Abstract Number: PB1496
Meeting: ISTH 2020 Congress
Background: Inherited Platelet Disorders (IPD), a group of rare and heterogeneous diseases due to qualitative and/or quantitative platelet (PLT) defects, are increasingly recognized. Various strategies to IPD diagnosis were adopted but the best approach in still unknown.
Aims: Characterization of individuals with IPD followed in a Portuguese Center for Coagulopathies.
Methods: Probands from 94 unrelated families with PLT defects not explained by acquired causes, were evaluated by PLT morphometric and functional studies (lumiaggregometry and glycoprotein expression by flow cytometry); the study was oriented to Sanger sequencing (in presence of strong suspicion for a genetically homogeneous disease) and/or to Next-Generation-Sequencing (NGS). 93 affected and 40 unaffected family members (segregation studies) were also evaluated.
Results: Candidate variants in genes encoding for IPD were identified in 75 families (79.8%) (161 patients); 19 families (20.2%) had likely benign (6 families) or no candidate variants (13 families). Sanger sequencing confirmed the diagnosis in 91.7% of families with phenotypically identified IPD and NGS enabled the identification of candidate variants in 31 out of 48 families (64.6%). ITGA2B/ITGB3-RT (13 families, 17.3%), ANKRD26-RT (10.7%), ACTN1-RT (9.3%), MYH9-RD (9.3%), Glanzmann Thrombasthenia (8%), TUBB1-RT (6.7%), HPS (6.7%), bBSS (6.7%) and mBSS (5.3%) were the most prevalent IPD identified, representing 80% of the 75 families with molecular diagnosis being followed in our Centre.
Conclusions: The integration of clinical data with morphologic and functional tests, allowed a large number of phenotypically identified patients, including rare IPD such as ITGA2B/ITGB3-RT (investigated for a long time by systematic screen for αIIbβ3 deficiency in familial thrombocytopenia) with subsequent molecular identification of almost all the cases (>90%) by Sanger sequencing. The adopted strategy could justify a slightly different prevalence of various IPDs relative to other series and allowed the molecular identification in most (80%) of the families studied.
To cite this abstract in AMA style:Morais S, Lau C, Monteiro C, Pereira M, Gonçalves M, Gonçalves A, Oliveira J, Cruz E, Santos R, Lima M. Genetic Characterization of Inherited Platelet Disorders in a Single Portuguese Center for Coagulopathies [abstract]. Res Pract Thromb Haemost. 2020; 4 (Suppl 1). https://abstracts.isth.org/abstract/genetic-characterization-of-inherited-platelet-disorders-in-a-single-portuguese-center-for-coagulopathies/. Accessed October 2, 2023.
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