The Nlrp3 Inflammasome In Platelets Is Upregulated In Sickle Cell Disease And Promotes Platelet Aggregation And In Vitro Thrombosis

Sickle cell disease (SCD) is a severe monogenic disorder characterized by chronic hemolysis and abnormal coagulation and inflammation. Activated platelets play a critical role at the interphase of thrombosis and inflammation in the disease context. Sensing of free heme, a degradation byproduct of hemoglobin oxidation during hemolysis, involves the pattern recognition receptor nucleotide-binding domain leucine rich repeat containing protein 3 (NLRP3), which typically forms multiprotein inflammasome complexes and controls caspase-1 activity and cleavage of IL-1β not only in immune cells but also platelets. We have shown recently that the NLRP3 inflammasome in platelets controls platelet activation, aggregation, and in vitro thrombus formation, which was dependent on platelet bruton's tyrosine kinase (BTK). The role of the platelet NLRP3 inflammasome and BTK in SCD, however, is unexplored.