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Query: UMLS:C0019045 (hemoglobinopathies)
 2,704 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The past decade has witnessed profound increases in knowledge of the structure, function, and developmental regulation of the human globin genes. This information has deepened our understanding of the molecular and cellular mechanisms underlying inherited disorders affecting hemoglobin, and it has provided a new perspective for attaining meaningful increases in fetal hemoglobin synthesis in the management of sickle cell anemia and beta thalassemia. Efforts to provide therapy for these disorders are based on three factors: an understanding of their pathophysiology; the potential for fetal hemoglobin to alter its manifestation; and the concept that developmental changes in globin gene expression might be reversed by manipulating cellular and molecular regulatory mechanisms. In this review we discuss these topics and examine critically recent efforts to apply various pharmacological agents to in vitro, animal, and human models with the goal of increasing HbF synthesis. Several agents have demonstrated activity in patients with hemoglobin disorders. One such agent, hydroxyurea, has been shown to be potentially efficacious in phase II clinical trials in patients with sickle cell anemia and awaits testing in a placebo-controlled phase III study.
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PMID:Therapeutic approaches to hemoglobin switching in treatment of hemoglobinopathies. 137

Priapism may be primary (idiopathic) or secondary to sickle cell anemia, trauma, leukemia, drugs, venous thromboembolic diseases, and other less common disorders. This study concerns 21 patients with priapism treated during a period of ten years. Nine patients (43%) had sickle cell anemia. Of the 12 individuals (57%) classified as idiopathic, 3 (25%) had previously undergone surgical splenectomy for benign conditions. Considering the propensity for this unusual condition to develop in patients with hemoglobinopathy-induced hyposplenism, the possibility of a relationship between the asplenic state and priapism is considered.
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PMID:Priapism associated with asplenic state. 141 61

Sickle hemoglobinopathies include sickle cell disease, sickle-C disease, and sickle-beta thalassemia. Patients with these disorders commonly suffer a multitude of destructive events to vital organs, especially to the central nervous system, the spleen, the kidney, the lung, and the heart as a result of microvascular plugging by the sickled erythrocytes. Thoughtful preparation for anesthesia and operation, especially when directed by experienced individuals, can greatly reduce the hazard of inducing the sickle crises that formerly plagued individuals with sickle hemoglobinopathies who faced major operations under general anesthesia. The patient must be free of any acute illness, especially one involving the respiratory system. Adequate hydration preoperatively combined with avoiding perioperative hypoxia, hypothermia, and acidosis, the triggers for sickling, will go far toward avoiding sickle-induced complications. Modern transfusion therapy, consisting of multiple small transfusions of Hb A erythrocytes administered over several weeks prior to the operation, not only corrects the chronic anemia but suppresses erythropoiesis of cells containing Hb S in the patient's bone marrow and leaves him or her with a majority of cells containing Hb A. This provides a safety net in case a sickle-inducing insult occurs despite the best efforts to avoid one. Individuals with sickle hemoglobinopathies may require any of the operations common to all children, for example, herniorrhaphy, appendectomy, tonsillectomy, and circumcision, but a significant number will develop calcium bilirubinate cholelithiasis and possibly cholecystitis as a result of the continual increased load of bile salts resulting from the shortened lifespan of the cells containing Hb S. Also, although most individuals with Hb S will gradually suffer splenic infarction by late childhood, a significant number of infants will experience acute splenic sequestration crisis, a life-threatening entity, the recurrence of which is prevented by splenectomy. Several publications have demonstrated that such surgical procedures can be performed in large numbers of patients with sickle hemoglobinopathies without deaths and with minimal morbidity.
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PMID:Surgical management of children with hemoglobinopathies. 144 Jan 54

Between 1970-1990, the Laboratory tested 38,391 specimens for hemoglobinopathies, of which 7,935 were positive. The major abnormalities detected were beta thalassemia trait (4,688), alpha thalassemia trait (1,248) and sickle cell trait (847). Clinically significant hemoglobinopathies detected were Hemoglobin H disease (100), sickle cell disease (67) and sickle cell Hemoglobin C disease (79). Hemoglobinopathies are therefore common in the Hamilton area as a reflection of the cultural diversity of area citizens. Of the 49 patients with thalassemia without documented iron deficiency, 8 (16%) received iron therapy for a variable period of time and 3 were investigated for gastrointestinal blood loss. Hemoglobin abnormalities cause or have the potential to cause clinical disease and they can, if not detected, result in unnecessary iron therapy or gastrointestinal investigation.
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PMID:The clinical significance of hemoglobinopathies in the Hamilton region: a twenty-year review. 145 12

