![]() The physiologic consequences of decreased NO bioavailability include chronic vasoconstriction, proliferative arteriopathy, and increased platelet aggregation and clotting, especially in the pulmonary vasculature. Arginase and methylarginine limit the activity of NO synthase to increase NO production to compensate for the destruction of NO. However, the severe chronic hemolysis in SCD saturates the haptoglobin system and depletes both haptoglobin and hemopexin. Multilayered adaptive mechanisms have evolved to clear hemoglobin and heme, including haptoglobin and hemopexin. This activates the innate immune system to produce inflammatory cytokines, promoting adhesion molecule expression on blood cells and endothelial cells. Both cell-free hemoglobin and free heme promote intense oxidative stress and serve as damage-associated molecular patterns (DAMPs). Cell-free hemoglobin scavenges NO in a rapid, nearly diffusion-limited dioxygenase reaction. ![]() Cell-free hemoglobin, free heme, arginase, and methylated arginines reduce nitric oxide (NO) bioavailability and promote oxidative stress and inflammation. The most harmful form of hemolysis is intravascular hemolysis, which releases the contents of red blood cells directly into plasma. Most of these responses are adaptive in the short term, but some of these can have maladaptive consequences in the long term. There are many pathophysiologic responses to the hemolysis and to its resulting anemia. Sickle cell anemia (SCA) is characterized by severe chronic hemolysis that gives rise to anemia. Mitigating the Effects of Hemolysis by Enhancing the Compensatory Response Mitigating the Effects of Hemolysis With Haptoglobin and Hemopexin Increasing cGMP by Inhibiting Its Hydrolysis via Phosphodiesterase 9ĭecreasing Hemolysis With Exchange Transfusionĭecreasing Hemolysis by Increasing Fetal Hemoglobinĭecreasing Hemolysis Through Induced Iron Deficiency ![]() Increasing cGMP by Inhibiting Its Hydrolysis via Phosphodiesterase 5 Increasing cGMP Production via Soluble Guanylyl Cyclase Agonists Historical Aspects of Hemolysis in Sickle Cell Diseaseĭense Red Cells and Irreversibly Sickled CellsĮxtravascular Versus Intravascular Hemolysisīiochemical Pathways Affected by Intravascular Hemolysis in SCD ![]()
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