Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0002874 (aplastic anemia)
 5,905 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A 16-yr-old male patient with hemochromatosis due to multiple packed red blood cell transfusions was referred to our emergency center for the treatment of severe aplastic anemia and dyspnea. He was diagnosed with aplastic anemia at 11-yr of age. He had received continuous transfusions because an HLA-matched marrow donor was unavailable. Following a continuous, approximately 5-yr transfusion, he was noted to develop hemochromatosis. He had a dilated cardiomyopathy and required diuretics and digitalis, multiple endocrine and liver dysfunction, generalized bleeding, and skin pigmentation. A total volume of red blood cell transfusion before deferoxamine therapy was about 96,000 mL. He received a regular iron chelation therapy (continuous intravenous infusion of deferoxamine, 50 mg/kg/day for 5 days q 3-4 weeks) for approximately seven years after the onset of multiple organ failures. His cytopenia and organ dysfunctions began to be gradually recovered since about 2002, following a 4-yr deferoxamine treatment. He showed completely normal ranges of peripheral blood cell counts, heart size, and liver function two years ago. He has not received any transfusions for the last four years. This finding suggests that a continuous deferoxamine infusion may play a role in the immune regulation in addition to iron chelation effect.
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PMID:Complete hematopoietic recovery after continuous iron chelation therapy in a patient with severe aplastic anemia with secondary hemochromatosis. 1843 19

The pharmacokinetics (PK) and pharmacodynamics (PD) of the once-daily, oral ironchelating agent, deferasirox (Exjade, ICL670), have been evaluated further in a Phase I, openlabel, multicenter, dose-escalation study in Japanese patients with myelodysplastic syndromes, aplastic anemia, and other anemias. Deferasirox was initially administered as a single dose of 5 (n = 6), 10 (n = 7), 20 (n = 6) or 30 (n = 7) mg/(kg day) and then after 7 days seven daily doses were administered. Linear PK (C (max) and AUC) were observed at all doses after a single dose and at steady state, and dose-dependent iron excretion was observed. Pharmacokinetic/pharmacodynamic parameters were similar to those reported in a Caucasian beta-thalassemia cohort. Following the single- and multiple-dose phases, 21 of 26 patients progressed to a 3-year extension phase of the study, where dose reductions and increases [5-30 mg/(kg day)] were allowed following safety and efficacy assessments. In the interim, 1-year data show that deferasirox was well tolerated, with generally infrequent and mild adverse events. Reductions in serum ferritin levels were observed and a negative iron balance achieved at doses of 20-30 mg/(kg day). These data suggest that deferasirox has a stable and predictable PK/PD profile, irrespective of underlying disease or race, and a predictable and manageable safety profile suitable for chronic administration.
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PMID:A safety, pharmacokinetic and pharmacodynamic investigation of deferasirox (Exjade, ICL670) in patients with transfusion-dependent anemias and iron-overload: a Phase I study in Japan. 1859 54

Emerging clinical data indicate that transfusion-dependent patients with bone marrow-failure syndromes (BMFS) are at risk of the consequences of iron overload, including progressive damage to hepatic, endocrine, and cardiac organs. Despite the availability of deferoxamine (DFO) in Korea since 1998, data from patients with myelodysplastic syndromes, aplastic anemia, and other BMFS show significant iron overload and damage to the heart and liver. The recent introduction of deferasirox, a once-daily, oral iron chelator, may improve the availability of iron chelation therapy to iron-overloaded patients, and improve compliance in patients who may otherwise find adherence to the DFO regimen difficult.
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PMID:Iron chelation therapy in the myelodysplastic syndromes and aplastic anemia: a review of experience in South Korea. 1860 81

Recent studies have suggested that the presence of iron overload prior to stem cell transplantation is associated with decreased survival. Within these studies, the criteria used to define iron overload have varied considerably. Given the lack of consensus regarding the definition of iron overload in the transplant setting, we sought to methodically examine iron status among transplant patients. We studied 78 consecutive patients at risk for transfusion-related iron overload (diagnoses included AML, ALL, MDS, and aplastic anemia) who received either autologous or allogeneic stem cell transplant. Multiple measures of iron status were collected prior to transplantation and examined for their association with survival. Using this data, three potentially prognostic iron measures were identified and incorporated into a rational and unified scoring system. The resulting Transplant Iron Score assigns a point for each of the following variables: (1) greater than 25 red cell units transfused prior to transplantation; (2) serum ferritin > 1000 ng/ml; and (3) a semi-quantitative bone marrow iron stain of 6+. In our cohort, the score (range 0 to 3) was more closely associated with survival than any available single iron parameter. In multivariate analysis, we observed an independent effect of iron overload on transplant survival (p = 0.01) primarily attributable to an increase in early treatment-related deaths (p = 0.02) and lethal infections. In subgroup analysis, the predictive power of the iron score was most pronounced among allogeneic transplant patients, where a high score (> or = 2) was associated with a 50% absolute decrease in survival at one year. In summary, our results lend further credence to the notion that iron overload prior to transplant is detrimental and suggest iron overload may predispose to a higher rate of lethal infections.
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PMID:The transplant iron score as a predictor of stem cell transplant survival. 1985 46

