Sickle Cell Disease
Vincenzo Berghella in Maternal-Fetal Evidence Based Guidelines, 2022
Sickle cell disease describes a group of inherited disorders characterized by the presence of HbS. Sickle cell disease is associated with a mild to moderate chronic anemia. The term sickle cell disease includes sickle cell anemia (HbSS) (70% of cases), hemoglobin S combined with hemoglobin C (HbSC) (most of the remaining cases), hemoglobin S combined with β-thalassemia (HbSβ+ or HbSβ0), and other double heterozygous conditions causing sickling and thus, clinical disease (e.g., hereditary persistence of fetal hemoglobin (HgS/HPHP), and hemoglobin E (HbS/HbE) [7]. The clinical manifestations vary among these genotypes, with HbSβ0 usually with a similar severe phenotype as HbSS, HbSC associated with intermediate disease, and HbSβ+, HbSHPHP, and HbSE with mild or symptom-free disease [1, 5]. The term sickle cell anemia includes HbSS, and also HbSβ0 (due to its similar phenotype). The sickle cell trait is the heterozygous inheritance of HgbS and is characterized by benign clinical course without anemia, with protection against malaria [8].
Carrier Screening For Inherited Genetic Conditions
Vincenzo Berghella in Obstetric Evidence Based Guidelines, 2022
Sickle cell disease refers to a group of autosomal recessive disorders involving hemoglobin S. Hemoglobin S differs from hemoglobin A due to a single nucleotide substitution in the beta-globin gene on chromosome 11. The most severe form of sickle cell disease, sickle cell anemia, occurs in individuals with two copies of hemoglobin S. Sickle cell disorders can also occur in individuals who have hemoglobin S and another abnormality of B-globin structure or production such as hemoglobin C or beta-thalassemia. Sickle cell disease occurs most commonly in people of African origin. One in 12 African Americans has sickle cell trait. Patients with sickle cell disease are prone to distortion, or sickling, of their red blood cells under conditions of decreased oxygen tension. These distorted cells can result in increased viscosity, hemolysis, and anemia, resulting in interrupted blood supply to vital organs. These vasoocclusive crises can cause interruption of normal perfusion and function of several organs, including the spleen, lungs, kidney, heart, and brain. See Chap. 15 in Maternal-Fetal Medicine Evidence Based Guidelines.
Hemoglobin CC and SC Red Cells
Ronald L. Nagel in Genetically Abnormal Red Cells, 2019
Although the presence of homozygous hemoglobin C is often only moderately symptomatic, some aspects of hemoglobin SC disease approach the severity of sickle cell anemia. Both diseases are frequently diagnosed relatively late in life. However, while the major value in diagnosing hemoglobin C disease is prevention of inappropriate medical intervention, the diagnosis of SC disease is crucial to allow treatment of potentially severe complications such as retinopathy, femoral head necrosis, and possible complications during pregnancy.
HIV-1 infection in sickle cell disease and sickle cell trait: role of iron and innate response
Published in Expert Review of Hematology, 2022
Sickle cell disease (SCD) is an inherited hemoglobinopathy in which mutations in the β-globin gene (HBB) lead to the production of mutated hemoglobins of which the most prevalent are hemoglobin S (HbS, Glu6Val mutation) and hemoglobin C (Glu6Lys mutation) [1]. HbS polymerizes under low oxygen conditions leading to sickling of red blood cells (RBCs) and development of sickle cell anemia (SCA) that is characterized by hemolysis, vaso-occlusion and ischemia [2]. Clinical manifestations of SCA include recurrent pain crises and development of chronic organ damage caused by stroke, osteonecrosis, nephropathy, pulmonary disease and retinopathy [3]. SCA has also been associated with the increased risk of pulmonary hypertension, renal dysfunction, proteinuria, stroke and the overall increased mortality [4–9]. Other risk factors of SCA include left ventricular diastolic dysfunction, asplenia, cholestatic hepatic dysfunction and systemic iron overload [4,10]. SCD affects approximately 100,000 people in the U.S.A, primarily African Americans [11], and several million Africans, primarily in sub-Saharan Africa [2]. Worldwide, over 300,000 newborns in 2010 had SCD (75% in Sub-Saharan Africa) and by 2050 this number is expected to reach 400,000 [12].
Strategies to increase access to basic sickle cell disease care in low- and middle-income countries
Published in Expert Review of Hematology, 2022
Meghna Dua, Halima Bello-Manga, Yvonne M. Carroll, Aisha Amal Galadanci, Umma Abdulsalam Ibrahim, Allison A. King, Ayobami Olanrewaju, Jeremie H. Estepp
SCD is a monogenic red blood cell (RBC) disorder, where normal hemoglobin (HbA) is replaced by sickle hemoglobin (HbS). It is inherited as an autosomal codominant trait [1], and common types of SCD include homozygous hemoglobin SS disease, hemoglobin SC disease, and sickle beta-thalassemia[1]. It is a chronic and debilitating condition characterized by hemolytic anemia and endothelial dysfunction, with findings of vaso-occlusive crises, acute chest syndrome, increased risk of stroke, and cumulative multiorgan damage. Children with SCD are also at heightened risk of morbidity and mortality from specific infections due to functional asplenia. There are approximately 300,000–400,000 babies born with SCD globally, with over 75% of them born in Africa [1]. Nigeria, India, and the Democratic Republic of the Congo alone account for over 50% of patients with SCD [2]. This geographic distribution is attributed to the ‘malaria hypothesis’ that the HbS carrier state is protective against malaria infection, which was substantiated by the coexistence of high HbS carrier rates and malaria infections in Africa [3].
Emerging drugs for the treatment of sickle cell disease: a review of phase II/III trials
Published in Expert Opinion on Emerging Drugs, 2022
Jules M. Ross, Stéphanie Forté, Denis Soulières
Many trials have excluded hemoglobin SC disease from their studied population in the past, a subgroup of SCD representing 30% of sickle cell patients within the U.S. Usually considered a milder form and diagnosed at an older age, around 40% of patients experience pain episodes and some even have a similar phenotype to HbSS requiring chronic transfusions [95]. Until recently, only retrospective studies in HbSC had documented improvements in terms of acute pain events and hospitalizations [96]. An NHLBI evidence-based guideline has highlighted SC disease management as a critical knowledge gap, with a therapeutic approach largely inferred from studies of HbSS patients [96,97]. We believe individuals with HbSC disease should be enrolled in trials with newer agents, as their comorbidities remain largely similar to the HbSS population and they might benefit from the same agents. On this matter, the newer agents have been FDA-approved for HbSC genotype, even if it represented a minority of the studied population [94].
Related Knowledge Centers
- Anemia
- Glutamic Acid
- Lysine
- Plasmodium Falciparum
- Zygosity
- Hemoglobin
- Hemoglobin Subunit Beta
- Β-Globin Locus
- Sickle Cell Disease
- Genetic Resistance to Malaria