Pathogenic Aspects of Inherited Platelet Disorders

Boeckelmann, Doris; Glonnegger, Hannah; Sandrock-Lang, Kirstin; Zieger, Barbara

doi:10.1055/a-1665-6249

Cited by 5 publications

(3 citation statements)

References 102 publications

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“…If these genes are not only involved in platelet formation or function, but are also essential for other organ systems, the platelet disorder may also be a component of complex syndromic diseases. [1][2][3][4] In addition, some genetic defects result in relatively mild and clinically benign thrombocytopenia, but predispose to malignancies and may be considered as cancer predisposition syndromes. 5 The exact prevalence of IPD is widely unknown.…”

Section: Inherited Platelet Disordersmentioning

confidence: 99%

THROMKIDplus Patient Registry and Biomaterial Banking for Children with Inherited Platelet Disorders

Ballmaier,

Germeshausen,

Schulze

et al. 2023

Hamostaseologie

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Inherited platelet disorders (IPDs) represent a heterogeneous group of disorders that include both quantitative (thrombocytopenia or thrombocytosis) and qualitative (thrombocytopathy) defects. To gain better knowledge about the prevalence, pathogenesis, and clinical consequences of specific diseases, to improve diagnosis and treatment of patients with IPD, and to support translational research on a genetic, molecular, and physiological basis, the THROMKIDplus study group currently comprising 24 sites in Germany, Austria, and Switzerland decided to establish a patient registry with associated biomaterial banking for children. This registry is designed as a retrospective-prospective, multicenter observational study and supposed to launch in the second half of 2023. Blood smears, plasma, platelet pellets, and DNA of patients will be stored in certified biomaterial banks for future translational research projects. The main inclusion criteria are (1) diagnosis of or highly suspected IPD after assessment of a THROMKIDplus competence center and (2) patients aged 0 to 17 years. Initial and follow-up data on patient history, laboratory parameters, standardized documentation of bleeding tendency, and congenital defects are collected according to good clinical practice and current data protection acts by using the MARVIN platform, a broadly used data management system supported by the German Society for Pediatric Oncology Hematology (GPOH). The THROMKIDplus study group intends to enroll ∼200 patients retrospectively and an annual amount of ∼50 patients prospectively.

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Section: Inherited Platelet Disordersmentioning

confidence: 99%

THROMKIDplus Patient Registry and Biomaterial Banking for Children with Inherited Platelet Disorders

Ballmaier,

Germeshausen,

Schulze

et al. 2023

Hamostaseologie

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show abstract

“…The study of platelet dysfunction is inherently complex due to the heterogeneity of the underlying pathophysiology. 127 Therefore, no single method has yet been identified as the definitive and universally simple diagnostic for platelet dysfunctions. While LTA has established itself as gold standard due to its ability to detect a wide range of inherited, acquired, and drug-induced platelet defects, it is not without limitations and concerns, many of which are currently being addressed through technical improvements and implementations.…”

Section: Molecular Genetics and New Scientific Approachesmentioning

confidence: 99%

Classic Light Transmission Platelet Aggregometry: Do We Still Need it?

Gebetsberger,

Prüller

2023

Hamostaseologie

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For more than 50 years, light transmission aggregometry has been accepted as the gold standard test for diagnosing inherited platelet disorders in platelet-rich plasma, although there are other functional approaches performed in whole blood. In this article, several advantages and disadvantages of this technique over other laboratory approaches are discussed in the view of recent guidelines, and the necessity of functional assays, such as light transmission aggregometry in the era of molecular genetic testing, is highlighted.

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“…Moreover, ITs are often unrecognized and misdiagnosed with most common forms of thrombocytopenia. In addition, in more than of 50% of patients with ITs, the molecular cause remains unknown ( 7 , 8 ).…”

Section: Introductionmentioning

confidence: 99%

“CHildren with Inherited Platelet disorders Surveillance” (CHIPS) retrospective and prospective observational cohort study by Italian Association of Pediatric Hematology and Oncology (AIEOP)

et al. 2022

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BackgroundInherited thrombocytopenias (ITs) are rare congenital bleeding disorders characterized by different clinical expression and variable prognosis. ITs are poorly known by clinicians and often misdiagnosed with most common forms of thrombocytopenia.Material and methods“CHildren with Inherited Platelet disorders Surveillance” study (CHIPS) is a retrospective – prospective observational cohort study conducted between January 2003 and January 2022 in 17 centers affiliated to the Italian Association of Pediatric Hematology and Oncology (AIEOP). The primary objective of this study was to collect clinical and laboratory data on Italian pediatric patients with inherited thrombocytopenias. Secondary objectives were to calculate prevalence of ITs in Italian pediatric population and to assess frequency and genotype–phenotype correlation of different types of mutations in our study cohort.ResultsA total of 139 children, with ITs (82 male - 57 female) were enrolled. ITs prevalence in Italy ranged from 0.7 per 100,000 children during 2010 to 2 per 100,000 children during 2022. The median time between the onset of thrombocytopenia and the diagnosis of ITs was 1 years (range 0 - 18 years). A family history of thrombocytopenia has been reported in 90 patients (65%). Among 139 children with ITs, in 73 (53%) children almost one defective gene has been identified. In 61 patients a pathogenic mutation has been identified. Among them, 2 patients also carry a variant of uncertain significance (VUS), and 4 others harbour 2 VUS variants. VUS variants were identified in further 8 patients (6%), 4 of which carry more than one variant VUS. Three patients (2%) had a likely pathogenic variant while in 1 patient (1%) a variant was identified that was initially given an uncertain significance but was later classified as benign. In addition, in 17 patients the genetic diagnosis is not available, but their family history and clinical/laboratory features strongly suggest the presence of a specific genetic cause. In 49 children (35%) no genetic defect were identified. In ninetyseven patients (70%), thrombocytopenia was not associated with other clinically apparent disorders. However, 42 children (30%) had one or more additional clinical alterations.ConclusionOur study provides a descriptive collection of ITs in the pediatric Italian population.

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Pathogenic Aspects of Inherited Platelet Disorders

Cited by 5 publications

References 102 publications

THROMKIDplus Patient Registry and Biomaterial Banking for Children with Inherited Platelet Disorders

THROMKIDplus Patient Registry and Biomaterial Banking for Children with Inherited Platelet Disorders

Classic Light Transmission Platelet Aggregometry: Do We Still Need it?

“CHildren with Inherited Platelet disorders Surveillance” (CHIPS) retrospective and prospective observational cohort study by Italian Association of Pediatric Hematology and Oncology (AIEOP)

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