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Severe anemia. Clinical observations in 100 patients with very low hemoglobin levels.

One hundred consecutive patients with hemoglobin concentration less than 3.5 g/dL (hematocrit reading, less than 10%) were admitted to the University of Baghdad Teaching Hospital, Iraq, during a 30-month period. Twenty-eight patients had aplastic anemia, 27 had leukemia or other hemopoietic malignancies, 16 had chronic renal failure, eight had iron-deficiency anemia, eight had hemolytic anemia, seven had thalassemia major, and six had other conditions. Twenty-three patients died within seven days of admission, mostly due to the underlying disease or complications thereof. Heart failure developed in ten patients, and five had retinal exudates and hemorrhages attributed to severe anemia. Arrhythmias and ECG abnormalities were noted in 20 of 68 patients. Blood transfusion was instituted in all but three patients, whose anemia was corrected with specific therapy without blood transfusion. The tolerance of the 100 patients to such severe anemia was remarkable.

Adolescent↗

Iron status and hemoglobin level in chronic renal insufficiency.

Much has been written on the important contribution of iron deficiency toward anemia and epoetin resistance among end-stage renal disease (ESRD) patients, but there are few studies of iron status among chronic renal insufficiency (CRI) subjects not yet requiring dialysis. The National Kidney Foundation-Kidney Disease Outcomes Quality Initiative (NKF-K/DOQI) Practice Guidelines recommend maintaining ferritin > or =100 ng/ml and transferrin saturation (TSAT) > or =20% to ensure adequate iron supply for erythropoiesis among patients with chronic kidney disease, whether or not they are dialysis-dependent. Analysis of the nationally representative data from the Third National Health and Nutrition Examination Survey (NHANES III 1988-1994) revealed that only a minority of anemic CRI subjects in the United States met these K/DOQI targets. For example, in the range of creatinine clearance (CrCl) 30 to 50 ml/min, less than one third of men with hemoglobin <12 g/dl and women with hemoglobin <11 g/dl had ferritin > or =100 ng/ml and TSAT > or =20%. In addition, TSAT levels above 20% were independently associated with higher hemoglobin levels. Such data raise the question whether the K/DOQI targets should be reevaluated. It is concluded that ferritin and TSAT targets derived from ESRD studies may not be applicable to subjects with CRI. Further studies are needed to guide optimization of iron status and hemoglobin level in the much larger CRI population.

Creatinine↗

Estimation of fetal hemoglobin levels in individual red cells via fluorescence image cytometry.

A method for estimating fetal hemoglobin (Hb F) levels in individual red blood cells was developed. Cell smears were prepared using a slide maker to ensure uniform thickness and were then stained with immunofluorescence. An antifading gel was applied to preserve a stable fluorescence. The total fluorescence intensities from the same number of red cells in different slide specimens correlated with their hemolysate Hb F levels, which were determined via column chromatography (R = 0.95). Hb F level in individual cells was estimated from fluorescence intensity and cell area, which were determined via image analysis techniques and the hemolysate Hb F level. Blood from a normal subject, a subject with hereditary persistence of fetal hemoglobin, and from sickle cell patients with varying Hb F levels was analyzed. Our analyses showed a wide distribution of Hb F among cells for the normal subject and a gaussian distribution with a peak at the hemolysate Hb F level for the subject with hereditary persistence of fetal hemoglobin. The Hb F distributions were unique to the patients with sickle cell disease. Because Hb F level in individual sickle cells is crucial to the inhibition of cell sickling, the unique hb F distribution may be important in determining the clinical course of this disease.

Anemia, Sickle Cell↗

Lack of influence of fetal hemoglobin levels or erythrocyte indices on the severity of sickle cell anemia.

