Abstract Number: PB1493
Meeting: ISTH 2020 Congress
Theme: Platelet Disorders and von Willebrand Disease » Platelet Function Disorders, Hereditary
Background: Glanzmann’s thrombasthenia (GT) is a rare autosomal recessive disease which occurs more frequently in populations in which consanguineous marriages is practiced. GT is characterized by a quantitative or qualitative defect of the platelet αIIbβ3 (GPIIb/IIIa) receptor caused by pathogenic variants of the ITGA2B and ITGB3 genes, respectively. Patients present with a moderate to severe bleeding tendency, having normal platelet count, morphology and normal first line coagulation tests. The disease is diagnosed and classified by platelet aggregometry and by flow cytometry. Molecular genetic analyses confirm the diagnosis and help to understand the pathomechanism.
Aims: Aim of the study was to identify the biochemical and molecular genetic defects in patients with Glanzmann thrombasthenia in Pakistan.
Methods: The data of the patients were collected from NIBD Karachi, Fatimid foundation Karachi and Chughtai’s Lab, Lahore. Patients diagnosed with platelet functional defects were identified. CBC (complete blood count) was done to identify platelet morphology and counts. Prothrombin time (PT), Activated partial thromboplastin time (APTT), Fibrinogen levels and platelet aggregation studies were performed. Further investigations were initiated using flow cytometric analysis (platelet CD41 and CD42 glycoprotein expression). In addition, molecular genetic analyses were performed using Sanger sequencing method.
Results: In 20 out of the 26 patients suffering from platelet functional defects in our cohort GT was diagnosed or suspected: 12 (46.1%) males and 8 (30.7%) female patients. Pathogenic or likely pathogenic variants in the candidate genes ITGA2B and ITGB3 were identified in 15 patients. History of consanguinity was found in 88.4% of the patients. Eight novel pathogenic/likely pathogenic variants were identified. Family genotyping was performed in 2 families.
Conclusions: GT is commonest platelet disorder identified among inherited platelet disorders. Variant analyses reveal missense mutations were the most frequent. Flowcytometric analyses reveals GT type 1 as the most common disorder found in this cohort.
To cite this abstract in AMA style:
Siddiqi MYJ, Boeckelmann D, Naz A, Ahmed S, Najmuddin A, Imran A, Zieger B, Shamsi TS. Glanzmann Thrombasthenia in Pakistani Patients: Biochemical Analyses & Identification of Novel Pathogenic Variants in the Fibrinogen Receptor αIIbβ3 [abstract]. Res Pract Thromb Haemost. 2020; 4 (Suppl 1). https://abstracts.isth.org/abstract/glanzmann-thrombasthenia-in-pakistani-patients-biochemical-analyses-identification-of-novel-pathogenic-variants-in-the-fibrinogen-receptor-%ce%b1iib%ce%b23/. Accessed April 19, 2024.« Back to ISTH 2020 Congress
ISTH Congress Abstracts - https://abstracts.isth.org/abstract/glanzmann-thrombasthenia-in-pakistani-patients-biochemical-analyses-identification-of-novel-pathogenic-variants-in-the-fibrinogen-receptor-%ce%b1iib%ce%b23/