Serum ferritin and free erythrocyte protoporphyrin in rheumatoid arthritis

Summary In this prospective study 20 newly diagnosed patients with definite or classical rheumatoid arthritis were followed with serial measurements of serum ferritin and erythrocyte-free protoporphyrin at the beginning of the trial and at 3 and 6 months. The values were correlated with clinical disease activity ad with various laboratory parameters. It was shown that free erythrocyte protoporphyrin has a constant negative correlation with erythrocyte haemoglobin concentration independent of disease activity, while serum ferritin behaves like an acute phase protein. Initial serum ferritin or free erythrocyte protoporphyrin values or their early changes appeared to have no prognostic value as evaluated by the development of new erosions or by the response of the patient to the therapy.     

Clinical significance of serum iron and ferritin in patients with colorectal cancer

To clarify the significance of serum iron and ferritin as indicators of iron loss caused by continuous bleeding, and, thus, to determine their value as markers of colorectal cancer, values for the two were compared in male patients with early and advanced colorectal cancer and age-matched male controls. The mean value of serum iron levels in patients with advanced colorectal cancer was significantly decreased compared with values in patients with early colorectal cancer and controls, 50.5 ± 38.6g/dl vs 93.0 ± 32.1 g/dl and 107.1 ± 32.9g/dl, respectively (p < 0.001).=" the=" mean=" value=" of=" serum=" ferritin=" levels=" in=" patients=" with=" early=" and=" advanced=" colorectal=" cancer=" was=" also=" significantly=" decreased=" compared=" with=" controls,=" 80.5=" ±=" 35.0ng/ml=" (p=">< 0.01)=" and=" 48.8=" ±=" 72.8=" ng/ml=" (p=">< 0.001),=" respectively,=" vs=" 117.1=" ±=" 46.8=" ng/ml.=" however,=" there=" was=" no=" significant=" difference=" between=" mean=" serum=" iron=" levels=" in=" patients=" with=" early=" colorectal=" cancer=" and=" controls.=" eighteen=" (78.3%)=" of=" the=" 23=" patients=" with=" advanced=" colorectal=" cancer=" and=" 3=" (16.7%)=" of=" the=" 18=" patients=" with=" early=" colorectal=" cancer=" had=" serum=" iron=" levels=" below=">g/dl and serum ferritin levels below 60ng/ml. Levels of both serum iron and ferritin, without clinically evident anemia, are useful indicators of advanced colorectal cancer.     

The role of serum ferritin in the diagnosis of iron deficiency anaemia in patients with liver cirrhosis

Intragumtornchai T, Rojnukkarin P, Swasdikul D, Israsena S (Division of Haematology, and Division of Gastroenterology, Department of Medicine, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand). The role of serum ferritin in the diagnosis of iron deficiency anaemia in patients with liver cirrhosis. J Intern Med 1998; 243 : 233–41.

Objectives

.To determine the diagnostic values of serum ferritin and other conventional laboratory tests in the diagnosis of iron deficiency anaemia in patients with liver cirrhosis.

Design

.Cross-sectional study for diagnostic tests.

Setting

.University hospital.

Subjects

.Seventy-two consecutive patients with liver cirrhosis in whom the haemoglobin level was less than 13.0 g dL^?1 for men and 12.0 g dL^?1 for women. The diagnosis of liver cirrhosis was based on characteristic clinical and hepatic ultrasonographic findings.

Main outcome measures

.By using absence of bone marrow iron as the standard criterion, the diagnostic powers of mean corpuscular volume, transferrin saturation, serum ferritin and the presence of hypochromic red cells in the diagnosis of iron deficiency were compared by analysing the likelihood ratios, the area under the receiver operating curves (ROC) and the stepwise logistic regression associated with each test.

Results.<

> Twenty-nine patients (40.3%) demonstrated no stainable iron in the bone marrow. The likelihood ratios, the area under the ROC and the stepwise logistic regression indicated that serum ferritin was the most powerful test predictive of iron deficiency. Other tests added little further diagnostic values. The likelihood ratios associated with the serum ferritin levels were as follows: <50 μg L^?1, 22.3; 51–200 μg L^?1, 1.5–1.8; 201–400 μg L^?1, 1.0; > 400 μg L^?1, <1. These results indicate that serum ferritin level <50 μg L^?1 depict a very high probability of iron deficiency anaemia (0.83–0.99) irrespective of the patient's pre-test probability.

Conclusion

.Serum ferritin is the most powerful non-invasive test for the diagnosis of iron deficiency anaemia in patients with liver cirrhosis. It should be the primary test of choice in patients suspected of having the disease. When the level was less than 50 μg L^?1, iron supplement may be prescribed without necessitating bone marrow aspiration.