Persons with sickle cell anemia who have elevated fetal hemoglobin or lowered erythrocyte mean corpuscular volume are reputed to have less severe clinical manifestations and a greater probability of survival. This study examines the relationship between seven clinical indicators of morbidity in sickle cell anemia and seven hematological parameters that were collected from 214 patients. Risks of sickle cell crisis, acute chest syndrome, hospital admissions, cerebrovascular accident, aseptic necrosis, meningitis/septicemia, and death were used as indicators of morbidity. The hematological parameters included percent fetal hemoglobin, absolute fetal hemoglobin, percent hemoglobin A2, hemoglobin concentration, packed cell volume, mean corpuscular volume, and mean corpuscular hemoglobin concentration. Statistical analyses of the data showed no relationship between the hematological parameters and six of the seven clinical indicators of the severity of sickle cell anemia. The only significant finding was an increased risk of stroke in those patients with lower levels of fetal hemoglobin. Therefore, with this exception, there is no predictable relationship between morbidity and mortality in sickle cell anemia and levels of fetal hemoglobin or erythrocyte indices. Thus, the general belief that there is an association between severity of sickle cell anemia and the levels of fetal hemoglobin has not been established.

Adolescent↗

Blood lead and hemoglobin levels in Andean children with chronic lead intoxication.

This study investigated blood lead (PbB) and hemoglobin (HbB) levels in 88 children (42 females and 46 males; ages: 2-15 years; mean age: 7.2) with chronic Pb exposure, living in a highly Pb-contaminated Andean village at above 2800 meters. The mean PbB level for 88 venous blood samples was 43.2 microg/dl (SD: 25.1; range: 6.2 - 128.2 microg/dl) measured by ICP-MS, and 42.0 microg/dl (SD: 26.0; range: 5.0 - 130.0 microg/dl) by GFAAS analysis. The mean PbB level for the 42 females was 41.0 microg/dl and for 46 males, 45.0 microg/dl. Multiple regression analysis showed a significant gender by age interaction (R2 = 0.099; F = 4.173, p = 0.044), indicating a relationship between age and PbB level for males, but not for females. Simple regression analysis showed a statistically significant positive correlation between PbB levels and age for males (r = 0.416, p = 0.004), but not for females (r = -0.042, p = .793). The measured mean HbB level for the 88 children was 12.6 g/dl (12.5 g/dl for females and 12.8 g/dl for males) and lower than expected for children living in the Ecuadorian Andes. The mean altitude-corrected HbB level was 10.9 g/dl (10.8 g/dl for females and 11.1 g/dl for males). A significant inverse correlation between PbB and HbB levels was observed for the group of 88 children (r = -0.292, p = 0.006). Multiple regression analyses indicated no significant age and gender interaction (R2 = 0.014; F = 0.025, p = 0.876) for HbB levels. In conclusion, the results of this investigation indicate that the children in this Pb-contaminated, high altitude study area had chronic elevated PbB levels, which increased with age for males, and probable Pb-induced anemia.

Adolescent↗

Effects of 5-aza-2'-deoxycytidine on fetal hemoglobin levels, red cell adhesion, and hematopoietic differentiation in patients with sickle cell disease.

Fetal hemoglobin (HbF) decreases polymerization of sickle hemoglobin (HbS) and improves outcomes in sickle cell disease (SSD). Therefore, a therapeutic goal in SSD is pharmacologic reactivation of HbF. Silencing of the gamma-globin (HbF) gene is associated with DNA methylation. The cytosine analog 5-aza-2'-deoxycytidine (decitabine) hypomethylates DNA by inhibiting DNA methyltransferase. We examined if subcutaneous decitabine could increase HbF levels and improve SSD pathophysiology without cytotoxicity. Eight symptomatic SSD patients resistant or intolerant of standard treatment with hydroxyurea received decitabine 0.2 mg/kg subcutaneously 1 to 3 times per week in 2 cycles of 6-week duration. Treatment decreased neutrophils and increased mean HbF (6.5% to 20.4%, P <.0001) and mean total hemoglobin (76 to 96 g/L [7.6 to 9.6 g/dL], P <.001). Features of vaso-occlusive crisis pathophysiology such as red cell adhesion, endothelial damage, and coagulation pathway activity significantly improved. gamma-Globin gene promoter methylation decreased, and platelets and the proportion of megakaryocytes and erythroid cells in the marrow increased without a decrease in marrow cellularity, consistent with a DNA hypomethylating, noncytotoxic mechanism of action. Weekly subcutaneous decitabine produces cumulative increases in HbF and total hemoglobin through a noncytotoxic mechanism of action. Chronic dosing and sustained increases in hemoglobin F and total hemoglobin levels may be possible. Further studies in SSD and thalassemia are indicated.

