losartan-potassium and Spherocytosis--Hereditary

Topics: Blood Transfusion; Erythrocyte Count; Erythropoietin; Female; Follow-Up Studies; Hemoglobins; Humans; Infant; Infant, Newborn; Italy; Male; Recombinant Proteins; Reticulocytes; Retrospective Studies; Spherocytosis, Hereditary

Aquaporin-1 (AQP1) is the membrane water channel responsible for changes in erythrocyte volume in response to the tonicity of the medium. As the aberrant distribution of proteins in hereditary spherocytosis (HS) generates deficiencies of proteins other than those codified by the mutated gene, we postulated that AQP1 expression might be impaired in spherocytes. AQP1 expression was evaluated through flow cytometry in 5 normal controls, 1 autoimmune hemolytic anemia, 10 HS (2 mild, 3 moderate, 2 severe, and 3 splenectomized), and 3 silent carriers. The effect of AQP1 inhibitors was evaluated through water flow-based tests: osmotic fragility and hypertonic cryohemolysis. Serum osmolality was measured in 20 normal controls and 13 HS. The effect of erythropoietin (Epo) on AQP1 expression was determined in cultures of erythroleukemia UT-7 cells, dependent on Epo to survive. Independent of erythrocyte size, HS patients showed a lower content of AQP1 in erythrocyte membranes which correlated with the severity of the disease. Accordingly, red blood cells from HS subjects were less sensitive to cryohemolysis than normal erythrocytes after inhibition of the AQP1 water channel. A lower serum osmolality in HS with respect to normal controls suggests alterations during reticulocyte remodeling. The decreased AQP1 expression could contribute to explain variable degrees of anemia in hereditary spherocytosis. The finding of AQP1 expression induced by Epo in a model of erythroid cells may be interpreted as a mechanism to restore the balance of red cell water fluxes.

Topics: Adolescent; Adult; Anemia, Hemolytic, Autoimmune; Aquaporin 1; Biological Transport; Body Water; Cell Line; Child; Child, Preschool; Erythrocyte Membrane; Erythrocytes; Erythropoietin; Gene Expression Regulation; Hemolysis; Heterozygote; Humans; Leukemia, Lymphocytic, Chronic, B-Cell; Middle Aged; Osmolar Concentration; Osmotic Fragility; Spherocytosis, Hereditary; Splenectomy

Hereditary Spherocytosis (HS) is a common haemolytic anaemia in which 75% of cases are autosomal dominant. As most newborns with HS have a family history of disease, haematologists often see these infants before their physiologic haemoglobin nadir, which is exaggerated in comparison with healthy infants. The objective of this study was to evaluate the frequency of implementation and cost of erythropoietin-stimulating agents (EPO) versus transfusion in infants with HS at a single paediatric programme. In the last decade, only 15% of infants with HS at our centre have been treated with EPO, which costs twice that of a single transfusion and EPO treated infants did not always avoid transfusion. Infrequent prescription of EPO therapy to infants with HS at our centre may be related to the incomplete data supporting its use.

Topics: Birth Weight; Erythrocyte Transfusion; Erythropoietin; Female; Gestational Age; Hematinics; Humans; Infant; Infant, Newborn; Male; Severity of Illness Index; Spherocytosis, Hereditary; Treatment Outcome

Hereditary spherocytosis (HS) is usually classified as mild, moderate or severe using conventional features, namely, hemoglobin (Hb) concentration, reticulocyte count and bilirubin levels, which do not always contribute to an adequate clinical classification. The aim of our study was to establish the importance of some laboratory routine parameters, as markers of HS clinical outcome, by studying a control group (n=26) and unsplenectomized HS patients (n=82) presenting mild, moderate or severe HS. We performed a basic hematologic study and evaluated the reticulocyte count, bilirubin, erythropoietin (EPO) and soluble transferrin receptor (sTfR) levels; the osmotic fragility (OFT) and criohemolysis tests (CHT); the ratios Hb/MCHC (mean cell hemoglobin concentration), Hb/RDW (red cell distribution width) and MCHC/RDW, were calculated. Hb changed significantly in accordance with HS severity, but not reticulocytes or bilirubin. We found that MCHC, RDW, EPO, sTfR, OFT, CHT and the calculated ratios were significantly changed in patients, and, therefore, were valuable as complementary diagnostic tools for HS. Moreover, RDW, Hb/MCHC, Hb/RDW and MCHC/RDW changed significantly with worsening of HS; thus, they are also good markers for the clinical outcome of HS. In conclusion, we propose the use of these routine parameters as useful to complement the analysis of HS severity.

