Diagnosis of Inherited Platelet Disorders on a Blood Smear

Zaninetti, Carlo; Greinacher, Andreas

doi:10.3390/jcm9020539

Cited by 30 publications

(35 citation statements)

References 106 publications

(133 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…A diagnostic algorithm for inherited thrombocytopenias was proposed several years ago and it is still valid to orient towards specific disorders [ 66 , 67 ]. History and clinical examination are crucial for patients with syndromic forms, whereas cell counting and the examination of peripheral blood films may guide diagnosis in non-syndromic forms [ 68 ]. However, in most cases genetic studies are required to confirm the diagnostic suspicion [ 3 , 69 ].…”

Section: Diagnostic Approachmentioning

confidence: 99%

Learning the Ropes of Platelet Count Regulation: Inherited Thrombocytopenias

Bury¹,

Falcinelli²,

Gresele³

2021

JCM

View full text Add to dashboard Cite

Inherited thrombocytopenias (IT) are a group of hereditary disorders characterized by a reduced platelet count sometimes associated with abnormal platelet function, which can lead to bleeding but also to syndromic manifestations and predispositions to other disorders. Currently at least 41 disorders caused by mutations in 42 different genes have been described. The pathogenic mechanisms of many forms of IT have been identified as well as the gene variants implicated in megakaryocyte maturation or platelet formation and clearance, while for several of them the pathogenic mechanism is still unknown. A range of therapeutic approaches are now available to improve survival and quality of life of patients with IT; it is thus important to recognize an IT and establish a precise diagnosis. ITs may be difficult to diagnose and an initial accurate clinical evaluation is mandatory. A combination of clinical and traditional laboratory approaches together with advanced sequencing techniques provide the highest rate of diagnostic success. Despite advancement in the diagnosis of IT, around 50% of patients still do not receive a diagnosis, therefore further research in the field of ITs is warranted to further improve patient care.

show abstract

Section: Diagnostic Approachmentioning

confidence: 99%

Learning the Ropes of Platelet Count Regulation: Inherited Thrombocytopenias

Bury¹,

Falcinelli²,

Gresele³

2021

JCM

View full text Add to dashboard Cite

show abstract

“…The range is so wide due to the varied levels of phenotypic severity. The presence of these inclusions help distinguish MYH9 anomalies from other hematologic abnormalities with high specificity and sensitivity [35].…”

Section: Macrothrombocytopeniamentioning

confidence: 99%

Linking the Landscape of MYH9-Related Diseases to the Molecular Mechanisms that Control Non-Muscle Myosin II-A Function in Cells

Asensio-Juárez

Llorente-González

Vicente‐Manzanares

2020

Cells

View full text Add to dashboard Cite

The MYH9 gene encodes the heavy chain (MHCII) of non-muscle myosin II A (NMII-A). This is an actin-binding molecular motor essential for development that participates in many crucial cellular processes such as adhesion, cell migration, cytokinesis and polarization, maintenance of cell shape and signal transduction. Several types of mutations in the MYH9 gene cause an array of autosomal dominant disorders, globally known as MYH9-related diseases (MYH9-RD). These include May-Hegglin anomaly (MHA), Epstein syndrome (EPS), Fechtner syndrome (FTS) and Sebastian platelet syndrome (SPS). Although caused by different MYH9 mutations, all patients present macrothrombocytopenia, but may later display other pathologies, including loss of hearing, renal failure and presenile cataracts. The correlation between the molecular and cellular effects of the different mutations and clinical presentation are beginning to be established. In this review, we correlate the defects that MYH9 mutations cause at a molecular and cellular level (for example, deficient filament formation, altered ATPase activity or actin-binding) with the clinical presentation of the syndromes in human patients. We address why these syndromes are tissue restricted, and the existence of possible compensatory mechanisms, including residual activity of mutant NMII-A and/or the formation of heteropolymers or co-polymers with other NMII isoforms.

show abstract

“…Lamp 1, Lamp 2, and CD63 labeling can help to identify δ-SPD on a smear [86,87]. Using high resolution microscopy, a two-color image method has been proposed by Westmorland et al [88], which employs sequential image acquisition during excitation of the sample with laser light at 488 nm for CD63 and 561 nm for tubulin in order to delimit the exact individual platelet areas.…”

Section: Proteins Of Dense-granulesmentioning

confidence: 99%

Platelet δ-Storage Pool Disease: An Update

Dupuis

Bordet

Eckly

et al. 2020

JCM

View full text Add to dashboard Cite

Platelet dense-granules are small organelles specific to the platelet lineage that contain small molecules (calcium, adenyl nucleotides, serotonin) and are essential for the activation of blood platelets prior to their aggregation in the event of a vascular injury. Delta-storage pool diseases (δ-SPDs) are platelet pathologies leading to hemorrhagic syndromes of variable severity and related to a qualitative (content) or quantitative (numerical) deficiency in dense-granules. These pathologies appear in a syndromic or non-syndromic form. The syndromic forms (Chediak–Higashi disease, Hermansky–Pudlak syndromes), whose causative genes are known, associate immune deficiencies and/or oculocutaneous albinism with a platelet function disorder (PFD). The non-syndromic forms correspond to an isolated PFD, but the genes responsible for the pathology are not yet known. The diagnosis of these pathologies is complex and poorly standardized. It is based on orientation tests performed by light transmission aggregometry or flow cytometry, which are supplemented by complementary tests based on the quantification of platelet dense-granules by electron microscopy using the whole platelet mount technique and the direct determination of granule contents (ADP/ATP and serotonin). The objective of this review is to present the state of our knowledge concerning platelet dense-granules and the tools available for the diagnosis of different forms of δ-SPD.

show abstract

Diagnosis of Inherited Platelet Disorders on a Blood Smear

Cited by 30 publications

References 106 publications

Learning the Ropes of Platelet Count Regulation: Inherited Thrombocytopenias

Learning the Ropes of Platelet Count Regulation: Inherited Thrombocytopenias

Linking the Landscape of MYH9-Related Diseases to the Molecular Mechanisms that Control Non-Muscle Myosin II-A Function in Cells

Platelet δ-Storage Pool Disease: An Update

Contact Info

Product

Resources

About