Intravascular hemolysis and the pathophysiology of sickle cell disease

Hemolysis is a fundamental feature of sickle cell anemia that contributes to its pathophysiology and phenotypic variability. Decompartmentalized hemoglobin, arginase 1, asymmetric dimethylarginine, and adenine nucleotides are all products of hemolysis that promote vasomotor dysfunction, proliferative vasculopathy, and a multitude of clinical complications of pulmonary and systemic vasculopathy, including pulmonary hypertension, leg ulcers, priapism, chronic kidney disease, and large-artery ischemic stroke. Nitric oxide (NO) is inactivated by cell-free hemoglobin in a dioxygenation reaction that also oxidizes hemoglobin to methemoglobin, a non-oxygen-binding form of hemoglobin that readily loses heme.…

• PO
  Patient-Centered Outcomes Research Institute
• UO
  University of Pittsburgh
• HC
  Hemophilia Center of Western Pennsylvania
• NI
  National Institutes of Health

  Awards: MD009162, 1R01HL125886-01, 1R01HL125886, 2P01HL103455, HL110849, HL098032