Topics: Bilirubin; Biomarkers; Case-Control Studies; Erythrocyte Volume; Erythrocytes; Erythropoietin; Hemoglobins; Humans; Osmotic Fragility; Receptors, Transferrin; Reticulocyte Count; Reticulocytes; Severity of Illness Index; Spherocytosis, Hereditary

The course of hereditary spherocytosis (HS) may be subject to hemolytic episodes, sometimes requiring blood transfusion. The aim of this study was to evaluate the efficacy of a short course of steroid therapy in elevating hemoglobin levels during hemolytic crisis.. The files of all patients followed for HS from 1968 to 2009 at our hospital were reviewed. Outcome of hemolytic crises was compared between steroid-treated and untreated patients; patients given packed red blood cell transfusion(s) or erythropoietin treatment were excluded. A good outcome was defined as an increase of at least 20% in hemoglobin level from the nadir within 1 week.. Of the 118 patients with HS who attended our hospital during the study period, 20 were treated with steroids and 9 received no treatment. Mean nadir hemoglobin level in both groups was 6.9 g/dl. The study group had a total of 50 steroid-treated hemolytic crises of which 37 (74%) responded favorably to treatment. Treatment failure was significantly associated with a low dose (<1 mg/kg/day) or short duration (<1 week) of treatment. The nine untreated patients had 16 hemolytic crises, of which 25% had a good outcome. Steroid therapy was significantly more effective than no therapy in increasing hemoglobin level (P = 0.015) in these hemolytic crises.. Steroid therapy may be effective in augmenting hemoglobin levels during hemolytic crises in patients with moderate HS and eventually will result in a reduced need for RBC transfusion.

Topics: Child; Child, Preschool; Erythrocyte Transfusion; Erythropoietin; Female; Glucocorticoids; Hemoglobins; Humans; Logistic Models; Male; Multivariate Analysis; Osmotic Fragility; Prednisone; Retrospective Studies; Spherocytosis, Hereditary

Hereditary spherocytosis (HS) is the commonest inherited disorder of the erythrocyte membrane in Northern Europe and North America. It is marked by a regenerative anemia which varies widely from asymptomatic patients to severe hemolysis. In 75% of HS patients, inheritance is autosomal dominant. The diagnosis of HS is easily made when there are a family history, hemolytic anemia, reticulocytosis, spherocytes and increased hyperdense cells. Specialized testing to clarify the nature of membrane disorder is required when the film appearance is atypical without a positive family history, in the absence of a family history, in the newborn and before the splenectomy, to rule out the stomatocytosis which is contraindicated. The indication for splenectomy is dependent on the degree of anemia and its clinical manifestation.

Topics: Child; Cholecystectomy; Erythrocyte Membrane; Erythrocyte Transfusion; Erythropoietin; Humans; Recombinant Proteins; Spherocytosis, Hereditary; Splenectomy

Topics: Epoetin Alfa; Erythropoietin; Female; Hematinics; Hemoglobins; Humans; Infant, Newborn; Recombinant Proteins; Reticulocyte Count; Spherocytosis, Hereditary

Erythropoietin (EPO), the main growth factor responsible for the regulation of red blood cell production, may be overproduced when blood loss or haemolysis occurs. Patients with mild hereditary spherocytosis (HS) are able to maintain normal haemoglobin concentration, whereas typical and severe HS patients develop an anaemic state. Splenectomy usually reverses anaemia. We aimed to clarify the role of EPO in the response to enhanced spherocyte destruction, and to look for a linkage with the broad clinical spectra of HS. EPO levels, reticulocyte count and production index (RPI), other parameters used to classify HS and the protein deficiencies underlying HS were evaluated in previously diagnosed unsplenectomised (n = 24) and splenectomised (n = 10) patients presenting mild, typical or severe HS. A significant increase in EPO was observed in all unsplenectomised HS patients. In the mild form, a significant correlation of EPO with reticulocyte count and RPI was observed; however, this correlation disappeared in typical HS patients. Splenectomised HS patients presented a correction in EPO levels in all forms of HS, although the reticulocyte count and RPI sustained slightly higher values. Our data show HS as a disease linked to an overproduction of EPO, according to the severity of the disease; however, a disturbance in erythropoiesis seems to occur in typical HS. Moreover, splenectomy leads to a correction in the EPO levels.

Topics: Adult; Aged; Bilirubin; Blood Proteins; Child; Erythrocyte Membrane; Erythropoiesis; Erythropoietin; Humans; Membrane Proteins; Reticulocyte Count; Severity of Illness Index; Spherocytosis, Hereditary; Splenectomy

The newborn with hereditary spherocytosis can develop severe anemia, requiring red blood cell transfusions. Therapy with r-HuEPO has been proposed to avoid transfusions.. Hereditary spherocytosis was diagnosed in a newborn who had severe and early jaundice. He was treated with r-HuEPO, and did not require red blood cells transfusion.. Recombinant erythropoïetin might be an interesting alternative to red blood cells transfusions during the neonatal period in newborns with hereditary spherocytosis.