Adult↗

[Prognostic significance of hemoglobin levels in patients with heart failure].

INTRODUCTION AND OBJECTIVES: To evaluate the prognostic significance of hemoglobin (Hb) levels in terms of 1-year mortality and hospital admissions due to heart failure (HF) during the first year of follow-up after the first visit to an outpatient HF unit. PATIENTS AND METHOD: Survival status and HF-related hospital admission rate at 1 year were analyzed for 337 patients admitted between August 2001 and March 2003. Plasma Hb level was measured at the first visit to the unit. RESULTS: 28 patients (8%) died and there were 158 HF-related hospital admissions in 66 patients. Plasma Hb level correlated strongly with survival at 1 year, and was 13.0 +/- 1.7 g/dL in patients who were alive after this time, versus 11.7 +/- 1.6 g/dL (P < .001) in patients who died. Plasma Hb level also correlated with HF-related need for hospital admission, and was 13.1 +/- 1.7 g/dL in patients who were not hospitalized, versus 12.2 +/- 1.7 g/dL (P < .001) in patients with at least one hospital admission. In the multivariate logistic regression analysis plasma Hb level remained statistically associated both with 1-year survival and with the need for HF-related hospital admission. On the basis of a cutoff value for anemia of Hb < 12 g/dL, 30% of the patients had anemia. One-year mortality was 17% in patients with anemia and 5% in patients without anemia (P < .001). Among patients without anemia, 31% had at least one HF-related hospital admission, whereas only a 15% of the patients without anemia needed to be hospitalized for HF (P = .001). CONCLUSIONS: Plasma Hb levels correlated inversely with mortality and with HF-related hospital admissions at 1 year. The prevalence of anemia (Hb < 12 g/dL) in the population with HF studied here was high and had independent prognostic value.

Aged↗

The cellular basis for different fetal hemoglobin levels among sickle cell individuals with two, three, and four alpha-globin genes.

Fetal hemoglobin (HbF) levels vary widely among individuals with sickle cell anemia (SS). Previous studies have suggested that HbF levels in SS individuals with alpha-thalassemia (two or three functional alpha-globin genes) are lower than HbF levels in SS individuals with four normal alpha-globin genes. Using immunocytochemical techniques, we studied F cell production as measured by % F reticulocytes, the amount of HbF per F cell, and the preferential survival of F cells versus non-F cells in 51 subjects with four alpha genes, 32 subjects with three alpha genes, and 18 subjects with two alpha genes. Comparison between alpha-globin gene groups was performed for the total sample as well as for a subset of 82 individuals who had replicate samples and a further subset of 39 age-matched individuals. %HbF levels were 6.8, 4.9, and 4.5 percent for the total four-, three-, and two-alpha-globin-gene groups, respectively. The percentage of F reticulocytes, percentage HbF per F cell, and the enrichment ratio (% F cell/% F reticulocytes) did not change significantly with alpha-globin gene number. Moreover, no correlation existed between alpha-globin gene number and the absolute number of F cells in any group studied. However, there was a strong inverse correlation (r = -0.407, P = .0001) between non-F cell levels (1.7 +/- 2, 2.2 +/- 5, 3.0 +/- 1.0 X 10(12)/L) and decreasing alpha-globin gene number. These data suggest that falling HbF levels among SS individuals with lessened numbers of alpha-globin genes reflect prolonged survival of non-F cells and are not due to intrinsic differences in F cell production or in the amount of HbF per F cell. The improved survival of non-F cells in SS alpha-thalassemia is presumed to be due to the lower MCHC observed in such individuals.

Anemia, Sickle Cell↗

Physicians' practices in screening for the development of diabetic nephropathy and the use of glycosylated hemoglobin levels.