     

Small-dose iron tolerance test and body iron content in normal subjects

Abstract: The small-dose iron tolerance test (SD-ITT) was performed in 37 healthy subjects (20 females and 17 males). The area under the curve (AUC) of serum iron variations after the test dose (10 mg of iron as iron sulphate) was corrected by the expected plasma iron disappearance rate, the expected subject's plasma volume and the measured spontaneous time-dependent serum iron variations, and was used as a summary measure of the outcome, Q-ITT. Q-ITT correlated strictly with the maximum serum iron increase (SImax). Q-ITT gave positive (greater than zero) values in only 14 out of the 37 subjects (11 females and 3 males). Serum ferritin proved to be the best discriminating parameter between positive and non-positive subjects, and was inversely correlated with Q-ITT in the positive ones. In 2 male subjects, aged 43 and 34 years, SD-ITT proved to be highly sensitive to the progressive decrease of mobilzable body iron content during repeated venesections. In these patients the threshold for a positive test result was obtained at values lower than 1050 and 950 mg of body iron content, respectively. The threshold-dependent sensitivity, simplicity, and repeatability of this method favor its becoming a useful technique for studying the up-regulation of iron absorption in normal subjects and in pathological conditions.     

Serum iron and ferritin levels in patients with colorectal cancer in relation to the size, site, and disease stage of cancer

We investigated blood loss from colorectal cancer in 92 men seen between January 1990 and June 1997, in relation to the size and site of the tumor, Dukes stage, pathologic type of cancer, and serum carcinoembryonic antigen (CEA) positivity. We used indirect methods, measuring serum hemoglobin, iron, and ferritin concentrations. The means of these three concentrations were significantly lower in patients with a tumor >3 cm than in those with a tumor ≤3 cm in largest diameter. The means of the three values were lower in patients with proximal colon cancer than in those with distal colon cancer, but only the difference in serum hemoglobin concentration was significant. Cancers of the ulcerative type were found more often in the proximal colon. The proportion of patients with Dukes stage C or D was not different between those with proximal colon cancer and those with distal colon cancer. There was a positive correlation between tumor size and Dukes stage. There were no differences in serum hemoglobin, iron, and ferritin concentrations with respect to the pathologic type of cancer and CEA positivity. These findings show that blood loss from colorectal cancer is closely related to the size and site of the tumor. (Received: June 12, 1998; accepted: Oct. 23, 1998)     

The ratio of serum transferrin receptor and serum ferritin in the diagnosis of iron status

Laboratory tests used in the diagnosis of iron status lack specificity in defining iron deficiency anaemia (IDA) and anaemia of inflammation (AI). The serum transferrin receptor (sTfR) may provide more information in this regard. The iron status of 561 pre-school children was determined and classified using the conventional measurements. The value of the concentration of sTfR, the ratio of sTfR (microg/ml) to LogSF (microg/l) (TfR-Index), and the Log of the ratio of sTfR (microg/l) to SF (microg/l)--(LogTfR:Fer ratio), in the classification of the iron status were determined by comparing their distributions across the classification of iron status. Although there were significant differences in sTfR and TfR-Index across the categories of iron status, there was considerable overlap. All subjects with iron deficiency had LogTfR:Fer ratio > 2.55, whereas in all subjects classified as AI it was < 2.55, thus clearly separating the two. The LogTfR:Fer ratio was not able to exclude IDA in the presence of inflammation. However, in cases of combined IDA and AI the LogTfR:Fer ratio was < 2.55 but increased to > 2.55 after resolution of the inflammation. This novel method of calculating the LogTfR:Fer ratio may provide a more precise classification of the iron status of children.     

Response of iron overload to deferasirox in rare transfusion-dependent anaemias: equivalent effects on serum ferritin and labile plasma iron for haemolytic or production anaemias

