The invisible string of coagulation, complement, iron, and inflammation in sickle cell disease.

Several studies implicate dysregulation of the ADAMTS-13/VWF axis as playing a major role in vaso-occlusive events (VOE) in SCD. Another highlight is reducing iron overload, which has beneficial effects on erythrocyte and neutrophil function that reduce VOE and inflammation. Multiple studies suggest that targeting HO-1/ROS in erythrocytes, platelets, and endothelium can attenuate disease pathology. New insights into coagulation activation identify intrinsic coagulation factor XII as a central regulator of many thromboinflammatory pathologies in SCD. The complement cascade and modulators of neutrophil function and release of neutrophil extracellular traps are also discussed.