Proteomic profiling of hemostatic abnormalities

Hemostasis is a crucial and tightly regulated physiological process that controls the arrest of bleeding and the restoration of vascular integrity following damage. Dysregulation of hemostasis can result in hyper- or hypocoagulability, leading to clinical problems, including thrombosis and bleeding. Circulating proteins closely interact with the regulation of hemostasis and other biological processes, and differences in their abundance can be related to disease. In this thesis, we use protein profiling approaches to investigate the dysregulation of this process in patients at risk of thrombosis and bleeding. First, we studied plasma protein levels in patients before and during thromboembolic events. Although no shared biomarkers associated with thromboembolic events were identified, this approach captured changes in plasma protein levels resulting from anticoagulant treatment, as well as inflammatory responses related to the underlying disease. In patients with hematological malignancies, we used plasma profiling to unravel whether protein levels were related to the pathophysiology of bleeding. With this approach, we found that hemostatic proteins, as well as a large cluster of platelet proteins, were associated with bleeding severity at the time of sampling. Moreover, we highlighted the limited effect of platelet transfusions on plasma protein levels and further investigated the mechanisms underlying platelet activation. Finally, we explored protein profiling as an approach for research in preterm infants. We highlight that it can capture developmental changes and address the opportunities and challenges in neonatal research, thereby providing further support for fundamental and translational research. Show more