Objectives: It is widely assumed that, at matched transfusional iron‐loading rates, responses to chelation therapy are similar, irrespective of the underlying condition. However, data are limited for rare transfusion‐dependent anaemias, and it remains to be elucidated if response differs, depending on whether the anaemia has a primary haemolytic or production mechanism. Methods: The efficacy and safety of deferasirox (Exjade^®) in rare transfusion‐dependent anaemias were evaluated over 1 yr, with change in serum ferritin as the primary efficacy endpoint. Initial deferasirox doses were 10–30 mg/kg/d, depending on transfusion requirements; 34 patients had production anaemias, and 23 had haemolytic anaemias. Results: Patients with production anaemias or haemolytic anaemias had comparable transfusional iron‐loading rates (0.31 vs. 0.30 mL red blood cells/kg/d), mean deferasirox dosing (19.3 vs. 19.0 mg/kg/d) and baseline median serum ferritin (2926 vs. 2682 ng/mL). Baseline labile plasma iron (LPI) levels correlated significantly with the transfusional iron‐loading rates and with serum ferritin levels in both cohorts. Reductions in median serum ferritin levels were initially faster in the production than the haemolytic anaemias, but at 1 yr, similar significant reductions of 940 and 617 ng/mL were attained, respectively (?26.0% overall). Mean LPI decreased significantly in patients with production (P < 0.0001) and haemolytic (P = 0.037) anaemias after the first dose and was maintained at normal mean levels (<0.4 μm ) subsequently. The most common drug‐related, investigator‐assessed adverse events were diarrhoea (n = 16) and nausea (n = 12). Conclusions: At matched transfusional iron‐loading rates, the responses of rare transfusion‐dependent anaemias to deferasirox are similar at 1 yr, irrespective of the underlying pathogenic mechanism.     

Body iron stores,dietary iron intake and coronary heart disease mortality

Abstract. Objectives. To assess whether increased body iron stores and dietary iron intake are associated with an increased risk of coronary heart disease mortality. Design. A prospective population study with a mean mortality follow-up time of 14 years. Setting. Participants attending a health screening examination carried out in several localities in Finland. Subjects. All 6086 men and 6102 women aged from 45 to 64 years at the baseline examination without known heart disease, who had had serum iron and total iron binding capacity (TIBC) assessed. In a random fifth of these people, dietary iron intake was assessed by a dietary history. Interventions. The study was observational without any interventions. Main outcome measures. Mortality from coronary heart disease. Results. Altogether, 739 of the men and 245 of the women died from coronary heart disease. No relationship between TIBC and coronary mortality was observed in the men; in the women, an inverse although not significant association was found. Transferrin saturation was inversely but not significantly associated with coronary mortality in men; in women, the relationship was U-formed with a higher mortality at both the lower and higher ends of the distribution. Adjustment for other risk factors did not alter the results. No association was found with dietary iron intake and coronary mortality. Conclusions. The results do not corroborate earlier findings that excess body iron stores and increased iron intake are associated with an elevated risk of coronary heart disease.     

Combined use of erythrocyte zinc protoporphyrin and mean corpuscular volume in differentiation of thalassemia from iron deficiency anemia

Abstract: In a retrospective study the diagnostic value of erythrocyte zinc protoporphyrin (ZPP) measurement as a means of distinguishing iron deficiency anemia from thalassemia syndromes in patients with microcytosis was explored. ZPP values were increased in all patients with iron deficiency and in part of the patients with thalassemia. The combined measurement of erythrocyte mean corpuscular volume (MCV) and ZPP resulted in a correct classification of patients with iron deficiency and with thalassemia in more than 95%. The predictive value of this method is better than the results obtained by using formulae derived from red cell indices. In population screening programs for thalassemia syndromes, in which MCV determination is used as the initial test, the ZPP test is recommended as a second test, in order to discriminate between patients with microcytosis due to iron deficiency and patients with microcytosis due to thalassemia syndromes.     

血清铁、铁蛋白和脂肪肝关系的研究

目的　研究血清铁、血清铁蛋白与酒精性、非酒精性脂肪肝的关系。方法　采用 1秒钟快速肝穿刺 ,对 97例脂肪肝患者取肝组织标本 ,行HE和铁染色 ,分别用原子吸收光谱法和放射免疫法检测患者的血清铁和血清铁蛋白。结果　中重度酒精性脂肪肝 (AFL)血清铁、血清铁蛋白测定值 [(2 0 .9± 9.3) μmol/L ,(2 17.6± 71.8)ng/ml;(2 9.1± 6 .5 ) μmol/L ,(2 84 .7± 77.9)ng/ml]与对照组 [(10 .5± 5 .7) μmol/L ,(14 3.3± 71.9)ng/ml]比较明显升高 (P <0 .0 1)。重度非酒精性脂肪肝 (NAFL)的血清铁和血清铁蛋白 [(2 1.5± 11.1) μmol/L ,(199.3±72 .1)ng/ml]和对照组 [(10 .5± 5 .7) μmol/L ,(14 3.3± 71.9)ng/ml]比较亦显著升高 (P <0 .0 1) ,而且AFL多出现肝细胞灶性坏死 (6 7% )和肝铁过载(87% )。结论　重度NAFL及中重度AFL多出现血清铁和铁蛋白增高 ,AFL多合并肝铁过载 ,血清铁、铁蛋白可以作为肝铁过载的重要指标。     

