Assessment of cardiac index in anemic patients

STUDY OBJECTIVES: During isovolemic hemodilution, healthy individuals maintain oxygen consumption VO2 by identical increases in cardiac index (CI) and oxygen extraction ratio (O(2)ER). In critically ill patients, the relationship between CI and O(2)ER may be different. Patients with an altered cardiac function may have a decreased CI/O(2)ER ratio, whereas patients with sepsis may have an increased CI/O(2)ER ratio. We hypothesized that the analysis of the CI-O(2)ER relationship could help us to assess the adequacy of cardiac function in critically ill patients with anemia. DESIGN: Prospective, observational study. SETTING: Thirty-one-bed medicosurgical ICU of a university hospital. PATIENTS: Sixty patients equipped with arterial and Swan-Ganz catheters presenting with anemia, which was defined as a hemoglobin level < or = 10 g/dL in the absence of active bleeding. Patients were classified into those with compromised cardiac function (group 1; n = 40), and those with normal cardiac function (group 2; n = 20). Measurements and results: In addition to the pertinent clinical data, initial hemodynamic measurements, including pulmonary artery occlusion pressure (PAOP), CI, and O(2)ER, were collected in all patients at the onset of anemia. As anticipated, group 1 patients (n = 40) had lower CIs, higher O(2)ER levels, and lower CI/O(2)ER ratios than group 2 patients. However, there was no significant difference in PAOP values between the groups. The CI/O(2)ER ratio was < 10 in 27 of 40 group 1 patients but only in 4 of 20 group 2 patients. Of these latter four patients, three were found to be hypovolemic, and one patient with sepsis had severe myocardial depression. There was no statistically significant difference in PAOP in group 2 patients with or without hypovolemia ([mean +/- SD] 12.3+/-2.1 mm Hg) vs 13.7+/-4.3 mm Hg; p = 0.21). In group 1, survivors had a higher CI and CI/O(2)ER ratio than nonsurvivors. In group 2, however, such a relationship did not reach statistical significance. CONCLUSIONS: The relationship between CI and O(2)ER level can help interpret the CI in anemic patients. In anemic patients with no cardiac history, a low CI/O(2)ER ratio (< 10) suggests hypovolemia even when CI is not depressed.     

Serum iron and iron stores in non-anemic patients with fibromyalgia

The aim of the study was to assess iron serum levels and markers of iron stores in non-anemic fibromyalgia (FM) patients and to evaluate their impact on the prevalence and clinical manifestations of FM patients. Eighty-four patients with primary FM and 87 controls were investigated. Demographic and clinical data were collected from all participants. All patients completed the fibromyalgia impact questionnaire (FIQ). Patients evaluated the effect of the disease on their daily activity (DA) and judged the severity (DS) of the disease on a 0–10 scale. Venous blood was tested for serum iron, transferrin, ferritin, and soluble transferrin receptors (sTfR). Iron deficiency was defined if any of the following were present: serum iron <40 μg/dL, serum ferritin levels <10 ng/mL, or sTfR levels >28.1 nmol/L. Analysis at a cutoff level of serum ferritin levels ≤30 ng/mL and sTfR/ferritin ratio was also performed. Hemoglobin, iron, transferrin, sTfR, ferritin levels, and sTfR/ferritin ratios did not differ between the groups. The mean FIQ score was 57.13 ± 20.21 and the DA and DS scores were 6.79 ± 2.97 and 6.74 ± 3.09, respectively. No correlations were found between the parameters studied and the FIQ or its ten individual items. Thirty-eight controls (43.7%) and 23 FM patients (27.4%) had ferritin levels of ≤30 (p < 0.04). Within the FM group, lower levels were associated with lower total FIQ score and FIQ subscale scores. Patients with FM do not have reduced serum levels of iron or surrogate markers of iron stores. At present, there is no evidence to support iron supplementation in the treatment of FM.     

