Serum ferritin, blood donation, iron stores and haemochromatosis

Summary. Serum iron and ferritin concentrations were measured in 1,532 regular blood donors from South Wales who were undergoing HLA typing prior to registration on the British Bone Marrow and Platelet Donor Panel. Serum transferrin concentrations were determined for donors with serum iron concentrations > 24 µmol/1. There were 25 donors with transferrin saturations > 50% and 11 with transferrin saturations > 60%. There were five donors with serum ferritin concentrations > 200 µg/1 (women) or > 300 µg/1 (men). Two of the male donors had transferrin saturations > 50% and serum ferritin >300 µg/1 on repeat blood samples and are being treated by venesection. Donors with HLA-A3 did not differ from those without A3 in serum iron or ferritin concentrations. Even in the group of donors who were apparently homozygous for A3 there were neither abnormal serum iron nor ferritin concentrations.
Although it is well established that measurements of transferrin saturation are required to detect homozygous haemochromatosis ( HFE ) in its earlier stages, the number of 'false-positive' results is likely to be unacceptably high for screening blood donors. Serum ferritin assays should identify donors with HFE and iron overload before the onset of liver damage. With two million regular donors and 300,000 new donors each year, a significant proportion of the U.K. population will be screened within 10 years. The assay of serum ferritin identifies donors with low levels of storage iron who are at risk of developing iron-deficiency anaemia. Furthermore, donation frequency may be increased for those donors with higher ferritin concentrations when blood supplies are low.     

育龄期女性缺铁性贫血患者血清铁调素和erythroferrone水平的变化

目的:检测育龄期女性缺铁性贫血(Iron deficiency anemia,IDA)患者血清铁调素和erythroferrone(ERFE)含量,并探讨其与铁代谢各参数的相关性.方法:选取住院育龄期女性缺铁性贫血患者35例,年龄相匹配的健康女性对照人群30例.采用全自动电化学发光仪检测血清铁蛋白水平,全自动生化仪测定...     

Relationships of serum ferritin, transferrin saturation, and HFE mutations and self-reported diabetes in the Hemochromatosis and Iron Overload Screening (HEIRS) study

OBJECTIVE: We evaluated the associations of self-reported diabetes with serum ferritin concentration, transferrin saturation (TfSat), and HFE C282Y and H63D mutations in six racial/ethnic groups recruited at five field centers in the Hemochromatosis and Iron Overload Screening (HEIRS) study. RESEARCH DESIGN AND METHODS: Analyses were conducted on 97,470 participants. Participants who reported a previous diagnosis of diabetes and/or hemochromatosis or iron overload were compared with participants who did not report a previous diagnosis. RESULTS: The overall prevalence of diabetes was 13.8%; the highest prevalence was in Pacific Islanders (20.1%). Of all participants with diabetes, 2.0% reported that they also had hemochromatosis or iron overload. The mean serum ferritin concentration was significantly greater in women with diabetes in all racial/ethnic groups and in Native-American men with diabetes than in those without diabetes. The mean serum ferritin concentration was significantly lower in Asian men with diabetes than in those without diabetes. Mean TfSat was lower in participants with diabetes from all racial/ethnic groups except Native-American women than in those without diabetes. There was no significant association of diabetes with HFE genotype. The mean serum ferritin concentration was greater (P < 0.0001) in women with diabetes than in those without diabetes for HFE genotypes except C282Y/C282Y and C282Y/H63D. Log serum ferritin concentration was significantly associated with diabetes in a logistic regression analysis after adjusting for age, sex, racial/ethnic group, HFE genotype, and field center. CONCLUSIONS: Serum ferritin concentration is associated with diabetes, even at levels below those typically associated with hemochromatosis or iron overload.     

Soluble transferrin receptor and soluble transferrin receptor-ferritin index for evaluation of the iron status in elderly patients

