Thesis Yasmin de Wit

Summary

Platelets are the second most abundant blood cell type in the circulation and are key players in hemostasis and thrombosis. Activation of platelets by soluble ligands or subendothelial exposure of collagen, von Willebrand factor (vWF) or tissue factor (TF) results in upregulation of membrane-bound glycoproteins/integrins and granule release. Integrins or soluble glycoproteins from α-granules are essential for platelets to bind coagulation factors and agglutinate, but also to adhere to the vessel wall. Additionally, platelets secrete dense (δ) granules, which contain vasoconstrictors and reenforce platelet activation and aggregation.
To maintain hemostasis, platelets are involved in vascular repair, danger sensing and closely interact with endothelial cells and leukocytes. However, platelets can also detect and respond to local danger signs, such as infectious pathogens. Platelets use Toll-like receptors ( TLR) and adhesion receptors to mechanically probe the microenvironment. Recent studies demonstrate how platelets closely interact with neutrophils and the complement system during the innate immune response. Platelets express numerous complement components and receptors and a large spectrum of pro-inflammatory/modulatory chemokines and cytokines.
The scope of this thesis is to study markers of inflammation and immunothrombosis in patients suffering from COVID-19 and in the context of prophylactic and therapeutic administration of blood products with a special focus on both, the blood product itself and the recipient.