Figure 2.

Hemolysis-endothelial dysfunction. With intravascular hemolysis, erythrocytes release hemoglobin and arginase. Arginine is the precursor for NO production by the endothelium via NOS3. Arginase degrades L-arginine, the NOS3 substrate causing reduced NO production. Free plasma hemoglobin interacts with NO producing methemoglobin and nitrate depleting NO. These mechanisms occur during steady state and the amount of intravascular hemolysis varies among patients. An additional mechanism which occurs commonly during vasoocclusive episodes relates to free radicals production with the oxidation of NO. NO depletions will disturb the vasodilatorvasoconstrictor balance, ultimately leading to vasoconstriction of the blood vessels which will complicate the VOC further (A color version of this figure is available in the online journal)