Detecting iron deficiency in anemic patients with concomitant medical problems

OBJECTIVE: To determine the sensitivity and specificity of mean corpuscular volume, transferrin saturation, total iron-binding capacity, and ferritin level in determining iron deficiency in a population of anemic veterans with a wide variety of general medical diagnoses. DESIGN: Retrospective chart review. SETTING: Hospitals of the Department of Veterans Affairs in Madison and Milwaukee, Wisconsin. PARTICIPANTS: One hundred one anemic veterans with any medical condition who underwent bone marrow aspiration and serum iron studies. MEASUREMENTS AND MAIN RESULTS: Using the presence or absence of bone marrow hemosiderin as the reference standard, the sensitivity and specificity of the following serum iron indicators were calculated: mean corpuscular volume, transferrin saturation, total iron-binding capacity, and ferritin level. Of these patients, 41 (40.6%) were categorized as iron deficient, with no stainable bone marrow hemosiderin. A serum ferritin level ≤ 100 μg/L provided the best sensitivity (64.9%) and specificity (96.1%) for evaluating iron stores in this patient population. When performed within 24 hours of bone marrow examination, a serum ferritin level ≤ 100 μg/L was 100% accurate in separating iron-deficient from iron-sufficient patients. None of the other serum iron indicators alone or in combination performed better than ferritin level alone. CONCLUSIONS: In a population of anemic veterans with a wide variety of concomitant medical problems, a serum ferritin level ≤ 100 μg/L was optimal for determining iron deficiency. This is higher than the ferritin level of ≤ 50 μg/L cited in standard textbooks as evidence of iron deficiency in patients with inflammation, infection, or malignancy. Received from the University of Wisconsin Department of Medicine, Section of Geriatrics and Gerontology, and the Department of Veterans Affairs Geriatric Research, Education, and Clinical Center, Madison, Wis. Dr. Carnes is a professor in the Department of Medicine and Director of Women’s Health at the William S. Middleton Veterans Hospital, and Dr. Kis was an internal medicine resident at the University of Wisconsin at the time this work was performed. This work was supported by the Madison Geriatric Research Education and Clinical Center (GRECC) and the University of Wisconsin Department of Medicine.     

Assessment of iron stores in children with transfusion siderosis by biomagnetic liver susceptometry

To investigate the applicability of noninvasive Superconducting Quantum Interference Device (SQUID) biomagnetic liver susceptometry and its limitations in thalassemic children, 23 patients with beta-thalassemia major and other iron loading anemias (age: 4-16 years) and 16 age-related normal children were studied. Liver iron concentrations ranged from 600 to 11,000 microg/g(liver) for thalassemic patients and from 60 to 340 microg/g(liver) for normal patients. Measuring the respective organ volumes by sonography, liver and spleen iron stores, accounting for 80% of total body iron stores, were estimated. Nonliver contributions from the lung or intestine to the measured SQUID signals in the small-sized patients were not observed. Moreover, livers in thalassemia were found to be enlarged by 18% per 1,000 microg/g (r = 0.75, P < 10(-3)). Serum ferritin values correlate significantly with iron stores (r = 0.64, P < 10(-3)), but predict iron stores only within large error intervals of 4,000 microg/g(liver). Analyzing the experimental data from biomagnetometry and from related transfusion and chelation treatment data within the framework of a two-compartment model, we were able to derive additional information on total body iron elimination and chelation therapy efficacy. The exponential decline of iron stores allows forecast of steady-state conditions of the final iron load for a particular transfusion and chelation therapy regimen.     

Hepatic iron stores and markers of iron overload in alcoholics and patients with idiopathic hemochromatosis

Liver iron concentrations were determined in 60 alcoholics with liver disease of varying severity, 15 patients with untreated idiopathic hemochromatosis, and 16 control subjects with biliary tract disease. Mean liver iron concentrations (g/100 mg dry weight) were significantly greater in the alcoholics (156.4±7.8 (sem);P<0.05) and in patients with idiopathic hemochromatosis (2094.5±230.7;P<0.01) than in control subjects (53.0±7.0). Liver iron concentrations of >140 g/100 mg were found in 17 alcoholics (29%) and in all 15 patients with idiopathic hemochromatosis. Liver iron concentrations >1000 g/100 mg were found in all patients with idiopathic hemochromatosis but in none of the alcoholics. In the alcoholics no relationship existed between liver iron concentrations and the amount of alcohol consumed daily, the length of the drinking history, the amount of beverage iron consumed daily, or the severity of the liver disease. Serum ferritin concentrations reflected iron stores in patients with hemochromatosis and in alcoholics with minimal liver disease. However, in alcoholics with significant liver disease serum ferritin concentrations did not reflect iron stores accurately, although with normal values iron overload is unlikely. Serum iron concentration and percentage saturation of total iron-binding capacity were of little value in assessing iron status in either alcoholics or patients with hemochromatosis. Measurement of the liver iron concentration clearly differentiates between alcoholics with significant siderosis and patients with idiopathic hemochromatosis.R. W. Chapman was Watson-Smith Fellow of the Royal College of Physicians of London.     