We aimed to evaluate the diagnostic values of soluble transferrin receptor (sTfR) concentration, transferrin-ferritin index (soluble transferrin receptor concentration/log ferritin), ferritin levels and other related parameters in geriatric patients with anemia of chronic disease (ACD) and iron deficiency (IDA). Forty-four elderly subjects (median age 73 [63-94]) and twenty healthy subjects (median age 49 [44-56]) were enrolled into this study, divided into four groups: twenty middle aged healthy subjects (group A), fifteen elderly patients with IDA (group B), fourteen elderly patients with ACD (group C) and fifteen nonanemic geriatric subjects (group D). Hemoglobin, mean corpuscular volume, serum iron concentration and transferrin saturation levels of the patients in IDA group were found significantly lower than those in both non-anemic group and healthy subjects. Serum sTfR concentrations of the patients in IDA group were significantly higher than those in non-anemic geriatric group, ACD group and healthy subjects. Transferrin-ferritin index of the patients with IDA was significantly higher than that in non-anemic geriatric and ACD group. Serum ferritin levels of the patients in IDA group did not show any differences when compared with the other groups. Serum ferritin was highly specific for IDA (95%) when compared with ACD, although its sensitivity was low (38%). STfR values were negatively correlated with both transferrin and ferritin levels (p = 0.042 r = -0.40; and p = 0.034 r = -0.41, respectively). In conclusion, serum soluble transferrin receptor and transferrin-ferritin index may be used together with serum ferritin to distinguish the iron deficiency state in the elderly.     

慢性肾脏病晚期肾性贫血患者可溶性转铁蛋白受体水平变化及意义

目的探讨血清可溶性转铁蛋白受体（solubletransferrinreceptor,s—TfR）水平在慢性肾脏病（chronickidneydisease,CKD）晚期肾性贫血患者中的临床意义。方法CKD4～5期患者60例,测定血清s—TfR、铁蛋白、铁、转铁蛋白等指标水平,计算肾小球滤过率和转铁蛋白饱和度,比较CKD4期与5期患者铁状态评估指标的差异,分析s—TfR与铁蛋白及转铁蛋白饱和度的相关性。结果CKD4期患者铁蛋白、转铁蛋白饱和度明显高于5期患者,而s—TfR明显低于5期患者（P均〈0．05）;s—TfR与铁蛋白及转铁蛋白饱和度呈负相关（r=-0．398,P〈0．05;r=-0．817,P〈0．01）。结论CKD5期患者铁缺乏状态较CKD4期患者严重,s—TfR可作为判断CKD晚期肾性贫血患者体内铁缺乏的指标之     

The influence of iron,vitamin B(12), and folate levels on soluble transferrin receptor concentration in pregnant women

BACKGROUND: Soluble transferrin receptor (sTfR) concentration is high in iron deficiency and in conditions of increased erythropoiesis. In developing countries like Brazil, pregnant women usually have concurrent iron, vitamin B(12), and folate deficiencies. This study investigated the relationship between serum sTfR concentration and iron, vitamin B(12), and folate status in pregnant women. METHODS: The concentration of the sTfR, hematocrit (Hct), hemoglobin (Hb), red blood cell (RBC) and white blood cell (WBC) counts, serum iron (SI), total iron-binding capacity (TIBC), transferrin saturation, serum ferritin, zinc protoporphyrin (ZPP), vitamin B(12), and serum and RBC folate were determined in 40 healthy pregnant women who delivered term babies. RESULTS: sTfR concentration was significantly higher when the women had iron deficiency (serum ferritin <10 microg/l, p<0.01), but there was no significant difference in sTfR concentration according to vitamin B(12), serum, and RBC folate concentrations. Women who had serum ferritin <10 microg/l also had lower vitamin B(12) values (p<0.01). There was no significant correlation between vitamin B(12) and serum folate with sTfR concentration. According to a regression analysis, sTfR concentration was associated with serum iron, serum ferritin, RBC count, and hemoglobin concentration. CONCLUSION: Iron was the only micronutrient that influenced the sTfR concentration. Vitamin B(12) and folate concentrations were probably not sufficiently low to have an impact on the sTfR concentration.     

Increased serum transferrin saturation is associated with lower serum transferrin receptor concentration

BACKGROUND: Serum transferrin receptor (sTfR) concentrations are increased in iron deficiency. We wished to examine whether they are decreased in the presence of potential iron-loading conditions, as reflected by increased transferrin saturation (TS) on a single occasion. METHODS: We compared sTfR concentrations between 570 controls with normal iron status and 189 cases with increased serum TS on a single occasion; these latter individuals may be potential cases of iron overload. Cases and controls were selected from adults who had been examined in the third National Health and Nutrition Examination Survey (1988-1994) and for whom excess sera were available to perform sTfR measurements after the survey's completion. Increased TS was defined as >60% for men and >55% for women; normal iron status was defined as having no evidence of iron deficiency, iron overload, or inflammation indicated by serum ferritin, TS, erythrocyte protoporphyrin, and C-reactive protein. RESULTS: Mean sTfR and mean log sTfR:ferritin were approximately 10% and 24% lower, respectively, in cases than in controls (P <0.002). Cases were significantly more likely to have an sTfR value <2.9 mg/L, the lower limit of the reference interval, than were controls (odds ratio = 1.8; 95% confidence interval, 1.04-2.37). CONCLUSION: Our results support previous studies that suggested that sTfR may be useful for assessing high iron status in populations.     

