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Query: UMLS:C0002895 (sickle cell disease)
 11,747 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Sickle cell anemia, a congenital hemolytic type of anemia due to a genetic defect in the beta chain of the globin molecule can cause severe disease. During pregnancy, the risk for preeclampsia and deep venous thrombosis is increased in patients with sickle cell anemia. Occlusion of placenta blood vessels with rigid deformed erythrocytes can cause repeated miscarriages and intra-uterine fetal death. Repeated blood transfusions can prevent these complications by reducing the concentration of abnormal hemoglobin S. We report on the evolution of five pregnancies in three patients with sickle cell anemia who received multiple blood transfusions during gestation, and discuss advantages and risks involved in the care of such cases.
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PMID:[Sickle cell anemia and pregnancy: considerations on systematic prophylactic transfusion]. 1131 68

Hydroxyurea is a drug that is used to treat some patients with sickle cell disease. We have measured the deformability of sickle erythrocytes incubated in hydroxyurea in vitro and found that hydroxyurea acts to decrease the deformability of these cells. The deformability of normal erythrocytes was not significantly affected by hydroxyurea except at very high concentrations. Hydroxyurea also did not consistently reduce the deformability of sickle erythrocyte ghosts. We propose that the decreased deformability, observed in vitro, is due to the formation of methemoglobin and other oxidative processes resulting from the reaction of hydroxyurea and oxyhemoglobin. Although the reaction with normal hemoglobin is similar to that of sickle hemoglobin, the sickle erythrocytes are affected more. We propose that the sickle erythrocyte membrane is more susceptible to the reaction products of the reaction of hemoglobin and hydroxyurea. An earlier report has shown that hydroxyurea increases the deformability of erythrocytes in patients on hydroxyurea. Taken together, these data suggest that the improved rheological properties of sickle erythrocytes in vivo are due to the elevated numbers of F cells [cells with fetal hemoglobin]. The presence of the nitrosyl hemoglobin or methemoglobin from the reaction with hydroxyurea may also benefit patients in vivo by reducing sickling.
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PMID:In vitro exposure to hydroxyurea reduces sickle red blood cell deformability. 1139 10

Sickle cell anemia (SCA) is a disease caused by production of abnormal hemoglobin, which binds with other abnormal hemoglobin molecules within the red blood cell to cause rigid deformation of the cell. This deformation impairs the ability of the cell to pass through small vascular channels; sludging and congestion of vascular beds may result, followed by tissue ischemia and infarction. Infarction is common throughout the body in the patient with SCA, and it is responsible for the earliest clinical manifestation, the acute pain crisis, which is thought to result from marrow infarction. Over time, such insults result in medullary bone infarcts and epiphyseal osteonecrosis. In the brain, white matter and gray matter infarcts are seen, causing cognitive impairment and functional neurologic deficits. The lungs are also commonly affected, with infarcts, emboli (from marrow infarcts and fat necrosis), and a markedly increased propensity for pneumonia. The liver, spleen, and kidney may experience infarction as well. An unusual but life-threatening complication of SCA is sequestration syndrome, wherein a considerable amount of the intravascular volume is sequestered in an organ (usually the spleen), causing vascular collapse; its pathogenesis is unknown. Finally, because the red blood cells are abnormal, they are removed from the circulation, resulting in a hemolytic anemia. For the patient with SCA, however, the ischemic complications of the disease far outweigh the anemia in clinical importance.
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PMID:Sickle cell anemia. 1145 73

Sickle cell disease (SCD) is caused by a single point mutation in the human betaA globin gene that results in the formation of an abnormal hemoglobin [HbS (alpha2betaS2)]. We designed a betaA globin gene variant that prevents HbS polymerization and introduced it into a lentiviral vector we optimized for transfer to hematopoietic stem cells and gene expression in the adult red blood cell lineage. Long-term expression (up to 10 months) was achieved, without preselection, in all transplanted mice with erythroid-specific accumulation of the antisickling protein in up to 52% of total hemoglobin and 99% of circulating red blood cells. In two mouse SCD models, Berkeley and SAD, inhibition of red blood cell dehydration and sickling was achieved with correction of hematological parameters, splenomegaly, and prevention of the characteristic urine concentration defect.
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PMID:Correction of sickle cell disease in transgenic mouse models by gene therapy. 1174 72

Hydroxyurea represents an approved treatment for sickle cell anemia and acts as a nitric oxide donor under oxidative conditions in vitro. Electron paramagnetic resonance spectroscopy shows that hydroxyurea reacts with oxy-, deoxy-, and methemoglobin to produce 2-6% of iron nitrosyl hemoglobin. No S-nitrosohemoglobin forms during these reactions. Cyanide and carbon monoxide trapping studies reveal that hydroxyurea oxidizes deoxyhemoglobin to methemoglobin and reduces methemoglobin to deoxyhemoglobin. Similar experiments reveal that iron nitrosyl hemoglobin formation specifically occurs during the reaction of hydroxyurea and methemoglobin. Experiments with hydroxyurea analogues indicate that nitric oxide transfer requires an unsubstituted acylhydroxylamine group and that the reactions of hydroxyurea and deoxy- and methemoglobin likely proceed by inner-sphere mechanisms. The formation of nitrate during the reaction of hydroxyurea and oxyhemoglobin and the lack of nitrous oxide production in these reactions suggest the intermediacy of nitric oxide as opposed to its redox form nitroxyl. A mechanistic model that includes a redox cycle between deoxyhemoglobin and methemoglobin has been forwarded to explain these results that define the reactivity of hydroxyurea and hemoglobin. These direct nitric oxide producing reactions of hydroxyurea and hemoglobin may contribute to the overall pathophysiological properties of this drug.
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PMID:Iron nitrosyl hemoglobin formation from the reactions of hemoglobin and hydroxyurea. 1184 Dec 42

