Fetal anemia and apoptosis of red cell progenitors in Stat5a-/-5b-/- mice: a direct role for Stat5 in Bcl-X(L) induction.
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The erythropoietin receptor (EpoR) is essential for production of red blood cells; a principal function of EpoR is to rescue committed erythroid progenitors from apoptosis. Stat5 is rapidly activated following EpoR stimulation, but its function in erythropoiesis has been unclear since adult Stat5a-/-5b-/- mice have normal steady-state hematocrit. Here we show that Stat5 is essential for the high erythropoietic rate during fetal development. Stat5a-/-5b-/- embryos are severely anemic; erythroid progenitors are present in low numbers, show higher levels of apoptosis, and are less responsive to Epo. These findings are explained by a crucial role for Stat5 in EpoR's antiapoptotic signaling: it mediates the immediate-early induction of Bcl-X(L) in erythroid cells through direct binding to the Bcl-X promoter. (+info)
Human immunodeficiency virus infection, anemia, and survival.
(42/4177)
Anemia, a common hematologic complication in human immunodeficiency virus (HIV)-infected patients, can be caused by mechanisms including infections, neoplasms, or drug treatment. Studies have consistently found anemia to be associated with reduced survival, even when potentially confounding factors were controlled for. Importantly, recovery from anemia has been shown to reduce this risk to approximately the same level as seen among patients never having had anemia. Although anemia traditionally has been treated with blood transfusions, recent studies have shown recombinant human erythropoietin (r-HuEPO) to be effective in elevating hematocrit values and reducing transfusion requirements in HIV-infected patients who have endogenous erythropoietin levels of < or = 500 IU/L. Therapy with r-HuEPO has been shown to be safe and well tolerated. In a recent study, moreover, receipt of erythropoietin was associated with a decreased risk of death, whereas transfusion was associated with an increased risk. If these results are confirmed, the link between r-HuEPO and decreased risk of death in HIV-infected patients with anemia will be further strengthened. (+info)
Prevalence of and factors associated with suboptimal care before initiation of dialysis in the United States.
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Despite improvements in dialysis care, the mortality of patients with end-stage renal disease (ESRD) in the United States remains high. Factors that thus far have received scant attention, but could significantly affect morbidity and mortality in dialysis patients, are the timing and quality of care before the initiation of dialysis (pre-ESRD). Data from the new version of the Health Care Financing Administration (HCFA) 2728 Form were used to examine the prevalence of and factors associated with hypoalbuminemia, severe anemia, and erythropoietin (EPO) use among 155,076 incident chronic dialysis patients in the United States between April 1, 1995 and June 30, 1997. At initiation of dialysis, the median serum albumin and hematocrit were 3.3 g/dl and 28%, respectively. Sixty percent of patients had a serum albumin below the lower limit of normal and 51% had a hematocrit <28%. Overall, only 23% had received EPO pre-ESRD. Among patients with hematocrit <28%, only 20% were receiving EPO, compared to 27% among patients with hematocrit > or =28%. In a multivariate analysis that adjusted for diabetes, functional status, and demographic, socioeconomic, and geographic factors, the odds ratios for hypoalbuminemia, hematocrit <28%, and lack of EPO use were higher for African-Americans, patients with non-private insurance or no insurance, and patients who were started on hemodialysis. There were also significant differences in odds ratios for these outcomes between different geographic regions in the United States. The high prevalence of pre-ESRD hypoalbuminemia, hematocrit <28%, and lack of EPO use suggests that the quality of pre-ESRD care in the United States is suboptimal. Improvement in pre-ESRD care could potentially improve outcomes among ESRD patients. (+info)
Dose dependent reduction of erythroid progenitor cells and inappropriate erythropoietin response in exposure to lead: new aspects of anaemia induced by lead.
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OBJECTIVE: To determine whether haematopoietic progenitor cells and erythropoietin (EPO), which is an essential humoral stimulus for erythroid progenitor (BFU-E) cell differentiation, are affected by lead intoxication. METHODS: In male subjects chronically exposed to lead with and without anaemia, pluripotent (CFU-GEMM), BFU-E and granulocyte/macrophage (CFU-GM) progenitor cell counts in peripheral blood were measured with a modified clonal assay. Lead concentrations in blood (PbB) and urine (PbU) were measured by the atomic absorption technique, and EPO was measured with a modified radioimmunoassay. RESULTS: PbB in the subjects exposed to lead ranged from 0.796 to 4.4 mumol/l, and PbU varied between 0.033 and 0.522 mumol/l. In subjects exposed to lead with PbB > or = 2.896 mumol/l (n = 7), BFU-E cells were significantly reduced (p < 0.001) whereas the reduction in CFU-GM cells was only of borderline significance (p = 0.037) compared with the age matched controls (n = 20). The CFU-GEMM cells remained unchanged. Furthermore, BFU-E and CFU-GM cells were reduced in a dose dependent fashion, with increasing PbB or PbU, respectively. In the subjects exposed to lead EPO was in the normal range and did not increase in the presence of anaemia induced by lead. No correlations existed between EPO and PbB, PbU, or progenitor cells. CONCLUSION: The data suggest new aspects of lead induced anaemia besides the currently acknowledged shortened life span of erythrocytes and inhibition of haemoglobin synthesis. Two additional mechanisms should be considered: the reduction of BFU-E cells, and inappropriate renal EPO production in the presence of severe exposure to lead, which would lead to an inadequate maturation of BFU-E cells. (+info)
Lead induced anaemia due to traditional Indian medicine: a case report.