Topics: Drug Administration Schedule; Erythrocyte Transfusion; Erythropoietin; Hematocrit; Hemoglobins; Humans; Infant, Newborn; Injections, Subcutaneous; Jaundice, Neonatal; Male; Phototherapy; Recombinant Proteins; Reticulocyte Count; Spherocytosis, Hereditary; Time Factors; Treatment Outcome

Hereditary spherocytosis (HS) is a common inherited hemolytic anemia due to red cell membrane defects. Extramedullary hematopoiesis is a compensatory response to insufficient bone marrow blood cell production. The preferred sites of extramedullary hematopoietic involvement are the spleen, liver, and lymph nodes, but in HS the posterior paravertebral mediastinum is also commonly involved. A nonsplenectomized 74-year-old man with mild HS, with primary deficiency in ankyrin, was found by magnetic resonance imaging to have thoracic paravertebral hematopoietic masses. The patient showed high serum levels of erythropoietin, which may have played a role in the development of extramedullary hematopoietic masses through a continuous hematopoietic stimulus to erythroid cells in the propositus. The long-standing history of respiratory infections and of hypoxia in the propositus may have been an additional etiological factor.

Topics: Aged; Ankyrins; Erythropoietin; Hematopoiesis, Extramedullary; Humans; Magnetic Resonance Imaging; Male; Respiratory Tract Infections; Spherocytosis, Hereditary; Thorax

Hereditary spherocytosis is the most frequently occurring haemolytic anaemia. Some patients manifest clinical signs during the neonatal period and require transfusion. A case of hereditary spherocytosis in neonate is presented. The use of rhEPO during the first months may be an alternative therapy to red cell transfusion.

Topics: Erythrocyte Transfusion; Erythropoietin; Female; Hemoglobins; Humans; Infant; Infant, Newborn; Recombinant Proteins; Spherocytosis, Hereditary; Time Factors; Treatment Outcome

The goal of this study was to transfer by retroviral vector the cDNA for ankyrin to progenitors from normal bone marrow and from the nb/nb spherocytosis mutant deficient in expression of full-length ankyrin to achieve erythroid expression of functional ankyrin protein.. A minigene composed of the human ankyrin promoter, murine ankyrin cDNA, and the 3' human domain corresponding to the ankyrin 2.2 isoform was assembled in the retroviral vector, pG1. Murine erythroleukemia (MEL) cells, normal murine bone marrow cells, 3T3 fibroblasts, and nb/nb mutant bone marrow and spleen cells were transduced with the retroviral supernatant. Transduced mutant cells were induced to differentiate in liquid culture. Gene transfer was assessed by colony polymerase chain reaction (PCR) and reverse transcriptase (RT)-PCR, immunofluorescence, and Southern, Northern, and Western blot analysis.. MEL cells, normal bone marrow progenitors, and nb/nb cells were all successfully transduced and expressed ankyrin by RT-PCR and Western blot. Transduced murine 3T3 fibroblasts and MEL cells exhibited cell membrane staining by immunofluorescence. Colony RT-PCR demonstrated dependence of expression on erythropoietin. In vitro, the transduced nb/nb cells matured to polychromatophils, whereas nontransduced nb/nb cells matured to microspherocytes.. Retroviral transfer of ankyrin corrected the defect leading to formation of microspherocytes in erythroid differentiation cultures from the nb/nb mutant. The human ankyrin promoter conferred erythropoietin-dependent expression in normal and mutant erythroid progenitors, which could have implications for the gene therapy of human hemolytic anemias.

Topics: Animals; Ankyrins; Blotting, Western; Bone Marrow; Cell Line; Electrophoresis, Polyacrylamide Gel; Erythropoietin; Gene Transfer Techniques; Genetic Therapy; Hematopoietic Stem Cells; Humans; In Vitro Techniques; Mice; Mice, Inbred BALB C; Retroviridae; Reverse Transcriptase Polymerase Chain Reaction; Spherocytosis, Hereditary

In hereditary spherocytosis, erythropoiesis has been described as 'sluggish' during the first months of life. The lack of appropriate erythropoietic response to compensate for increased red cell destruction necessitates blood transfusions in 70-80% of hereditary spherocytosis-affected infants during their first year of life. After this period, less than 30% require regular transfusion support. This transient requirement for transfusion led us to wonder whether anemic hereditary spherocytosis infants, like anemic premature infants, could benefit from recombinant erythropoietin therapy (rHu-Epo).. In 16 hereditary spherocytosis infants (age range 16-119 days) with severe anemia, a compassionate open preliminary study was performed. rHu-Epo treatment (1000 IU/kg/week) was instituted together with iron supplementation. Hemoglobin values and reticulocyte counts were repeatedly assessed.. In 13 out of 16 infants, prompt increases in reticulocyte counts were noted after the first week of treatment with 1000 IU/kg/week of rHu-Epo. During treatment with Epo these infants maintained clinically acceptable levels of hemoglobin and did not require blood transfusions. As the infants grew and began to mount an adequate erythropoietic response, the rHu-Epo dose could be tapered and the treatment could be discontinued before the age of nine months.. Epo treatment in most hereditary spherocytosis infants appears to be effective in the management of anemia and could serve as a valuable alternative to packed RBC transfusions.

