Inherited Platelet Function Disorders: Algorithms for Phenotypic and Genetic Investigation

Paolo Gresele; Loredana Bury; Emanuela Falcinelli

doi:10.1055/s-0035-1570078

Seminars in Thrombosis and Hemostasis, Table of Contents

Semin Thromb Hemost 2016; 42(03): 292-305
DOI: 10.1055/s-0035-1570078

Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Inherited Platelet Function Disorders: Algorithms for Phenotypic and Genetic Investigation

Authors

Paolo Gresele

¹Division of Internal and Cardiovascular Medicine, Department of Medicine, University of Perugia, Perugia, Italy
Loredana Bury

¹Division of Internal and Cardiovascular Medicine, Department of Medicine, University of Perugia, Perugia, Italy
Emanuela Falcinelli

¹Division of Internal and Cardiovascular Medicine, Department of Medicine, University of Perugia, Perugia, Italy

Abstract

Inherited platelet function disorders (IPFDs) manifest with mucocutaneous bleeding and are frequently difficult to diagnose due to their heterogeneity, the complexity of the platelet activation pathways and a lack of standardization of the platelet function laboratory assays and of their use for this purpose. A rational diagnostic approach to IPFDs should follow an algorithm where clinical examination and a stepwise laboratory evaluation play a crucial role. A streamlined panel of laboratory tests, with consecutive steps of increasing level of complexity, allows the phenotypic characterization of most IPFDs. A first-line diagnosis of a significant fraction of the IPFD may be made also at nonspecialized centers by using relatively simple tests, including platelet count, peripheral blood smear, light transmission aggregometry, measurement of platelet granule content and release, and the expression of glycoproteins by flow cytometry. Some of the most complex, second- and third-step tests may be performed only in highly specialized laboratories. Genotyping, including the widespread application of next-generation sequencing, has enabled discovery in the last few years of several novel genes associated with platelet disorders and this method may eventually become a first-line diagnostic approach; however, a preliminary clinical and laboratory phenotypic characterization nowadays still remains crucial for diagnosis of IPFDs.

Keywords

bleeding - diagnostic algorithm - genetic testing - inherited platelet function disorders - laboratory investigation

Full Text

References

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