Red cell ferritin and iron stores in patients with chronic disease

Serum and red cell ferritin were determined in a heterogeneous group of 59 patients with chronic disease undergoing a bone marrow biopsy. There was very little correlation between serum and red cell ferritin (r = 0.53). Although serum ferritin increased in relation to increased bone marrow iron stores, only 1 out of 8 patients with absent marrow iron stores and none of 8 patients with reduced marrow iron stores had a decreased serum ferritin. In contrast, 6 of 8 patients with absent iron stores had a reduced red cell ferritin concentration. There was no significant difference between the mean red cell ferritin of the patients with reduced, normal and mild-moderately increased marrow iron stores (30, 26 and 34 ag/cell). Red cell ferritin was decreased in 78% of a group of 32 patients with a low mean cell volume. In the patients studied, red cell ferritin was a better indicator of absent iron stores than serum ferritin. However, red cell ferritin did not detect a reduction in the iron status until the marrow iron stores were completely depleted. Apparently, during normal erythropoiesis the primitive erythroblasts continue to take up iron irrespective of the amount of iron available in the stores.     

Body iron stores in patients subjected to surgery of the large bowel

Iron stores as estimated by serum ferritin concentration were studied in 40 patients subjected to colon surgery in reference to postoperative complications and restoration of iron stores, as well as to dietary and supplementary iron. The results showed that empty iron stores are common in patients subjected to colon surgery; 40 percent of the patients had a total loss before the operation. Preoperatively empty iron stores were associated (P<.01) with an increased risk of postoperative complications that were not explained by other nutritional parameters. Surgery of the colon did not affect serum ferritin concentration or iron stores acutely or long-term. Intake of dietary iron was determined by food recording for seven days in all patients and was compared to 40 controls. The preoperative hemorrhagia and lower daily intake of dietary iron (8±3 mg) in the patients than in the controls (14±4 mg) may explain the empty iron stores. However, patients with normal iron stores also had low amounts of dietary iron (9±3 mg). In 12 patients with empty iron stores the effects of ferrous sulfate (80 mg Fe⁺⁺) three times daily for six weeks were studied. The patients responded well to the therapy. It is concluded that preoperatively empty iron stores are common in patients subjected to colon surgery, and that this raises the risk of postoperative complications. Colon operations are not followed by acute or long-term changes in serum ferritin concentration or iron stores. The restoration of iron is achieved by oral iron therapy.     

Free erythrocyte protoporphyrin assay in the diagnosis of iron deficiency in the anemic aged subject. A prospective study of 103 anemic patients

We determined the relative value of the free erythrocyte protoporphyrin (FEP) assay compared to those of total iron-binding capacity (TIBC) and serum ferritin in the diagnosis of iron deficiency in a population of elderly anemic subjects. One hundred and three patients, 65 to 98 years old (mean +/- SD: 81.5 +/- 8.8), with hemoglobin levels of less than 110 milligrams (mean +/- SD: 97 +/- 12, range 53-109) were included in the study. In the patients with iron-deficiency anemia due solely to chronic bleeding, mean values for the three parameters were highly different from those in patients without chronic bleeding. In the patients with anemia due to an association of chronic bleeding and chronic inflammation, the mean FEP value was very significantly different (p less than 0.001) from that in the patients with chronic inflammation but without bleeding, whereas this was not the case for TIBC or serum ferritin. The sensitivity of FEP in the diagnosis of iron deficiency due to chronic bleeding in this population of anemic subjects was 60% (specificity 90%), compared to 13% (specificity 96%) for TIBC and 20% (specificity 100%) for serum ferritin. The FEP assay thus emerges as being highly suitable for the diagnosis of iron-deficiency anemia in the elderly subject, particularly when bone marrow is not examined.     

