Abstract Number: OC 21.1
Meeting: ISTH 2021 Congress
Theme: Platelet Disorders, von Willebrand Disease and Thrombotic Microangiopathies » Inherited Thrombocytopenias
Background: Inherited platelet disorders (IPDs) are characterized by reduced or dysfunctional platelets. Diagnostic tools include clinical evaluation, functional tests and genetic analysis. We established a diagnostic method on the blood smear by immunofluorescence microscopy.
Aims: To compare the outcomes of immunofluorescence with those of genetic testing in a cohort of patients with suspected IPD.
Methods: Four Institutes from Greifswald, Germany, Murcia, Spain, Copenhagen, Denmark, and Malmö, Sweden, participated in the study. Subjects were enrolled from January 2019 to December 2020 by Centers of Murcia, Copenhagen and Malmö, to whom they were referred for genetic investigation. Blood smears were centralized in Greifswald and blindly analyzed. Morphologic changes were reported and potential diagnoses formulated. Subsequently, genetic results were unblinded and the comparison performed. Patients or their legal guardians signed written informed consent.
Results: 94 subjects of 70 pedigrees were enrolled. Microscopic analysis identified alterations suggestive for a specific IPD in 50 cases (53%). In 39 (42%) abnormalities not typical for known IPDs were reported and in 5 (5%) no alterations were found.
Genetic testing diagnosed a specific IPD in 42 pedigrees (60%). In total, 20 different IPDs were identified. Among these, 11 were identified by immunofluorescence based on known specific phenotypic changes. In 3 forms we identified previously unknown phenotypes, while in 6 immunofluorescence did not allow a specific diagnosis. (Table)
In 19 pedigrees (27%) variants of unknown significance (VUS) were found. Among them, in 7 (37%) immunofluorescence found phenotypic changes typical for pathogenic variants. In 9 pedigrees (13%) no variants were found. Among them, in 8 (89%) immunofluorescence found phenotypic changes in platelet structures (e.g. cytoskeleton or granules). 
Outcome of immunofluorescence (IF) assessment on the blood smear in the 42 pedigrees who received a defined molecular diagnosis of inherited platelet disorder (IPD). #based on previously reported diagnostic patterns; *previously unreported diagnostic patterns.
Conclusions: Immunofluorescence on the blood smear is an effective diagnostic tool for a substantial group of IPDs. It can help VUS interpretation and provide clinicians with information about changes in platelet structures that may account for bleeding phenotype.
To cite this abstract in AMA style:
Zaninetti C, Rivera J, Leinøe E, Zetterberg E, Bastida JM, Rossing M, Wolff M, Freyer C, Greinacher A. Diagnosing Inherited Platelet Disorders: Immunofluorescence on the Blood Smear in Comparison with Genetic Testing [abstract]. Res Pract Thromb Haemost. 2021; 5 (Suppl 2). https://abstracts.isth.org/abstract/diagnosing-inherited-platelet-disorders-immunofluorescence-on-the-blood-smear-in-comparison-with-genetic-testing/. Accessed August 15, 2022.« Back to ISTH 2021 Congress
ISTH Congress Abstracts - https://abstracts.isth.org/abstract/diagnosing-inherited-platelet-disorders-immunofluorescence-on-the-blood-smear-in-comparison-with-genetic-testing/