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Sickle Cell Disease
Published in Vincenzo Berghella, Maternal-Fetal Evidence Based Guidelines, 2022
Sickle cell disease has an autosomal recessive inheritance pattern. Concordant with an autosomal recessive pattern of inheritance, if both parents carry one HbS gene, the fetus has a 25% chance of having sickle cell disease, 50% chance of having sickle cell trait, and 25% chance of being unaffected [5]. As noted earlier, other forms of sickle cell disease result from co-inheritance of HbS with other abnormal β-globin chain variants, the most common forms being sickle hemoglobin C disease (HbSC) and two types of sickle β-thalassemia (HbSβ+ thalassemia and HbSβ0 thalassemia). Inheriting one HbS gene results in sickle cell trait, while inheriting two HbS genes results in sickle cell disease.
Host Defense II: Acquired Immunity
Published in Constantin A. Bona, Francisco A. Bonilla, Textbook of Immunology, 2019
Constantin A. Bona, Francisco A. Bonilla
In red blood cells of patients with sickle cell trait, parasites induce sickling. The sickled cells are rapidly cleared from the circulation in the spleen, aborting the parasite life cycle. Sickling may also kill the parasites directly. In hemoglobin C disease, cells are very resistant to lysis and the merozoites cannot escape to propagate the infection. Hemoglobin E (possibly the most common mutant human hemoglobin) leads to erythrocyte resistance for replication and rapid clearance of infected cells. In hereditary persistence of fetal hemoglobin the fetal hemoglobin retards growth of Plasmodia. Ovalocytes (erythrocytes with altered membrane structure occurring in individuals with hereditary ovalocytosis) are resistant to penetration by P. falciparum. In glucose-6-phosphate dehydrogenase deficiency erythrocytes are resistant to plasmodium replication, possibly because the parasite requires the host enzyme. Epidemiologic and population studies strongly suggest a protective effect of various thallassemias in malaria, but the mechanism is not known.
Anemia: Approach to Diagnosis
Published in Harold R. Schumacher, William A. Rock, Sanford A. Stass, Handbook of Hematologic Pathology, 2019
Sickle cell and other hemoglobinopathies result in extravascular hemolysis and accompanying elevations of serum lactate dehydrogenase and total and unconjugated bilirubin. Hemoglobin crystals and target cells in hemoglobin C disease and the sickle cells of sickle cell SS disease are typical abnormalities of anisocytosis. Heterozygous sickle cell disease may be identified by a sickle cell prep, and hemoglobin electrophoresis will help to identify other abnormal hemoglobins. Anemias combining the disorders of sickle cell disease, iron deficiency, thalassemia, hemoglobin C disease, and red cell enzymophathies present challenging diagnostic problems requiring additional laboratory testing including free erythrocyte protoporphyrin, transferrin saturation, hemoglobin electrophoresis, enzymatic, and genetic studies. When other causes of hemolysis are excluded and there is no evidence of abnormal hemoglobin, a red cell enzymopathy should be considered. Congenital or acquired defects may be found, as in patients with pyruvate-kinase deficiency, which may be associated with the development of preleukemia.
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].
Phenotypic variation in sickle cell disease: the role of beta globin haplotype, alpha thalassemia, and fetal hemoglobin in HbSS
Published in Expert Review of Hematology, 2022
Sickle cell disease covers a variety of conditions in which pathology results from the inheritance of sickle hemoglobin (HbS) [2]. The more common genotypes at birth, in populations of West African ancestry, include homozygous sickle cell disease (HbSS), sickle cell-hemoglobin C disease (HbSC), sickle cell-beta+ thalassemia (Sβ+ thal.) and sickle cell-betao thalassemia (Sβo thal.). Less common genotypes include sickle cell-HbD Punjab, sickle cell-HbO Arab, and sickle cell-HbLepore. Excluded from this definition is the sickle cell trait (HbAS) in which 20–45% HbS is not sufficient under normal conditions to cause serious pathology, although under unusual condition of environmental hypoxia, cyanotic congenital heart disease or respiratory depression, symptoms may occur [3]. Also excluded is the condition, sickle cell-hereditary persistence of fetal hemoglobin (HbS/HPFH) in which the inheritance of an HPFH gene from one parent is associated with 20–30% HbF distributed evenly throughout the red cell population, which inhibits intravascular sickling and is asymptomatic [4].