scholarly journals Prenatal diagnosis of hemoglobinopathies: comparison of the results obtained by isoelectric focusing of hemoglobins and by chromatography of radioactive globin chains

Blood ◽  
1980 ◽  
Vol 56 (6) ◽  
pp. 1092-1099
Author(s):  
A Dubart ◽  
M Goossens ◽  
Y Beuzard ◽  
N Monplaisir ◽  
U Testa ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Isoelectric Focusing ◽  
Beta Thalassemia ◽  
Cell Disease ◽  
Globin Chains ◽  
Chain Synthesis ◽  
Comparison Of The Results ◽  
Selective Lysis ◽  
Globin Chain Synthesis

Isoelectric focusing (IEF) of hemoglobin was compared to the classical chromatography of labeled globin chains for 22 antenatal diagnoses of hemoglobinopathies: 11 for beta thalassemia, and 11 for sickle cell disease. In all cases, the two methods gave identical results. The diagnosis was confirmed after birth or abortion. Three fetuses homozygous for beta thalassemia and one homozygous for sickle cell disease exhibited no Hb A by IEF, in contrast to normal fetuses or those heterozygous for one of the two hemoglobinopathies. In addition, blood samples obtained in other centers after abortion of 22 fetuses homozygous for beta + or beta 0 thalassemia exhibited no Hb A when analyzed by IEF. When Hb A was present, the respective proportions of Hb A and acetylated Hb F were determined by densitometry of the IEF gel. The Hb A/acetylated Hb F ratio obtained by IEF correlated well with the beta A/gamma ratio of globin chain synthesis, IEF requires 0.1 mg of unlabeled hemoglobin. It is performed in 90 min and several samples can be analyzed simultaneously. If present, maternal contamination of fetal blood must be eliminated by selective lysis of maternal (RBC) using the Orskov reaction. Improvements in this method to obtain suitable samples for IEF analysis are described.

scholarly journals Prenatal diagnosis of hemoglobinopathies: comparison of the results obtained by isoelectric focusing of hemoglobins and by chromatography of radioactive globin chains

Blood ◽  
1980 ◽  
Vol 56 (6) ◽  
pp. 1092-1099 ◽  
Author(s):  
A Dubart ◽  
M Goossens ◽  
Y Beuzard ◽  
N Monplaisir ◽  
U Testa ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Isoelectric Focusing ◽  
Beta Thalassemia ◽  
Cell Disease ◽  
Globin Chains ◽  
Chain Synthesis ◽  
Comparison Of The Results ◽  
Selective Lysis ◽  
Globin Chain Synthesis

Abstract Isoelectric focusing (IEF) of hemoglobin was compared to the classical chromatography of labeled globin chains for 22 antenatal diagnoses of hemoglobinopathies: 11 for beta thalassemia, and 11 for sickle cell disease. In all cases, the two methods gave identical results. The diagnosis was confirmed after birth or abortion. Three fetuses homozygous for beta thalassemia and one homozygous for sickle cell disease exhibited no Hb A by IEF, in contrast to normal fetuses or those heterozygous for one of the two hemoglobinopathies. In addition, blood samples obtained in other centers after abortion of 22 fetuses homozygous for beta + or beta 0 thalassemia exhibited no Hb A when analyzed by IEF. When Hb A was present, the respective proportions of Hb A and acetylated Hb F were determined by densitometry of the IEF gel. The Hb A/acetylated Hb F ratio obtained by IEF correlated well with the beta A/gamma ratio of globin chain synthesis, IEF requires 0.1 mg of unlabeled hemoglobin. It is performed in 90 min and several samples can be analyzed simultaneously. If present, maternal contamination of fetal blood must be eliminated by selective lysis of maternal (RBC) using the Orskov reaction. Improvements in this method to obtain suitable samples for IEF analysis are described.

scholarly journals Hydroxyurea increases hemoglobin F levels and improves the effectiveness of erythropoiesis in beta-thalassemia/hemoglobin E disease

Blood ◽  
1996 ◽  
Vol 87 (3) ◽  
pp. 887-892 ◽  
Author(s):  
S Fucharoen ◽  
N Siritanaratkul ◽  
P Winichagoon ◽  
J Chowthaworn ◽  
W Siriboon ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Beta Thalassemia ◽  
Limited Information ◽  
Cell Disease ◽  
Hemoglobin F ◽  
Hemoglobin E ◽  
Globin Chains ◽  
Hb E ◽  
Alpha Globin