Blood erythroid progenitors (BFU-E) from patients with sickle and thalassemic syndromes were compared with those from normal individuals. The day of maximal colony formation in methyl cellulose was slightly later in the cultures from the patients with hemoglobinopathies than in the normal cultures. The number of colonies/100,000 mononuclear cells was similar in all cultures on day 13, but was higher in the hemoglobinopathy cultures on the day of maximal growth. The number of BFU-E/mL of blood was significantly higher than normal at all times in both sickle cell anemia and thalassemia. The proportional synthesis of gamma globin was twice normal in all sickle cultures, and 4 times normal in those from beta+-thalassemia. Hemin and interleukin-3 increased the numbers of erythroid colonies in all cultures, but did not consistently alter the globin synthesis patterns. Each progenitor population has a unique pattern in terms of time course, number of BFU-E, and level of gamma globin synthesis. These features indicate distinct types of BFU-E, or differences in accessory cells, or both, which distinguish blood-borne erythropoiesis in normals and those with hemoglobinopathies.
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PMID:Sickle and thalassemic erythroid progenitor cells are different from normal. 148 17

We estimated incidence of HbS disease in Quebec. It is approximately 9 cases per 100,000 births (equivalent to the incidence of the hyperphenylalanemias). Accordingly, we performed a voluntary pilot study in 9 self-identified ethnic groups; 3528 families were counselled about the relevance of newborn screening for hemoglobinopathies; and 2779 cord blood samples were collected (participation rate, 78.7%) and analyzed for Hemoglobin S and other hemoglobin variants by cellulose acetate electrophoresis. There were 95 (3.42%) positive tests on the initial (cord blood) samples, of which only 40 could be confirmed because of low participation in follow-up. We identified 8 false-positive tests; 7 had been classified initially as alpha-thalassemia trait and one as HbC heterozygosity on the first test. The relative frequency of hemoglobinopathy genes (confirmed) was: 52.5% HbS; 22.5% alpha-thalassemia; 22.5% other mutation; all but one patient with sickle cell disease were heterozygotes; the majority (71%) of HbS genes were accounted for by the 7% of screened newborns who were Black; a further 24% of the HbS genes were accounted for by 7% with Central American ancestry. Record linkage of the findings in heterozygotes for use later in life is an unsolved problem. Seventy five first-degree relatives of the 48 probands were screened in follow-up studies (64% of parents participated); 5 couples at risk for having a future child with a hemoglobinopathy were identified. Attitudes toward follow-up varied among the ethnic groups. The single family with an affected newborn (sickle cell anemia) was counselled effectively; the infant received penicillin prophylaxis.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Newborn screening for sickle cell and other hemoglobinopathies: a Canadian pilot study. 151 95

Standard electrophoretic methods for the diagnosis of hemoglobinopathies are confounded in individuals chronically transfused. We present the accurate diagnosis of sickle cell disease in two such transfused patients by the application of polymerase chain reaction technology to analyze patient's hemoglobin beta-chain genes directly.
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PMID:Diagnosis of sickle cell disease in chronically transfused patients. 155 Feb 67

The frequency of glucose-6-phosphate dehydrogenase (G-6-PD) deficiency was determined in 54 male patients with sickle cell diseases: 31 sickle cell anemia (SS), 14 sickle cell hemoglobinopathy (SC) and 9 HbS/beta-thalassemia (S/B-thal) by a combination of quantitative assay, fluorescent spot test and electrophoresis. Of the 54 patients tested, 7 were found to be G-6-PD deficient (G-6-PD-) (3 SS, 3 SC and 1 S/B-thal) and 47 G-6-PD normal (G-6-PD+) (6 G-6-PD A and 41 G-6-PD B). All the deficient patients were G-6-PD A-. The frequency of G-6-PD deficiency did not differ significantly from that observed in the general population. Compared to patients who were not G-6-PD-, there were no significant differences in the hemoglobin concentration and reticulocyte count in patients with sickle cell diseases who were G-6-PD-.
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PMID:Glucose-6-phosphate dehydrogenase deficiency and sickle cell disease in Brazil. 157 71

The Committee on Infectious Diseases of the American Academy of Pediatrics, and the Advisory Committee on Immunization Practices of the Center for Disease Control for many years have recommended the routine use of influenza vaccine in various hemoglobinopathies including sickle cell disease. This recommendation, however, has not been included in the patient care protocols of the Comprehensive Sickle Cell Centers program of NIHLB. Most clinicians have not used yearly influenza vaccine for their patients with sickle cell disease. This article reports a case of a 5-year-old boy with sickle cell disease who had not received influenza vaccine. He developed pneumonitis and acute myositis during a serologically confirmed influenza B virus infection. The incapacitating and protracted course of his illness presented diagnostic and management problems. His case strongly supports the recommendation of the two infectious disease committees.
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PMID:Sickle cell disease with complicated influenza B virus infection. 160 65

The authors report about one case of left branchial arterial thrombosis in a 6-year-old child with thalassemia-sickle cell disease. In their opinion, although this hemoglobinopathy usually causes microthrombosis, its existence at the same time as that of the brachial thrombosis does not seem to be a coincidence. The actual origin of this disease remains to be found, as well as the role that thrombocytosis may play. The authors emphasize the relative rarity of thrombolytic arterial diseases in African Negroes and advise practitioners to recognize them, because their diagnosis, often established late in our climates, has severe consequences.
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PMID:[Acute thrombosis of the brachial artery and beta-thalassemia-sickle cell anemia]. 161 6


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