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. 2022 Nov 19;23(22):14386.
doi: 10.3390/ijms232214386.

Diagnosing Czech Patients with Inherited Platelet Disorders

Jan Louzil  1 , Jana Stikarova  2 , Dana Provaznikova  3 , Ingrid Hrachovinova  3 , Tereza Fenclova  3 , Jan Musil  4 , Martin Radek  5 , Jirina Kaufmanova  2   6 , Vera Geierova  1 , Eliska Ceznerova  2 , Peter Salaj  1 , Roman Kotlin  2
Affiliations

Diagnosing Czech Patients with Inherited Platelet Disorders

Jan Louzil et al. Int J Mol Sci. .

Abstract

A single-center study was conducted on 120 patients with inherited disorders of primary hemostasis followed at our hematological center. These patients presented a variety of bleeding symptoms; however, they had no definitive diagnosis. Establishing a diagnosis has consequences for the investigation of probands in families and for treatment management; therefore, we aimed to improve the diagnosis rate in these patients by implementing advanced diagnostic methods. According to the accepted international guidelines at the time of study, we investigated platelet morphology, platelet function assay, light-transmission aggregometry, and flow cytometry. Using only these methods, we were unable to make a definitive diagnosis for most of our patients. However, next-generation sequencing (NGS), which was applied in 31 patients, allowed us to establish definitive diagnoses in six cases (variants in ANKRD26, ITGA2B, and F8) and helped us to identify suspected variants (NBEAL2, F2, BLOC1S6, AP3D1, GP1BB, ANO6, CD36, and ITGB3) and new suspected variants (GFI1B, FGA, GP1BA, and ITGA2B) in 11 patients. The role of NGS in patients with suspicious bleeding symptoms is growing and it changes the diagnostic algorithm. The greatest disadvantage of NGS, aside from the cost, is the occurrence of gene variants of uncertain significance.

Keywords: ANKRD26; ITGA2B; NGS; clinical laboratory techniques; inherited platelet disorders; primary hemostasis.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Overview of the study. Abbreviations: ADP—adenosine diphosphate, epi—epinephrine, ara—arachidonic acid, GP—glycoprotein.
Figure 2
Figure 2
Representative pictures of dense granules (arrows in A–C) in platelets: (A) normal; (B) patient 10; (C) patient 11. Images were obtained using transmission electron microscopy (TEM; JEM-1010, JEOL, Peabody, MA, USA). Bar scale is 2 µm.
Figure 3
Figure 3
Summary of NGS results. Novel variants are in bold. All variants are heterozygous. For reference sequences and other information see Table 5.
See this image and copyright information in PMC

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