Biological assay of the human liver in various types of anemia shows conspicuous differences in the concentration of hemoglobin producing factors. Pernicious anemia shows very high values and the liver in untreated cases may show maximal storage of the hemoglobin producing factors. Liver therapy reduces this store as the missing factor is supplied and new hemoglobin and red cells can be turned out by the marrow. Aplastic anemia likewise shows high concentration of hemoglobin producing factors as there is no outlet for this material through the red marrow. Secondary anemia due to loss of blood will show low normal values but even long standing severe anemia will not seriously deplete this store of hemoglobin producing factors in the liver. Secondary anemia due to blood destruction within the body shows higher values and some excess store of hemoglobin producing factors and iron. Leukemia gives a biological assay like secondary anemia due to blood loss and always presents definite anemia. Iron analyses show conspicuous differences and iron concentration within the liver parenchyma does not in any way parallel the concentration of hemoglobin producing factors. The highest values for iron concentration are found in aplastic anemia (70 mg. per cent)- high values in pernicious anemia (51 mg. per cent)-normal values in leukemia (13 mg. per cent)-and low values in anemia due to loss of blood (5.3 mg. per cent). These findings should aid in a more complete understanding of the pathogenesis and internal metabolism of various anemias.
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PMID:HEMOGLOBIN PRODUCTION FACTORS IN THE HUMAN LIVER : III. ANEMIAS-PRIMARY, APLASTIC AND SECONDARY-LEUKEMIAS. 1987 Jan 54

Human liver tissue has been assayed to determine the amount of hemoglobin production factors in normal and abnormal states. Standardized dogs made anemic by blood removal have been used in this biological assay. Normal animal liver as control is rated as 100 per cent. Normal human liver tissue as compared with the normal animal control contains more of these hemoglobin production factors-a biological assay ratio of 120 to 160 per cent. Infections, acute and chronic, do not appear to modify these values, the concentration of hemoglobin-producing factors falling within the normal range. Pernicious anemia and aplastic anemia both show large liver stores of hemoglobin-producing factors-a biological assay ratio of 200 to 240 per cent. Therapy in pernicious anemia reduces these liver stores as new red cells are formed. Secondary anemia presents a low normal or subnormal liver store of hemoglobin-producing factors-an assay of 60 to 130 per cent. Hemochromatosis, erythroblastic anemia, and hemolytic icterus in spite of large iron deposits in the liver usually show a biological assay which is normal or close to normal. Polycythemia shows low reserve stores of hemoglobin-producing factors. Leukemias present a wide range of values discussed above. Hypoproteinemia almost always is associated with low reserve stores of hemoglobin-producing factors in the liver-biological assays of 60 to 80 per cent. Hypoproteinemia means a depletion of body protein reserve stores including the labile protein liver reserves-a strong indication that the prehemoglobin material (or globin) is related to these liver stores. Pregnancy, eclampsia, and lactation all may present subnormal liver stores of hemoglobin-producing factors. Exhaustion of protein stores lowers the barrier to infection and renders the liver very susceptible to many toxic substances. It should not be difficult to correct hypoproteinemia under these conditions and thus relieve the patient of a real hazard.
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PMID:HEMOGLOBIN PRODUCTION FACTORS IN THE HUMAN LIVER : ANEMIAS, HYPOPROTEINEMIA, CIRRHOSIS, PIGMENT ABNORMALITIES, AND PREGANCY. 1987 Dec 36

Deferasirox is a once-daily oral iron chelator with established dose-dependent efficacy in both adult and pediatric patients with transfusional iron overload. The clinical development program has demonstrated the efficacy of deferasirox for up to 4.5 years of treatment in patients with various underlying anemias, including beta-thalassemia, myelodysplastic syndromes, sickle cell disease, aplastic anemia, and other rare anemias. In addition to reducing key indicators of total body iron levels (serum ferritin, liver iron concentration, and toxic labile plasma iron), deferasirox has also demonstrated the ability to remove cardiac iron and prevent future cardiac iron accumulation. Emerging long-term data confirm the tolerability profile of deferasirox, and data on patient compliance render deferasirox a suitable therapeutic option for patients with chronic conditions requiring ongoing iron chelation therapy. Data continue to accumulate in a wide range of patient groups, including those with non-transfusion-dependent anemias such as hereditary hemochromatosis.
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PMID:Deferasirox (Exjade) for the treatment of iron overload. 1990 54