Non-invasive liver iron quantification by SQUID-biosusceptometry and serum ferritin iron as new diagnostic parameters in hereditary hemochromatosis

In the HFE-gene era, precise diagnostic parameters remain important to characterize individual iron stores, because the indication for therapy and prognosis are mainly related to the extent of iron loading. The frequently used serum ferritin interferes with non-iron related factors such as inflammation and may produce falsely positive values. We used a SQUID-biosusceptometer in a large series of patients (n = 679) to measure liver iron concentration in the differential diagnosis and therapy control of hereditary hemochromatosis (SQUID = superconducting quantum interference device). This truly non-invasive technique is sensitive, reliable, fast (online results), and also cost-effective when compared to invasive liver biopsy. Recently, ferritin iron content was propagated as a better parameter than ferritin protein. However, we found a poor correlation between ferritin iron and individual liver iron concentrations in patients with iron overload. Ferritin iron saturation varied in a range between 3 and 10%, independent from liver iron concentration. No differences were found between patients with hemochromatosis and secondary iron overload disease. Only patients with liver cell damage had increased ferritin iron saturations. In conclusion the diagnostic values of serum ferritin protein and iron to assess iron overload are limited.     

Defining serum ferritin thresholds to predict clinically relevant liver iron concentrations for guiding deferasirox therapy when MRI is unavailable in patients with non‐transfusion‐dependent thalassaemia

Liver iron concentration (LIC) assessment by magnetic resonance imaging (MRI) remains the gold standard to diagnose iron overload and guide iron chelation therapy in patients with non‐transfusion‐dependent thalassaemia (NTDT). However, limited access to MRI technology and expertise worldwide makes it practical to also use serum ferritin assessments. The THALASSA (assessment of Exjade^® in non‐transfusion‐dependent THALASSemiA patients) study assessed the efficacy and safety of deferasirox in iron‐overloaded NTDT patients and provided a large data set to allow exploration of the relationship between LIC and serum ferritin. Using data from screened patients and those treated with deferasirox for up to 2 years, we identified clinically relevant serum ferritin thresholds (for when MRI is unavailable) for the initiation of chelation therapy (>800 μg/l), as well as thresholds to guide chelator dose interruption (<300 μg/l) and dose escalation (>2000 μg/l). (clinicaltrials.gov identifier: NCT00873041).     

Reticulocyte haemoglobin content vs. soluble transferrin receptor and ferritin index in iron deficiency anaemia accompanied with inflammation

Ferritin concentration, as a parameter of iron status that is commonly used in the diagnosis of iron deficiency anaemia (IDA), often has limited values if the iron deficiency is accompanied by inflammatory disease. This study evaluated the value of reticulocyte haemoglobin content (CHr) and soluble transferrin receptor-ferritin index (sTfR/F) in the diagnosis of IDA and differential diagnosis of IDA and anaemia of chronic disease. The study included 66 nonanaemic individuals as controls, 86 patients with IDA divided into noninflammatory and inflammatory subgroups, and 32 patients with anaemia of chronic disease. Blood count, iron, transferrin saturation, total iron binding capacity, ferritin, C-reactive protein, sTfR and CHr were determined. Receiver operator characteristic curve analysis showed very high discriminating power for CHr, soluble transferrin receptor (sTfR) and sTfR/F in the diagnosis of IDA. In patients with anaemia of chronic disease these parameters showed no significant difference from the control. CHr and sTfR enabled recognition of iron deficiency and were not affected by acute phase reaction. They are sensitive markers of body iron status with additional value to conventional tests for the detection of iron deficiency.     

Determinants of iron status and bilirubin levels in congenital dyserythropoietic anaemia type I

Seven untransfused patients with congenital dyserythropoietic anaemia type I were investigated to assess the determinants of both iron overload and serum bilirubin levels. The serum ferritin concentration was increased in all patients and non-transferrin-bound iron (NTBI) was increased in all but one patient. None of the patients showed the C282Y mutation in the hereditary haemochromatosis gene, HFE. One patient was homozygous for the H63D mutation in this gene. The data indicated that differences in the extent of iron overload were not mediated by co-inheritance of the C282Y mutation in the HFE gene but could largely be explained by differences in the severity of anaemia and ineffective erythropoiesis, and in the age of the patient. In one patient an unusually high plasma bilirubin level was associated with the variant A[TA]7TAA configuration in the TATA box of the uridine diphosphate glucuronosyltransferase (UGT-1A) gene promoter, the mutation found in most patients with mild Gilbert's syndrome.