OBJECTIVE: To compare outpatient screening of diabetic patients for nephropathy and measurement of glycosylated hemoglobin (GHb) levels to published American Diabetes Association (ADA) guidelines. RESEARCH DESIGN AND METHODS: We reviewed charts from 157 diabetic patients followed for 27 months at the University of Washington's primary care clinics. The number of screening urinalyses, 24-h urine measurements, and GHb measurements were obtained. From these values, the frequency of screening tests, normalized by patient-year, could be compared with the ADA guidelines. RESULTS: Forty-two percent of the patients received at least one urinalysis, and 5% had 24-h urine measurements. There were 0.48 urinalyses and 0.05 24-h urine measurements per patient-year. Of 14 type I diabetes patients, 5 had a urinalysis and 1 received a 24-h urine measurement. At least one GHb was measured for 85% of patients, and there were 1.66 GHb measurements per patient-year. Only 29% of patients received GHb concentrations as recommended by ADA guidelines. CONCLUSIONS: Diabetic patients at this institution are not screened for nephropathy and do not receive GHb measurements according to the ADA guidelines. Because of recent advancements in the treatment of diabetic nephropathy and the results of the Diabetes Control and Complications Trial (DCCT), further efforts are needed for educating primary care physicians about standards of care of patients with diabetes.

Diabetic Nephropathies↗

Racial contrasts in hemoglobin levels and dietary patterns related to hematopoiesis in children: the Bogalusa Heart Study.

Racial differences in hemoglobin (Hgb) levels were explored in two groups of children at different maturational stages, the pre-adolescent (10-year-olds: Whites n = 160, Blacks n = 56,) and the adolescent (15-year-olds; Whites n = 60, Blacks n = 44). Mean Hgb levels were higher for Whites than Blacks in both age groups. When all the dietary components (i.e., iron, zinc, copper, folacin, ascorbic acid and vitamins B12, E and B6) were considered as a group, they accounted for 8.4 per cent of the Hgb variance in 10-year-olds and 10.1 per cent of variance in 15-year-olds. However, even after controlling for the variations in dietary patterns of the adolescents and pre-adolescents, race still accounted for a notable proportion of Hgb variance in both age groups (9.1 per cent in 10-year-olds and 7.0 per cent in 15-year-olds). Within each race, gender accounted for a greater percentage of the Hgb variance in the adolescents than in the pre-adolescents. Our results indicate that in all likelihood racial differences in Hgb levels during childhood exist independent of racial differences in intake of specific "blood building" nutrients and maturational changes.

Adolescent↗

The relationship between aminoaciduria and plasma hemoglobin levels.

Investigations in newborns, children and young adults have revealed an inverse proportion between aminoaciduria and plasma hemoglobin (Hb) levels. Values above normal were recorded for alanine, leucine, valine, phenylalanine and glutamic acid, correlating proportionally with their increased blood levels, and preceding or being concomitant with the decrease of plasma Hb, both during the first 20 months of life and in young adults. The return to near normal values of aminoaciduria occurred generally only after an early treatment with minerals, vitamins and trace elements (Supradyn), activators of the enzymes involved in the amino acid metabolism. After treatment, the Hb levels also became almost normal. An early re-equilibration of the amino acid metabolism can prevent the risk of developing, at the adult age, certain anemias and other diseases (rachitism, mental handicap, urinary infections, conjunctivitis, stomatitis, a.o.). The correlation factor was r = 0.964 and the differences between the data recorded in patients and in controls were statistically significant (p < 0.01).

Amino Acid Metabolism, Inborn Errors↗

Is there a generally valid, minimum acceptable hemoglobin level?

The different versions of autologous blood transfusion have rekindled interest in a generally valid 'minimum acceptable hemoglobin concentration' of patients around or below 10 g Hb/dl. The adequate Hb concentration capable of covering the oxygen demands of the body depends on several variables measurable at the bedside: oxygen consumption VO2, arterial oxygen tension paO2, body temperature, arterial and mixed venous pH, and cardiac output CO as the most important compensatory variable in anemia. Because of the strain imposed on the myocardium and the coronary circulation, anemia should not raise CO to more than twice the resting value, i.e. less than 10 l/min. Similarly, the mixed venous pO2, as an indicator of tissue oxygenation, should not fall below 35 mm Hg. With these two restrictions, we studied the relationships of the above-mentioned parameters in a computer-supported model. Under otherwise similar conditions, pvO2 falls with an increase in VO2, a decrease in paO2, a decrease in the temperature, an increase in pH, and a decrease in CO. A resting and slightly acidotic patient without other impediments of his cellular oxygen supply--e.g. the patient on chronic hemodialysis--tolerates a Hb level of 6-7 g/dl with a pvO2 barely exceeding 35 mm Hg and a CO approximately 50% above baseline. By contrast, the hypermetabolic and hypoxemic intensive care patient needs Hb levels in the low normal range, i.e. 12-13 g/dl, especially if he is also alkalotic. A generally valid 'minimum acceptable hemoglobin level' does not exist; the adequate Hb concentration is an individual characteristic needing careful attention.(ABSTRACT TRUNCATED AT 250 WORDS)