Sickle cell disease (SCD) is a term used to describe a group of genetic disorders of hemoglobin production characterized by a predominance of the abnormal hemoglobin known as hemoglobin S. Common acute complications of SCD in children requiring hospitalization include painful episodes, febrile illness, and splenic sequestration. The staff nurse has an important role in providing prompt treatment and instituting preventative measures to avoid the adverse clinical outcomes of SCD such as acute chest syndrome, severe anemia, cardiovascular instability, and bacterial sepsis. A basic understanding of the pathophysiology of vaso-occlusion, the immune system, hemolysis, and the spleen is essential in the care of a child during an acute complication of SCD. Additionally important are a knowledge of the genetics, pathophysiology, medical and nursing management, and a familiarity with patient and family education material relating to sickle cell disease.
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PMID:Care of the child with sickle cell disease: acute complications. 1202 71

Severe hypoxia occurs in patients with acute chest syndrome, and erythrocytapheresis has been shown to improve oxygenation. Patients with sickle cell anemia also have decreased baseline oxygen saturation values, but the effect of erythrocytapheresis on steady-state oxygenation has not been well studied. We investigated the changes in oxygen saturation versus hematocrit, fraction of hemoglobin A, and transfusion volume during 71 prophylactic erythrocytapheresis procedures performed in 5 stable patients with sickle cell anemia. Each patient had a history of either acute chest syndrome or stroke, but no serious events occurred while enrolled in the chronic exchange program. The oxygen saturation improved from 1% to 6% during erythrocytapheresis in each of our patients (p < 0.001) regardless of preprocedure saturation level or total hematocrit. We have shown that decreased baseline oxygen saturation in sickle cell disease is related to abnormal hemoglobin S levels, and oxygen saturation can be improved with erythrocytapheresis, independent of any change in the total hematocrit.
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PMID:Oxygen saturation and hemoglobin A content in patients with sickle cell disease undergoing erythrocytapheresis. 1242 35

Central to the pathophysiology of sickle cell disease are the vaso-occlusive events that lead to tissue damages and life-threatening complications. Lungs are particularly vulnerable to vaso-occlusion because of their specific vasculature. We developed a mouse model of hypoxia/reoxygenation lung injury closely mimicking the lung pathology of patients with sickle cell disease. This model involves the exposure of transgenic sickle cell (SAD) mice to hypoxia (8% oxygen) for 4, 10, and 46 hours followed by 2 hours of reoxygenation. Gene expression profiling of SAD lung tissue pointed to the specific induction of genes involved in the response to ischemic stress and microcirculation remodeling: Hspcb, Hsp86-1, Nfe2l2, Ace, and Fgf7. Hypoxia/reoxygenation also induced a marked increase in bronchoalveolar (BAL) total leukocyte and neutrophil counts, BAL total protein content, and BAL tumor necrosis factor alpha (TNF-alpha), interleukin 6 (IL-6), IL-1alpha, and macrophage inflammatory protein 2 (MIP-2) levels, all indicators of enhanced inflammatory response as compared with control mice. Nitric oxide (NO) was administered to SAD mice. NO (40 ppm) inhalation protected SAD mice from the histopathologic lesions of ischemic/reperfusion lung injury with corresponding normalization and/or modulation of tissue gene expression profiles. Inhaled NO (1) significantly reduced the increase in BAL total protein content, BAL total leukocyte, and neutrophil counts; (2) modulated BAL cytokine network; and (3) did not affect hemoglobin and methemoglobin levels. The present study provides evidences for the beneficial effects of inhaled NO in pulmonary injury induced by hypoxia/reoxygenation in a mouse model of sickle cell disease (SCD) and opens new avenues in drug design based on tissue gene expression profiling.
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PMID:Inhaled nitric oxide protects transgenic SAD mice from sickle cell disease-specific lung injury induced by hypoxia/reoxygenation. 1268 31

A brief survey of abnormal hemoglobin variants among the major ethnic groups of Karachi was conducted; 202,600 subjects were studied. Patients with low hemoglobin (Hb), low mean cell volume (MCV) and mean cell hemoglobin (MCH) including anemia, microcytosis, hypochromic hemolysis and target cells, were refered for the identification of hemoglobinopathy by molecular methods. Population screening showed that 60% had iron-deficiency anemia and 40% had hemolytic anemia, of which 20.6% was due to beta-thalassemia major, 13% beta-thalassemia trait, 5.1% sickle cell disease, 0.76% hemoglobin D Punjab (HbD Punjab), 0.32% hemoglobin C (HbC), and 0.22% hereditary persistence of fetal hemoglobin (HPFH).
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PMID:Hemoglobinopathies among five major ethnic groups in Karachi, Pakistan. 1275 39

Although it has been shown that hydroxyurea (HU) therapy produces measurable amounts of nitric oxide (NO) metabolites, including iron nitrosyl hemoglobin (HbNO) in patients with sickle cell disease, the in vivo mechanism for formation of these is not known. Much in vitro data and some in vivo data indicates that HU is the NO donor, but other studies suggest a role for nitric oxide synthase (NOS). In this study, we confirm that the NO-forming reactions of HU with hemoglobin (Hb) or other blood constituents is too slow to account for NO production measured in vivo. We hypothesize that, in vivo, HU is partially metabolized to hydroxylamine (HA), which quickly reacts with Hb to form methemoglobin (metHb) and HbNO. We show that addition of urease, which converts HU to HA, to a mixture of blood and HU, greatly enhances HbNO formation.
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PMID:Urease enhances the formation of iron nitrosyl hemoglobin in the presence of hydroxyurea. 1288 Sep 48


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