- Fels, Salome
- Lenz, Antonia
- Andresen, Felicia
- Krümpel, Anne Katharina
- Dupuis, Arnaud
- Heemskerk, Johan W. M.
- Böckelmann, Doris
- Zieger, Barbara
- Universität
Entstanden
- 2023
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