To clarify whether measurement of serum haptoglobin (Hp) has impact on understanding pathophysiology in bone marrow failure (BMF) syndromes, we investigated concentrations of serum Hp by nephelometric procedure in 156 Japanese patients with BMF, including 54 aplastic anemia (AA), 50 paroxysmal nocturnal hemoglobinuria (PNH), and 52 myelodysplastic syndromes (MDS) patients. The frequencies with low concentrations of serum Hp (<42 mg/dL) in PNH patients (98.0%) were significantly higher than those in AA (27.8%; P < 0.0001) and MDS (38.5%; P < 0.0001) patients. In AA patients, white blood cell (WBC), absolute neutrophil, and platelet counts were significantly decreased in the group (n = 15) with low concentrations of serum Hp than in that (n = 39) with normal concentrations of it, and WBC counts were positively correlated with concentrations of serum Hp, suggesting that WBC counts may affect the concentrations. In MDS patients, hemoglobin concentrations and serum iron were significantly decreased and increased, respectively, in the group (n = 20) with low concentrations of serum Hp than in that (n = 32) with normal concentrations of it, and the values of serum iron were inversely correlated with concentrations of serum Hp, suggesting that ineffective erythropoiesis may affect the concentrations. Several AA and MDS patients with low concentrations of serum Hp had Coombs-negative autoimmune hemolytic anemia determined by immunoradiometric assay. In conclusion, several factors in conjunction with pathophysiology contribute to decrease of serum Hp in BMF.
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PMID:Low concentration of serum haptoglobin has impact on understanding complex pathophysiology in patients with acquired bone marrow failure syndromes. 2037 81

Beta-thalassemias are a group of hereditary blood disorders characterized by anomalies in the synthesis of the beta chains of hemoglobin resulting in variable phenotypes ranging from severe anemia to clinically asymptomatic individuals. The total annual incidence of symptomatic individuals is estimated at 1 in 100,000 throughout the world and 1 in 10,000 people in the European Union. Three main forms have been described: thalassemia major, thalassemia intermedia and thalassemia minor. Individuals with thalassemia major usually present within the first two years of life with severe anemia, requiring regular red blood cell (RBC) transfusions. Findings in untreated or poorly transfused individuals with thalassemia major, as seen in some developing countries, are growth retardation, pallor, jaundice, poor musculature, hepatosplenomegaly, leg ulcers, development of masses from extramedullary hematopoiesis, and skeletal changes that result from expansion of the bone marrow. Regular transfusion therapy leads to iron overload-related complications including endocrine complication (growth retardation, failure of sexual maturation, diabetes mellitus, and insufficiency of the parathyroid, thyroid, pituitary, and less commonly, adrenal glands), dilated myocardiopathy, liver fibrosis and cirrhosis). Patients with thalassemia intermedia present later in life with moderate anemia and do not require regular transfusions. Main clinical features in these patients are hypertrophy of erythroid marrow with medullary and extramedullary hematopoiesis and its complications (osteoporosis, masses of erythropoietic tissue that primarily affect the spleen, liver, lymph nodes, chest and spine, and bone deformities and typical facial changes), gallstones, painful leg ulcers and increased predisposition to thrombosis. Thalassemia minor is clinically asymptomatic but some subjects may have moderate anemia. Beta-thalassemias are caused by point mutations or, more rarely, deletions in the beta globin gene on chromosome 11, leading to reduced (beta+) or absent (beta0) synthesis of the beta chains of hemoglobin (Hb). Transmission is autosomal recessive; however, dominant mutations have also been reported. Diagnosis of thalassemia is based on hematologic and molecular genetic testing. Differential diagnosis is usually straightforward but may include genetic sideroblastic anemias, congenital dyserythropoietic anemias, and other conditions with high levels of HbF (such as juvenile myelomonocytic leukemia and aplastic anemia). Genetic counseling is recommended and prenatal diagnosis may be offered. Treatment of thalassemia major includes regular RBC transfusions, iron chelation and management of secondary complications of iron overload. In some circumstances, spleen removal may be required. Bone marrow transplantation remains the only definitive cure currently available. Individuals with thalassemia intermedia may require splenectomy, folic acid supplementation, treatment of extramedullary erythropoietic masses and leg ulcers, prevention and therapy of thromboembolic events. Prognosis for individuals with beta-thalassemia has improved substantially in the last 20 years following recent medical advances in transfusion, iron chelation and bone marrow transplantation therapy. However, cardiac disease remains the main cause of death in patients with iron overload.
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PMID:Beta-thalassemia. 2049 8

This review discusses aplastic anemia (AA), paroxysmal nocturnal hemoglobinuria (PNH) and the myelodysplastic syndrome (MDS, all diseases associated with severe anemia. Anemia in AA and MDS is mainly due to defective or lacking eryhtropoiesis in the case of PNH mostly due to hemolysis. Management by transfusions, the use of growth factors and iron chelation is being discussed as are more specific treatment approaches directed against the underlying disease.
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PMID:[Anemia with aplastic anemia, paroxysmal nocturnal hemoglobinuria and myelodysplastic syndromes]. 2050 22


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