Effect of hemochromatosis genotype and lifestyle factors on iron and red cell indices in a community population

BACKGROUND: Heterozygotes for the C282Y mutation of the HFE gene may have altered hematology indices and higher iron stores than wild-type subjects. METHODS: We performed a cross-sectional analysis of 1488 females and 1522 males 20-79 years of age drawn from the Busselton (Australia) population study to assess the effects of HFE genotype, age, gender, and lifestyle on serum iron and hematology indices. RESULTS: Male C282Y heterozygotes had increased transferrin saturation compared with the wild-type genotype. Neither male nor female heterozygotes had significantly increased ferritin values compared with the wild-type genotype. Younger (20-29 years) wild-type males, but not heterozygous males, had significantly lower ferritin values than wild-type males in the older age groups. Compound heterozygous subjects had increased means for serum iron, transferrin saturation, corpuscular volume, and corpuscular hemoglobin compared with the wild-type genotype, and the males also had increased ferritin values (medians 323 vs 177 microg/L; P = 0.003). In both male and female wild-type subjects, an increased body mass index was associated with decreased serum iron and transferrin saturation and increased ferritin values. There was a significant increase in ferritin concentrations in both genders with increasing frequency of red meat consumption above a baseline of 1-2 times per week and alcohol intakes >10 g/day. CONCLUSIONS: Male C282Y heterozygotes had significantly increased transferrin saturation values. Compound heterozygous (C282Y/H63D) subjects formed a separate category of C282Y heterozygotes in whom both iron and red cell indices were significantly increased compared with the wild-type genotype.     

Haematological laboratory findings in the elderly: influence of age and sex

The effects of age and sex on haematological laboratory parameters were studied in connection with a population study in people over the age of 65 years (n = 347). Serum vitamin B12 was the only parameter which decreased significantly with advancing age. Blood leucocyte count, haemoglobin concentration, haematocrit, erythrocyte count, mean erythrocyte volume, mean erythrocyte haemoglobin and serum ferritin values were significantly higher in males than in females. Serum iron, serum transferrin, and plasma and erythrocyte folate levels did not differ between males and females. Thirteen subjects were anaemic and three of them had iron deficiency anaemia. Five subjects had iron deficiency based on serum iron and transferrin but no anaemia. Serum ferritin measurement did not reveal any further subjects with iron deficiency. No case of folate deficiency anaemia was revealed. Although many of the participants were on medication, most of them were living at home and taking care of themselves and represent relatively fit elderly people. Therefore we suggest that these laboratory data can also serve as reference values for the elderly people.     

Reference centiles for serum ferritin and percentage of transferrin saturation, with application to mutations of the HFE gene

BACKGROUND: The gene that causes most cases of hereditary hemochromatosis is designated HFE. Individuals with mutations in the HFE gene may have increased serum iron, transferrin saturation, and ferritin concentrations relative to individuals with the wild-type genotype. METHODS: We generated reference centiles for percentage of transferrin saturation and serum ferritin concentrations in normal (wild-type), healthy Caucasian adults. We then examined transferrin and ferritin concentrations relative to these centiles in 81 individuals homozygous for the major hemochromatosis mutation C282Y and 438 individuals with the compound heterozygous HFE genotype C282Y/H63D. RESULTS: Serum ferritin concentrations, but not percentage of transferrin saturation, in normal, healthy women tended to increase sharply as they progressed through menopause. Transferrin and serum ferritin centiles for normal, healthy females were lower than the corresponding centiles in normal, healthy males. C282Y homozygotes had abnormally high transferrin saturation and serum ferritin values relative to the wild types. Compound heterozygotes appeared to be a mixture of individuals with unexceptional transferrin and ferritin values and those with abnormally large values similar to the homozygotes, with equal proportions of each. CONCLUSIONS: There are age- and sex-related differences in reference centiles for the percentage of transferrin saturation and serum ferritin concentrations in normal, healthy adults. Individuals homozygous for the C282Y mutation in the HFE gene have abnormal transferrin saturation and serum ferritin values relative to the reference population; penetrance with the compound heterozygotes, as reflected by abnormal transferrin and ferritin values, is less than with the homozygotes.     

