Analysis of intravascular hemolysis markers in sickle cell disease patients

Abstract

Sickle Cell Anemia (SCA) is a disease caused by mutation in the beta²-globin gene. This mutation causes the formation of polymers with increased erythrocyte density, which is responsible for vaso-occlusive phenomena, characteristic of this disease. Eryptosis, which has recently been characterized, is a removal mechanism of abnormal or senescent erythrocytes that depends on exposure of the classic signs of phagocytosis, including decreased expression of CD47 in the erythrocyte membrane. The monocyte-macrophage system is responsible for the phagocytosis of senescent erythrocyte, the extravascular hemolysis, and it is stated that 2/3 of hemolysis of SCA occurs in this way. The rest of hemolysis occurs intravascularly, ie within the lumen leading to the release of free Hb in plasma. For its clearance is necessary the action of haptoglobin and hemopexin. Other mechanisms such as complement activation and increased susceptibility to lysis, are also described. The hydroxycarbamide (HU) is a potentially myelosuppressive drug, and multicenter studies have shown that it has direct effects on the pathophysiological mechanism of SCA leading to decreased vaso-occlusive phenomenon. Taking into account that hemolysis is a fundamental mechanism in the pathogenesis of SCA and that knowledge of its mechanisms has issues not fully explained, we aim to evaluate the importance of markers related to intravascular hemolysis and its relation to the steady state and vaso-occlusive crises in individuals with SCA, trying to evaluate in parallel the role of HU in this process. (AU)