Topics: Blood Transfusion; Erythrocyte Transfusion; Erythropoietin; Female; Genomic Imprinting; Gestational Age; Hemoglobins; Humans; Infant; Infant, Newborn; Iron; Male; Recombinant Proteins; Reticulocyte Count; Spherocytosis, Hereditary

A 50-year-old man was admitted to our hospital for possible surgery. Echocardiogram showed severe calcification of the aortic valve, and cardiac catheter examination recorded a gradient greater than 150 mmHg across the valve. These results determined aortic valve replacement (AVR) to relieve the pressure-overloaded ventricle. Preoperative evaluations however, demonstrated anemia derived from hereditary spherocytosis (HS), an inherited hemolytic disorder. In order to avoid homologous blood transfusion, the following strategies were tried; 1) an iron supplement and an injection of recombinant human erythropoietin (rHuEPO); 2) pre- and perioperative autologous blood transfusion; and 3) an aggressive iron supplement just after the surgery. These raised the blood hemoglobin concentration to the criterion where autologous blood donation was started, and maintained the hemoglobin level stable, up to his discharge. In conclusion, bloodless cardiac surgery is possible for cases with anemia, and some strategies should be tried to raise and maintain the blood hemoglobin concentration well.

Topics: Aortic Valve; Aortic Valve Insufficiency; Blood Transfusion, Autologous; Drug Administration Routes; Drug Therapy, Combination; Echocardiography; Erythropoietin; Follow-Up Studies; Heart Valve Prosthesis Implantation; Hemoglobins; Humans; Intraoperative Period; Iron Compounds; Male; Middle Aged; Recombinant Proteins; Spherocytosis, Hereditary

A compensated haemolytic state is defined by decreased red cell life-span without anaemia, i.e. by increased erythropoiesis in the absence of the physiological stimulus for erythropoietin (Epo) production. We evaluated s-Epo levels and the expansion of erythropoiesis (as measured by circulating transferrin receptor, s-TfR) in 32 patients with hereditary spherocytosis (HS) with the aim of verifying whether the enhanced erythropoiesis of compensated haemolysis was Epo-dependent. 20 of the patients (62.5%) had normal Hb values (> 12 g/dl in females and > 13 g/dl in males). Their compensated haemolytic state was the result of up to 8.2 times normal s-Epo and up to 3.9 times normal s-TfR levels, which were maintained by physiological regulation of erythropoiesis, as documented by the inverse dependence of Hb on s-Epo levels. Considering that patients with iron-deficiency anaemia represented the predicted physiological Epo response to anaemia, the observed/predicted in s-Epo ratio (O/P ratio) was calculated in HS patients with anaemia and was used as an index of the adequateness of Epo production. All the anaemic HS patients had an O/P ratio > 1, documenting inappropriately high s-Epo levels. This work demonstrates that the compensated haemolytic state of HS patients is produced by an inappropriately high s-Epo level, and that the pattern of Epo overproduction is a biological characteristic of the disease.

Topics: Adolescent; Adult; Anemia, Iron-Deficiency; Child; Erythropoiesis; Erythropoietin; Female; Hemolysis; Humans; Male; Middle Aged; Receptors, Transferrin; Reference Values; Spherocytosis, Hereditary

Topics: Anemia, Hemolytic, Autoimmune; Erythropoiesis; Erythropoietin; Female; Humans; Kidney; Male; Oxygen; Spherocytes; Spherocytosis, Hereditary

Topics: Anemia, Hemolytic; Anemia, Hemolytic, Autoimmune; Anemia, Myelophthisic; Anemia, Sickle Cell; Bone Marrow; Erythropoietin; Heart Diseases; Hematocrit; Humans; Hypoxia; Kidney Diseases; Reticulocytes; Spherocytosis, Hereditary

Topics: Anemia, Hemolytic; Cholecystectomy; Erythrocyte Count; Erythropoiesis; Erythropoietin; Female; Hemoglobins; Humans; Iron; Male; Reticulocytes; Spherocytosis, Hereditary; Splenectomy; Splenomegaly