Compound heterozygous hemochromatosis genotype predicts increased iron and erythrocyte indices in women

BACKGROUND: Women who inherit heterozygosity for the C282Y mutation of the HFE gene may have increased serum iron indices and hemoglobin and are less likely to develop iron deficiency compared with women with the wild-type genotype. METHODS: We performed a cross-sectional analysis of 497 women 20-44 years of age and 830 women >51 years of age drawn from the Busselton (Australia) population study to assess the effects of the HFE genotype on serum iron and hematology indices. RESULTS: Heterozygosity for the C282Y mutation occurred in 13.8% of the study population, comprising 11.8% C282Y wild-type heterozygotes and 2.0% C282Y/H63D compound heterozygotes. In the younger age group, C282Y wild-type women did not have significantly increased serum iron, transferrin saturation, or hemoglobin values, and were not protected from developing iron deficiency, compared with women of the same age with the wild-type genotype. Young compound heterozygous women had higher means for serum iron (25.0 vs 16.9 micromol/L; P <0.001), transferrin saturation (42.0% vs 25.6%; P <0. 05), hemoglobin (139.4 vs 132.3 g/L; P <0.05), and corpuscular volume (91.1 vs 87.7 fL; P <0.05), and a higher median ferritin (53 vs 44 microg/L; P <0.05) compared with the wild-type genotype. Similar results were observed for compound heterozygotes in the >51 years age group. CONCLUSIONS: Women with the compound heterozygous HFE genotype C282Y/H63D, but not the C282Y wild-type genotype, had increased values for serum iron and transferrin saturation, and the younger age group also had increased hemoglobin values. We conclude that the compound heterozygous genotype may have a beneficial effect in protecting women from iron deficiency.     

A nomogram to predict C282Y hemochromatosis

Genetic testing of hemochromatosis has not been widely used as a diagnostic test because of unawareness of its existence and concerns about genetic discrimination. We developed a nomogram for the prediction of C282Y homozygotes for hemochromatosis from transferrin saturation and ferritin using Bayes theorem. The results of transferrin saturation and C282Y genotyping were available for 8,572 participants (5,042 men, and 3,530 women). The study group included patients in population-screening projects, referred cases, and family members. Likelihood ratios were calculated for transferrin saturation in predicting C282Y homozygotes. Pretest probabilities were estimated on the basis of serum ferritin concentration, and a predictive nomogram for men and women was created with the use of Bayes' theorem. In the highest-risk region of the nomogram in men, the probability of C282Y hemochromatosis was 89.7% (95% confidence interval = 85.1-94.3); in the lowest-risk zone it was 1.1% (0.4-1.9). The corresponding regions in women were 88.9% in the high zone (95% confidence interval = 77.0-100.0) and 6.5% in the lowest (95% confidence interval = 4.9-8.1). This approach allows the clinician to predict the probability of a patient's being a C282Y homozygote over a wide range of ferritin and transferrin saturation values instead of above a particular threshold.     

Iron deficiency anemia

The prevalence of iron deficiency anemia is 2 percent in adult men, 9 to 12 percent in non-Hispanic white women, and nearly 20 percent in black and Mexican-American women. Nine percent of patients older than 65 years with iron deficiency anemia have a gastrointestinal cancer when evaluated. The U.S. Preventive Services Task Force currently recommends screening for iron deficiency anemia in pregnant women but not in other groups. Routine iron supplementation is recommended for high-risk infants six to 12 months of age. Iron deficiency anemia is classically described as a microcytic anemia. The differential diagnosis includes thalassemia, sideroblastic anemias, some types of anemia of chronic disease, and lead poisoning. Serum ferritin is the preferred initial diagnostic test. Total iron-binding capacity, transferrin saturation, serum iron, and serum transferrin receptor levels may be helpful if the ferritin level is between 46 and 99 ng per mL (46 and 99 mcg per L); bone marrow biopsy may be necessary in these patients for a definitive diagnosis. In children, adolescents, and women of reproductive age, a trial of iron is a reasonable approach if the review of symptoms, history, and physical examination are negative; however, the hemoglobin should be checked at one month. If there is not a 1 to 2 g per dL (10 to 20 g per L) increase in the hemoglobin level in that time, possibilities include malabsorption of oral iron, continued bleeding, or unknown lesion. For other patients, an endoscopic evaluation is recommended beginning with colonoscopy if the patient is older than 50.     

