Repository logo
 

Advances in understanding the pathogenesis of hereditary macrothrombocytopenia.

Published version
Peer-reviewed

Change log

Authors

Megy, Karyn 
Vuckovic, Dragana 

Abstract

Low platelet count, or thrombocytopenia, is a common haematological abnormality, with a wide differential diagnosis, which may represent a clinically significant underlying pathology. Macrothrombocytopenia, the presence of large platelets in combination with thrombocytopenia, can be acquired or hereditary and indicative of a complex disorder. In this review, we discuss the interpretation of platelet count and volume measured by automated haematology analysers and highlight some important technical considerations relevant to the analysis of blood samples with macrothrombocytopenia. We review how large cohorts, such as the UK Biobank and INTERVAL studies, have enabled an accurate description of the distribution and co-variation of platelet parameters in adult populations. We discuss how genome-wide association studies have identified hundreds of genetic associations with platelet count and mean platelet volume, which in aggregate can explain large fractions of phenotypic variance, consistent with a complex genetic architecture and polygenic inheritance. Finally, we describe the large genetic diagnostic and discovery programmes, which, simultaneously to genome-wide association studies, have expanded the repertoire of genes and variants associated with extreme platelet phenotypes. These have advanced our understanding of the pathogenesis of hereditary macrothrombocytopenia and support a future clinical diagnostic strategy that utilises genotype alongside clinical and laboratory phenotype data.

Description

Funder: Bristol NIHR Biomedical Research Centre; Id: http://dx.doi.org/10.13039/100015250

Keywords

genomics, macrothrombocytopenia, megakaryopoiesis, platelets, polygenic, Adolescent, Adult, Aged, Blood Platelets, Cell Size, Cohort Studies, Female, Genetic Heterogeneity, Genome-Wide Association Study, Humans, Male, Mean Platelet Volume, Middle Aged, Multifactorial Inheritance, Phenotype, Platelet Count, Thrombocytopenia, Transcription Factors, Young Adult

Journal Title

Br J Haematol

Conference Name

Journal ISSN

0007-1048
1365-2141

Volume Title

195

Publisher

Wiley
Sponsorship
Medical Research Council (MR/P02002X/1)