Platelet proteome reveals specific proteins associated with platelet activation and the hypercoagulable state in β-thalassmia/HbE patients.

Publisher: Nature Publishing Group Country of Publication: England NLM ID: 101563288 Publication Model: Electronic Cited Medium: Internet ISSN: 2045-2322 (Electronic) Linking ISSN: 20452322 NLM ISO Abbreviation: Sci Rep Subsets: MEDLINE

Original Publication: London : Nature Publishing Group, copyright 2011-

Platelet Activation*; Blood Platelets/*metabolism ; Hemoglobin E/*analysis ; beta-Thalassemia/*pathology; Adult ; Case-Control Studies ; Female ; Humans ; Male ; P-Selectin/blood ; P-Selectin/metabolism ; Peptide Fragments/blood ; Peptide Fragments/metabolism ; Proteomics ; Prothrombin/metabolism ; Young Adult ; beta-Thalassemia/blood

A hypercoagulable state leading to a high risk of a thrombotic event is one of the most common complications observed in β-thalassemia/HbE disease, particularly in patients who have undergone a splenectomy. However, the hypercoagulable state, as well as the molecular mechanism of this aspect of the pathogenesis of β-thalassemia/HbE, remains poorly understood. To address this issue, fifteen non-splenectomized β-thalassemia/HbE patients, 8 splenectomized β-thalassemia/HbE patients and 20 healthy volunteers were recruited to this study. Platelet activation and hypercoagulable parameters including levels of CD62P and prothrombin fragment 1 + 2 were analyzed by flow cytometry and ELISA, respectively. A proteomic analysis was conducted to compare the platelet proteome between patients and normal subjects, and the results were validated by western blot analysis. The β-thalassemia/HbE patients showed significantly higher levels of CD62P and prothrombin fragment 1 + 2 than normal subjects. The levels of platelet activation and hypercoagulation found in patients were strongly associated with splenectomy status. The platelet proteome analysis revealed 19 differential spots which were identified to be 19 platelet proteins, which included 10 cytoskeleton proteins, thrombin generation related proteins, and antioxidant enzymes. Our findings highlight markers of coagulation activation and molecular pathways known to be associated with the pathogenesis of platelet activation, the hypercoagulable state, and consequently with the thrombosis observed in β-thalassemia/HbE patients.

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0 (P-Selectin)
0 (Peptide Fragments)
0 (SELP protein, human)
0 (prothrombin fragment 1.2)
9001-26-7 (Prothrombin)
9034-61-1 (Hemoglobin E)

Date Created: 20190417 Date Completed: 20201015 Latest Revision: 20210109

20240829

PMC6465338

10.1038/s41598-019-42432-2

30988349