Anemia↗

Epoetin alfa 60,000 U once weekly followed by 120,000 U every 3 weeks increases and maintains hemoglobin levels in anemic cancer patients undergoing chemotherapy.

PURPOSE: Epoetin alfa administered s.c. three times weekly or once weekly increases hemoglobin (Hb) levels, decreases transfusion requirements, and improves quality of life in anemic cancer patients receiving chemotherapy. This study assessed the feasibility of using higher initial doses of once-weekly epoetin alfa followed by less frequent maintenance doses to increase and then maintain adequate Hb levels in this population. MATERIALS AND METHODS: In this open-label, nonrandomized, pilot study, anemic (baseline Hb < or = 11 g/dl) cancer patients undergoing chemotherapy received initial doses of epoetin alfa of 60,000 U s.c. once weekly to increase Hb levels by at least 2 g/dl, followed by 120,000 U s.c. every 3 weeks to maintain Hb levels. The maximum treatment duration was 24 weeks. RESULTS: The mean baseline Hb level was 10.1 +/- 0.8 g/dl (n = 20). Once-weekly dosing resulted in mean Hb level increases of 1.0 +/- 1.1 g/dl by week 4 and 2.9 +/- 1.9 g/dl by week 8; 86% and 79% of patients evaluable at week 8 and week 12, respectively, demonstrated increases of at least 2 g/dl (target Hb level of > or = 12 g/dl). Thirteen patients (65%) received at least one maintenance dose; the mean Hb level increased from 12.8 +/- 1.1 g/dl before starting maintenance therapy to 13.3 +/- 1.4 g/dl at the last maintenance week. Both dosage regimens were well tolerated. CONCLUSIONS: Once-weekly epoetin alfa at a dose of 60,000 U effectively increased Hb levels by week 8; 86% of patients achieved rises of at least 2 g/dl or Hb levels > or = 12 g/dl. Moreover, epoetin alfa at doses of 120,000 U every 3 weeks maintained or increased Hb levels. Results from this pilot study suggest that higher initial once-weekly dosing of epoetin alfa followed by less frequent maintenance dosing appears to be feasible for treating anemia in cancer patients undergoing chemotherapy. Further evaluation of these and other epoetin alfa dosage regimens is warranted.

Adult↗

Serum cholesterol and hemoglobin levels and calorie requirements in pregnant Nigerian women.

A study conducted on 50 healthy senior staff wives (socioeconomic group 1) and 63 healthy junior staff wives (socioeconomic group 2) attending the antenatal clinic at the University of Ife Health Center showed marked differences in the level of serum cholesterol and hemoglobin between the two groups. It was also found that women in group 2 took 6.8% of their total calorie requirements as fat and group 1 women took 12.0% of their total calorie requirements as fat.

Cholesterol↗

RAS and MTHFR gene polymorphisms in a healthy exercise-trained population: association with the MTHFR (TT) genotype and a lower hemoglobin level.

The aim of this study was to determine the frequencies of ACE (I/D), AGT (M235T), AT1R (A1166C) and MTHFR (C677T) polymorphisms in a well-defined (in regards to health and nutritional status and lifestyle) population of young, healthy, exercise-trained subjects (no. 100) from the Campania region of Southern Italy. We also investigated whether there was any correlation between these polymorphisms and biochemical, hematological and hemostatic parameters in this "low-risk" population. Gene polymorphisms were analyzed with the polymerase chain reaction and restriction enzyme analysis. Allele frequencies of the genotypes examined were in Hardy-Weinberg equilibrium and agree with those reported in the Italian population. No associations were found between ACE, AGT, AT1R gene polymorphisms and anthropometric, clinical and laboratory parameters. However, the MTHFR (C677T) polymorphism was significantly associated with lower hemoglobin plasma levels in TT vs. CC + CT females (p < 0.016). This report is the first to describe the frequencies of RAS and MTHFR gene polymorphisms in young, exercise-trained volunteers from Campania and to identify an association between the MTHFR gene polymorphisms and lower hemoglobin plasma levels in young healthy females.

