The proteomic landscape of platelets in Glanzmann thrombasthenia

Background: Glanzmann thrombasthenia (GT) is a rare, inherited platelet function disorder caused by mutations in the integrins of the fibrinogen receptor αIIbβ3. The deficiency can be quantitative (type I/II) or qualitative (type III). This causes lack of platelet aggregation and consequently these patients suffer from a moderate to severe bleeding tendency. Besides the absence or functional alteration of the integrins αIIb and β3, little is known about the proteomic landscape of platelets from people with GT. Objectives: We aim to evaluate the proteomic landscape of platelets in GT. Patient/Methods: Thirteen patients with GT from the Thrombocytopathy in the Netherlands (TiN) study and healthy controls were included in this study. Whole blood flow cytometry analysis was performed to quantify αIIbβ3 expression. GT was genetically confirmed. Platelets were isolated and prepared for liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS). Results: Flow cytometry and LC-MS/MS based αIIb expression correlated well and resulted in 11 type I GT and 2 type III GT patients. Analysis of the LC-MS/MS data revealed similar platelet proteome in GT vs healthy platelets, with downregulation of a few platelet specific proteins that are associated with α-granules. Upregulated proteins in GT were almost all genuine plasma proteins rather than platelet specific proteins. Conclusions: The proteomic landscape of GT platelets is overall similar as in healthy platelets, with downregulation of some platelet specific α-granule proteins.