Hydroxyurea (HU) is one of several agents that have been shown to enhance hemoglobin (Hb) F levels in patients with sickle cell disease and may be useful as a therapy for beta-globinopathies. However, limited information exists on the effects of HU in patients with thalassemia. Accordingly, we examined the hematologic effects of orally administered HU in 13 patients with beta-thalassemia/Hb E, including four patients who had been splenectomized. These patients were treated with escalating doses (final range, 10 to 20 mg/kg/d) for 5 months and were observed in the outpatient hematology clinic every 2 to 4 weeks. Complete blood counts including reticulocyte counts, amounts of Hb E and Hb F, G gamma:A gamma and alpha:non-alpha globin biosynthetic ratios were evaluated before and during treatment. Almost all patients responded with an average increase of 33% in Hb F levels, from a mean (+/- SD) of 42% +/- 11% to 56% +/- 8% (P < .0001), and a reciprocal decline in the percentage of Hb E from 59% +/- 9% to 49% +/- 8% (P < .001). Reticulocytosis was decreased from a mean (+/- SD) of 18.0% +/- 15.6% to 11.7% +/- 9.1% (P < .05); there was also a slight (10%) but statistically significant increase in hemoglobin levels and an improved balance in alpha:non-alpha globin chains ratios. The side effects were minimal in most patients, although these patients tended to tolerate a lower dose of HU before significant myelosuppression than has been our previous experience in sickle cell disease. One splenectomized patient died of sepsis during the trial. We conclude that increased Hb F production in beta-thalassemia/Hb E patients, with an improvement in the alpha:non-alpha globin ratios and, probably, the effectiveness of erythropoiesis, can be achieved using HU. Longer trials of HU in this population, including at other doses and in combination with other agents, appear warranted.

Hemoglobinopathies and Sickle Cell Disease

2020 ◽  
Keyword(s):  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Single Gene ◽  
Globin Gene ◽  
Cell Disease ◽  
Key Points ◽  
Chain Synthesis ◽  
Treatment Use ◽  
Globin Chain Synthesis ◽  
Iron Chelating Agents

Key Points Inherited hemoglobin disorders account for most common single-gene defect in humans.Thalassemias are caused by mutations in the globin gene cluster, resulting in a decrease in globin chain synthesis while structural hemoglobinopathies usually result from a point mutation in the α- or β-globin gene that causes a functional abnormality.High-performance liquid chromatography has become the test of choice for the diagnosis of thalassemias and hemoglobinopathies because it reliably separates different hemoglobins.Newborn screening has helped with early diagnosis and management, thus decreasing morbidity and improving longevity.Blood transfusion, and appropriate use of iron chelating agents are mainstay of the treatment. Use of appropriate antibiotic prophylaxis starting from the neonatal period and appropriate vaccinations have decreased morbidity and improved survival in patients with sickle cell disease.

scholarly journals Hydroxyurea Treatment for Sickle Cell Disease

2002 ◽  
Vol 2 ◽  
pp. 1706-1728 ◽  
Author(s):  
Martin H. Steinberg
Keyword(s):  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Fetal Hemoglobin ◽  
Hemoglobin Concentration ◽  
Pharmacologic Therapy ◽  
Acute Chest Syndrome ◽  
Cell Disease ◽  
Globin Chains ◽  
Hydroxyurea Treatment ◽  
Erythroid Precursors

High fetal hemoglobin (HbF) levels inhibit the polymerization of sickle hemoglobin (HbS) and reduce the complications of sickle cell disease. Pharmacologic agents that can reverse the switch from γ- to β-chain synthesis — γ-globin chains characterize HbF, and sickle β-globin chains are present in HbS — or selectively increase the proportion of adult erythroid precursors that maintain the ability to produce HbF are therapeutically useful. Hydroxyurea promotes HbF production by perturbing the maturation of erythroid precursors. This treatment increases the total hemoglobin concentration, reduces the vaso-occlusive complications of pain and acute chest syndrome, and attenuates mortality in adults. It is a promising beginning for pharmacologic therapy of sickle cell disease. Still, its effects are inconsistent, trials in infants and children are ongoing, and its ultimate value — and peril — when started early in life are still unknown.

Haemoglobinopathies

2013 ◽  
pp. 1466-1470
Author(s):  
David Rees
Keyword(s):  
Bone Marrow ◽  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Lupus Erythematosus ◽  
Single Gene ◽  
Globin Genes ◽  
Globin Chain ◽  
Cell Disease ◽  
Chain Synthesis ◽  
Marrow Expansion

