Novel Insights into the Pathophysiology and Treatment of Sickle Cell Disease

Real-world evidence of the burden of sickle cell disease: a 5-year longitudinal study at a Brazilian reference center

“…Blood transfusion remains a supportive therapy for many complications associated with SCD, including abrupt worsening of anemia, vasculopathy, VOCs and organ dysfunction. 2 , 7 , 8 The chronic pRBC transfusion regimen significantly reduces the risk of primary and secondary stroke in pediatric patients with SCD. 2 , 8 Nevertheless, chronic pRBC transfusion inevitably leads to secondary iron overload that can cause significant damage to many organs, such as the liver, endocrine system and heart.…”

“…Recurrent RBC sickling and hemolysis, combined with endovascular inflammation, result in acute and chronic organ damage at the cellular level, associated with acute, unpredictable and potentially life-threatening complications. 6 , 7 , 8 …”

“… 2 , 8 , 9 The HU is an inhibitor of the ribonucleotide reductase drug with many beneficial effects for treating people with SCD, including: increasing fetal Hb concentration in RBCs, improving nitric oxide metabolism and reducing red cell-endothelial interaction and erythrocyte density. 2 , 7 , 9 , 10 Such disease-modifying effects have been shown to decrease VOCs, acute chest syndrome (ACS), the number/length of hospitalizations and the need for transfusions, noticeably reducing the mortality rate and improving overall survival. 9 , 10 Blood transfusion currently represents a supportive therapy to manage anemia, vasculopathy and VOCs and to prevent serious complications, particularly the risk of primary and secondary stroke.…”

“… 1 , 2 , 9 The HSCT is a potentially curative procedure, although its use is restricted to a few patients due to the high cost, toxicity and limited availability of suitable donors. 1 , 7 In addition to HSCT, gene therapy is being explored as a curative option for SCD. The goal of gene therapy is to replace a patient's abnormal gene with new genetic material; it offers a potential cure for SCD without the need for a bone marrow donor or the toxicity associated with traditional conditioning regimens for HSCT.…”

“…The goal of gene therapy is to replace a patient's abnormal gene with new genetic material; it offers a potential cure for SCD without the need for a bone marrow donor or the toxicity associated with traditional conditioning regimens for HSCT. 7 …”