Adult↗

The influence of l-carnitine supplementation on hematocrit and hemoglobin levels in patients with end stage renal failure on CAPD.

The influence of L-carnitine supplementation on hematocrit (Hct) and hemoglobin (Hb) levels, in patients suffering from end stage renal disease (ESRD) on maintenance hemodialysis, are well known from several studies. The data concerning the serum levels of carnitine, in patients with ESRD on continuous ambulatory peritoneal dialysis (CAPD) are contradictory, but most of them support that they are rather normal. In this study the effect of L-carnitine supplementation on Hct, and Hb levels were investigated in patients suffering from ESRD on CAPD. In the study 12 patients were included (5F, 7M), aged from 39 to 92 years old (median 65.5 years), who were on CAPD for more than 6 months (from 6 to 15 months, mean +/- SD = 8.6 +/- 3.6), with normal serum ferrum and ferritin levels at the beginning of the study. Two grams of L-carnitine/ day per os (Superamin, Vianex Hellas), were administered in all the patients and the serum ferrum levels were tried to be kept stable, by exogenous ferrum administration, during the study period. If the Hct levels were more than 36% per month the erythropoietin (rHuEpo) dose of the patient was decreased monthly at the half dose/week. The changes of Hct, Hb, ferrum and ferritin levels, as well as the Indice de Rigidite (IR) of the erythrocytes were recorded, before and after the first, second and third month of the study period. Finally, the rHuEpo dose/ patient was registered monthly before and during the study. During the observations, Hct (35.4 +/- 3.3 vs. 38.1 +/- 3.4, ANOVA, p < 0.03) and Hb levels (11.0 +/- 1.1 vs. 11.9 +/- 1, ANOVA, p < 0.01), were significantly increased. On the other hand, rHuEpo dose necessity/patient/week was decreased significantly (3,833 +/- 3326 vs. 1,292 +/- 1,712, ANOVA, p < 0.01), in order to succeed the target Hct level. Furthermore, red blood cells IR also appeared to have a significant decrease (16.6 +/- 7.4 vs. 13.0 +/- 3.9, paired t-test, p < 0.03). Finally, the ferrum and ferritin levels were stable during the study period. It was concluded, that in patients on, CAPD the per os L-carnitine supplementation decreased, the red blood cells IR which contributes to the: (a) Increase of Hct and Hb levels and (b) decrease of the patients rHuEpo dose/week.

Adult↗

Longitudinal trends of hemoglobin levels in a Japanese population--RERF's Adult Health Study subjects.

Conflicting results have been reported on the long-term relationship between hemoglobin (Hb) level and age. We analyzed that relationship over a 40-yr period in a Japanese population, adjusting for the effects of sex, birth cohort, smoking, and anemia-associated diseases. We used Hb levels measured biennially between 1958 and 1998 for 4858 Adult Health Study subjects of the Radiation Effects Research Foundation. Using the mixed-effects model, we showed that the aging Hb profile varied by sex (P < 0.001) and birth cohort (P < 0.001). Male Hb levels peaked in the third and fourth decades and then decreased while female Hb levels dipped slightly in the third decade, peaked in the sixth and seventh, and then decreased. Levels were higher in younger cohorts. The rate of Hb decline after the sixth decade of life was greater for subjects with anemia-associated diseases (P = 0.002). The annual rate of decline between 70 and 80 yr of age for disease-free men ranged from 0.083 to 0.042 g/dL and for disease-free women from 0.049 to 0.036 g/dL. Levels were higher for ever-smokers (P < 0.001), more so for women than men. A decreasing trend in Hb concentration with advancing age was detected for elderly men and women after controlling for anemia-associated diseases, suggesting that anemia in the elderly is due not only to disease but also to aging. Cohort and smoking effects on Hb levels were also observed.

Adolescent↗