Liver iron stores in patients with secondary haemosiderosis under iron chelation therapy with deferoxamine or deferiprone

Summary. Total body iron stores including liver and spleen iron were assessed by non-invasive SQUID biomagnetometry. The liver iron concentration was measured in groups of patients with β-thalassaemia major or other post-transfusional siderosis under treatment with the oral iron chelator deferiprone (n = 19) and/or with parenteral deferoxamine (n = 33). An interquartile range for liver iron concentrations of 1680-4470μg/g liver was found in these patients. In both groups a poor correlation between liver iron and serum ferritin values was observed.
Repeated measurements of liver and spleen iron concentrations as well as determination of liver and spleen volume by sonography were performed in six patients under continuous deferiprone treatment for 3-15 months. In this group detailed information was obtained on the whole body iron store (5-36 g) and the iron excretion rates (14-34mg/d) for each patient. As indicated by decreasing liver iron concentrations, five out of six subjects showed a negative iron balance (2-13 mg/d). Conventional measurements of both serum ferritin and urine iron excretion gave fluctuating results, thus being only of limited use in the control of iron depletion therapy.
The non-invasive biomagnetic liver iron quantification is a precise and clinically verified technique which offers more direct information on the long-term efficacy of an iron depletion therapy than the hitherto used methods. This technique may be of use in the clinical evaluation of new oral iron chelators.     

Effects of alcohol consumption on indices of iron stores and of iron stores on alcohol intake markers

BACKGROUND: Alcohol increases body iron stores. Alcohol and iron may increase oxidative stress and the risk of alcohol-related liver disease. The relationship between low or "safe" levels of alcohol use and indices of body iron stores, and the factors that affect the alcohol-iron relationship, have not been fully characterized. Other aspects of the biological response to alcohol use have been reported to depend on iron status. METHODS: We have measured serum iron, transferrin, and ferritin as indices of iron stores in 3375 adult twin subjects recruited through the Australian Twin Registry. Information on alcohol use and dependence and smoking was obtained from questionnaires and interviews. RESULTS: Serum iron and ferritin increased progressively across classes of alcohol intake. The effects of beer consumption were greater than those of wine or spirits. Ferritin concentration was significantly higher in subjects who had ever been alcohol dependent. There was no evidence of interactions between HFE genotype or body mass index and alcohol. Alcohol intake-adjusted carbohydrate-deficient transferrin was increased in women in the lowest quartile of ferritin results, whereas adjusted gamma-glutamyltransferase, aspartate aminotransferase, and alanine aminotransferase values were increased in subjects with high ferritin. CONCLUSIONS: Alcohol intake at low level increases ferritin and, by inference, body iron stores. This may be either beneficial or harmful, depending on circumstances. The response of biological markers of alcohol intake can be affected by body iron stores; this has implications for test sensitivity and specificity and for variation in biological responses to alcohol use.     

Skin iron concentration: a simple, highly sensitive method for iron stores evaluation in thalassemia patients

Iron overload is a potentially fatal complication in thalassemia patients. Accurate assessment of body iron is of utmost importance for these patients. The available methods for iron stores evaluation have limitations. We assessed biochemically the skin iron concentration (SIC) and determined the relation between the hepatic and skin iron level in thalassemia major patients to develop a simple, sensitive, quantitative measure of the body iron stores. Thirty-one cases with thalassemia major were assessed for iron overload. Liver and skin biopsies were performed for the patients and skin biopsies were taken from the 31 controls. The biopsies were subjected to biochemical assay of iron and histologic sections were examined. The SIC of the studied cases was significantly higher than that of the control group with a mean of 2.705 +/- 1.14 and 0.275 +/- 0.13 mg/g dry skin weight, respectively, p < 0.001. There was significant correlation between the SIC and the liver iron concentration (LIC) (r = 0.43, p = 0.01). The amount of liver iron is equivalent to [(3.5 x SIC) + 12.9]. With the use of this equation, we could reliably estimate an LIC value as high as 21.2 mg/g dry liver weight with a standard error of 4.07. Biochemical assay of the skin iron concentration is a reliable quantitative indicator of the body iron stores in patients with thalassemia major.