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Lead intoxication in adults without occupational exposure is a rare and unexpected event. The case of a western European is reported who had severe anaemia after ingestion of several ayurvedic drugs, obtained during a trip to India. Laboratory findings showed high blood lead concentrations, an increased urinary lead concentration, and an increased urinary excretion of delta-aminolaevulinic acid. Also, slightly increased urinary concentrations of arsenic and silver were found. Physicians should be aware that with growing international travel and rising self medication with drugs from uncontrolled sources the risk of drug induced poisoning could increase in the future. (+info)
Clinical pallor is useful to detect severe anemia in populations where anemia is prevalent and severe.
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Clinical pallor is recommended as a simple way to detect severe anemia, but more data are needed on its accuracy and usefulness when assessed by nonphysicians in diverse settings. We measured hemoglobin and trained non-physician health workers to assess clinical pallor of the conjunctiva, palm and nail beds in five population samples in Nepal and Zanzibar, where severe anemia is common. In total, 5,760 individuals were examined, 3,072 of whom were anemic and 192 of whom had severe anemia (hemoglobin <70 g/L). The prevalence of pallor did not correspond to the prevalence of anemia or severe anemia in the groups studied. However, in all studies, pallor at each anatomical site was associated with a significantly lower hemoglobin concentration. The relative performance of different anatomical sites was not consistent among studies, and we recommend that multiple sites be assessed. Pallor at any of the three sites detected severe anemia with >84% specificity. However, the sensitivity varied from 81% in Nepalese postpartum women to 29% in Zanzibari preschoolers in 1996. Overall estimates for sensitivity and specificity were 50 and 92%, respectively. Although imperfect, use of pallor to screen and treat severe anemia by primary care providers is feasible and worthwhile where severe anemia is common. Usually, the majority of persons with severe anemia will be detected at practically no cost. Many people who are not severely anemic will also receive treatment, but the costs of this error are low compared to the benefits. (+info)
Pathophysiology and treatment of fetal anemia due to placental chorioangioma.
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Placental chorioangiomas occur in 1% of pregnancies. Large chorioangiomas may cause serious complications such as fetal anemia, hydrops and fetal death. In this case report, a pregnancy complicated by a large placental chorioangioma is described. Severe fetal anemia without the occurrence of hydrops fetalis was suspected using ultrasound and Doppler examinations. Successful intrauterine blood transfusion was performed, with an unusually large amount of blood needed to obtain an adequate rise in fetal hematocrit. Two weeks later, at 32 weeks, the infant was born in good condition. In pregnancies with large chorioangiomas, we advise regular ultrasound and Doppler examinations, with the aim of detecting fetal anemia before hydrops develops. When anemia is suspected, fetal blood sampling is indicated and intrauterine transfusion therapy may be beneficial to preserve fetal health until maturity is reached. (+info)
Nitric oxide, malaria, and anemia: inverse relationship between nitric oxide production and hemoglobin concentration in asymptomatic, malaria-exposed children.
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The cause of the anemia associated with chronic, intermittent, asymptomatic, low-level parasitemia in children in malaria-endemic endemic areas is not well understood. Nitric oxide (NO) decreases erythropoiesis, and it is likely an important mediator of anemia of chronic disease. Production of NO is decreased in acute uncomplicated and cerebral malaria, but it is increased in asymptomatic Tanzanian children (with or without parasitemia). We hypothesized that chronic overproduction of NO in these asymptomatic children contributes to the anemia associated with subclinical/subpatent malaria. In 44 fasting, asymptomatic, malaria-exposed, Tanzanian children, NO production (measured using fasting urine NOx excretion) was inversely associated with hemoglobin concentration (P = 0.03, controlling for age and gender). Using multiple linear regression, hemoglobin concentration was negatively associated with parasitemia (P = 0.005). After controlling for age and parasitemia, NO was no longer an independent predictor of anemia. One of the mechanisms of parasite-related anemia in such children may be through the adverse hematologic effects of parasite-induced NO production. (+info)