Hemorheology, pathophysiology, and current treatment of sickle cell disease: A minireview

Abstract

Sickle cell disease (SCD) is an inherited autosomal recessive hemoglobinopathy. This red cell disorder is a molecular disease caused by a point mutation of the gene encoding β-globin yielding characteristic sickle Hb (HbS; βGlu6Val). HbS makes red cells rigid and fragile. Red cells show a sickle shape by HbS polymerization in deoxygenated state, which severely impairs cellular deformability. Systemic vaso-occlusive crisis (VOC) is the main characteristics observed in patients with SCD, and persistent ischemia-reperfusion injury impairs vascular redox balance leading to platelet activation, leukocyte adhesion, and endothelial dysfunction. Sickle cells with short lifespans are easily hemolyzed, which induces anemia (sickle cell anemia), releases HbS into circulation, and reduces bioavailability of nitric oxide underlying systemic vascular inflammation. Such rheological derangement and vascular aging are heterogeneous among the patients with SCD. Hydroxyurea is a drug approved first and used widely to ameliorate SCD symptoms. Several drugs have emerged recently as promising disease-modifying agents leading to restoration of hemorheology and reduction in hemolysis and painful VOC. This review article focuses on the hemorheology, pathophysiology, and recent advances in the disease-modifying treatments and healthcare of SCD patients to alert that rapid globalization may place Japan out of the exception for SCD-endemic countries.