Cerebrovascular disease is a leading cause of mortality worldwide, with numbers on the rise. It is a serious complication of a number of disease states, including sickle cell disease (SCD). Sickle cell disease (SCD) is a chronic, genetic disease resulting from a single amino acid substitution in the haemoglobin β chain of red blood cells, which affects millions of people worldwide. SCD patients suffer from a prothrombogenic phenotype with excess clot formation and thrombosis, leading to serious consequences such as ischemic stroke. Markers of neutrophil activity have revealed that circulating neutrophils of SCD patients are activated and as such this has provided indirect evidence for their implication in thrombosis. In the proposed studies we will investigate ways in which neutrophils contribute directly to cerebral thrombosis, something that is currently unknown and has never been investigated. We strongly believe that by understanding ways that neutrophils contribute not only to the systemic prothrombogenic phenotype of SCD, but more specifically to the actual local thrombus formation, we will uncover the potential implication of targeting neutrophils as a therapeutic strategy for this debilitating and life threatening disease.
Our findings will have far-reaching implications, as they will increase our knowledge of not only cerebral microvascular disease, but also microvascular thrombosis in general and the role that neutrophils play in linking inflammation and thrombosis in SCD.