Inherited abnormalities of the globin genes are the commonest single-gene disorders in the world and fall into two main groups: thalassaemias and sickle cell disease. Thalassaemias are due to quantitative defects in globin chain synthesis which cause variable anaemia and ineffective erythropoiesis. Thalassaemia was initially thought to be a disease of the bones due to uncontrolled bone marrow expansion causing bony distortion, although this is now unusual with appropriate blood transfusions. Osteopenia, often severe, is a feature of most patients with thalassaemia major and intermedia, caused by bone marrow expansion, iron overload, endocrinopathy, and iron chelation. Treatment with bisphosphonates is generally recommended. Other rheumatological manifestations include arthropathy associated with the use of the iron chelator deferiprone. Sickle cell disease involves a group of conditions caused by polymerization of the abnormal -globin chain, resulting in abnormal erythrocytes which cause vaso-occlusion, vasculopathy, and ischaemic tissue damage. The characteristic symptom is acute bone pain caused by vaso-occlusion; typical episodes require treatment with opiate analgesia and resolve spontaneously by 5 days with no lasting bone damage. The frequency of acute episodes varies widely between patients. The incidence of osteomyelitis is increased, particularly with salmonella, although it is much rarer than acute vaso-occlusion. Avascular necrosis can affect the hips, and less commonly the shoulders and knees. Coincidental rheumatological disease sometimes complicates the condition, particularly systemic lupus erythematosus (SLE) which is more prevalent in populations at increased risk of sickle cell disease.

Laparoscopic cholecystectomy in adult patients with beta-thalassemia or sickle cell disease

2005 ◽  
Vol 19 (12) ◽  
pp. 1668-1669 ◽  
Author(s):  
G. Marakis ◽  
T. E. Pavlidis ◽  
K. Ballas ◽  
S. Rafailidis ◽  
A. Sakantamis
Keyword(s):  
Laparoscopic Cholecystectomy ◽  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Adult Patients ◽  
Beta Thalassemia ◽  
Cell Disease

scholarly journals Globin chain synthesis in HbD (Punjab)-beta-thalassemia

Blood ◽  
1976 ◽  
Vol 47 (1) ◽  
pp. 113-120 ◽  
Author(s):  
RF Rieder
Keyword(s):  
Bone Marrow ◽  
Peripheral Blood ◽  
Beta Thalassemia ◽  
Globin Chain ◽  
Globin Chains ◽  
Mild Anemia ◽  
Thalassemia Trait ◽  
Chain Synthesis ◽  
Hbd Punjab ◽  
Globin Chain Synthesis

Abstract A 23-yr-old man of Greek-Italian ancestry with mild anemia was found to be heterozygous for HbD (Punjab) beta121 glu leads to gin and beta- thalassemia. HbA was not detected upon electrophoresis of the subject's hemolysate, and no synthesis of betaA globin was demonstrated after incubation of peripheral blood or bone marrow with 3H-leucine. The thalassemia gene was thus of the betao variety. The betaD/alpha synthesis ratios were almost equally unbalanced in the blood and bone marrow: 0.53 and 0.61, respectively. The mother of the propositus had beta-thalassemia trait. In peripheral blood the betaA/alpha synthesis ratio was 0.38. The mutant betaD gene thus appeared potentially capable of directing the synthesis of globin chains as efficiently as a normal betaA gene. The mildness of the HbD-betao-thalassemia syndrome appeared to be due to the maintenance of a relatively high total beta/alpha synthesis ratio in the presence of a physiologically neutral structural mutation.

scholarly journals Clinical events in the first decade in a cohort of infants with sickle cell disease. Cooperative Study of Sickle Cell Disease [see comments]

Blood ◽  
1995 ◽  
Vol 86 (2) ◽  
pp. 776-783 ◽  
Author(s):  
FM Gill ◽  
LA Sleeper ◽  
SJ Weiner ◽  
AK Brown ◽  
R Bellevue ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Sickle Cell ◽  
Clinical Course ◽  
The United States ◽  
Beta Thalassemia ◽  
Acute Chest Syndrome ◽  
Cooperative Study ◽  
Cell Disease ◽  
Splenic Sequestration ◽  
Clinical Events

Within the Cooperative Study of Sickle Cell Disease, 694 infants with confirmed sickle cell disease were enrolled at less than 6 months of age. Information about the nature and frequency of complications was collected prospectively over a 10-year period. Painful crises and acute chest syndrome were the most common sickle cell-related events in homozygous sickle cell anemia (SS), hemoglobin SC disease (SC), and S beta thalassemia patients (overall incidence in SS patients of 32.4 and 24.5 cases per 100 person-years, respectively). Bacteremia occurred most frequently in SS children under 4 years of age and in SC patients less than 2 years of age. The mortality rate was low in this cohort compared with that found in previous reports. Twenty children, all with Hb SS, died (1.1 deaths per 100 person-years among SS patients). Infection, most commonly with Streptococcus pneumoniae and Hemophilus influenzae, caused 11 deaths. Two children died of splenic sequestration, 1 of cerebrovascular accident, and 6 of unclear causes. Two patients underwent cholecystectomies, and 17 underwent splenectomies after one or more splenic sequestration crises. The experience of this cohort should reflect closely the true clinical course of those children with Hb SS and Hb SC disease who are observed in sickle cell centers in the United States.

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