HBsAg carrier status and the association between gestational diabetes with increased serum ferritin concentration in Chinese women

OBJECTIVE: To determine whether the high prevalence of hepatitis B surface antigen (HBsAg) carriage in our population can explain the previous observation of an association between increased maternal serum ferritin concentration and gestational diabetes in Hong Kong Chinese women. RESEARCH DESIGN AND METHODS: A retrospective study was performed on 767 nonanemic women with singleton pregnancy who had iron status assessed at 28-30 weeks. The result of the routine antenatal HBsAg screening was retrieved from patient records. The HBsAg-positive and -negative groups were compared for maternal characteristics, prevalence of gestational diabetes in the third trimester, prevalence of high serum ferritin and iron concentrations, and transferrin saturation, which is defined as a value in the highest quartile established by the measurements obtained from the HBsAg-negative group. RESULTS: The incidences of oral glucose tolerance test and gestational diabetes were significantly increased in the HBsAg-positive group. The HBsAg-positive women with gestational diabetes had significantly increased prevalence of high serum ferritin compared with the HBsAg-negative women, irrespective of the latter's gestational diabetes status. Multiple logistic regression analysis confirmed the independent association between HBsAg carrier status with gestational diabetes (relative risk 3.51, 95% CI 1.83-6.73) but excluded high ferritin as an independent factor. CONCLUSIONS: Our results indicate that maternal HBsAg carriage could explain in part the association between increased serum ferritin concentration with gestational diabetes in Hong Kong Chinese women, and that HBsAg carrier status is an independent risk factor for gestational diabetes.     

Therapeutic evaluation of free and liposome-encapsulated amphotericin B in the treatment of systemic candidiasis in mice.

Various doses of amphotericin B encapsulated into unilamellar vesicles of 0.1 micron diameter (lip-AMB) (1.0 to 20.0 mg/kg of body weight) were compared with free amphotericin B (AMB) (0.5 to 2.0 mg/kg of body weight) in a murine model of disseminated candidiasis. CD2F1 mice injected intravenously with 3 x 10(5) Candida albicans cells were treated with either single- or multiple-dose regimens. Untreated infected mice had a median survival of 7 days, with all mice dead by 12 days. Single doses of AMB resulted in a median survival range from 18 to 23.5 days, with less than or equal to 38% survival by day 42. Single doses of lip-AMB resulted in 88 to 100% survival by day 42. The multiple-dose AMB regimen provided median survival of only 30 to 33 days, with less than or equal to 38% survival by day 42. The multiple-dose lip-AMB regimen resulted in greater than 90% survival by day 42. With single-dose regimens, lip-AMB levels in plasma were severalfold higher than AMB levels in plasma. By 10 h, at equivalent doses, lip-AMB levels in plasma were much higher, whereas AMB levels in plasma were not detectable. Compared with normal values, the blood urea nitrogen, serum glutamic pyruvic transaminase, serum glutamic oxaloacetate transaminase, and serum lactate dehydrogenase levels were not significantly altered by high doses of lip-AMB treatment. Viable C. albicans was recoverable from the kidneys of some of the lip-AMB-treated mice at day 42. Thus, encapsulation into unilamellar liposomes enhances the antifungal efficacy of amphotericin B while reducing the toxicity normally associated with administration of free amphotericin B.     

Serum ferritin and iron status in 'healthy' elderly individuals

Iron status, including S-ferritin, S-iron, S-transferrin, transferrin saturation and haemoglobin, was assessed in 267 selected elderly subjects (128 male, 139 female) with a median age of 79 years (range 60-93 years) not suffering from diseases connected with inappropriately high S-ferritin. In both sexes, S-ferritin levels were practically constant over the examined age range. Males had a geometric mean ferritin of 75 micrograms/l and females a value of 60 micrograms/l (p less than 0.001). Levels of S-ferritin less than 15 micrograms/l (i.e. depleted iron stores) were found in 7.8% of males and in 10.1% of females. An S-ferritin level less than 15 micrograms/l and transferrin saturation less than 15% (i.e. latent iron deficiency) was observed in 2.3% of males and in 2.2% of females. None had iron deficiency anaemia. In subjects (n = 232) without iron deficiency [i.e. S-ferritin greater than or equal to 15 micrograms/l, mean red cell volume greater than or equal to 79 fl and haemoglobin greater than or equal to 121 g/l (7.5 mmol/l)], the arithmetic mean of S-iron was 18 mumol/l. S-transferrin 28 mumol/l and transferrin saturation 33%. The levels of S-iron, S-transferrin and transferrin saturation were not significantly different in males and females.     

The relationship between red blood cell and reticulocyte indices and serum markers of iron status in the cord blood of newborns.

BACKGROUND: The aims of this study were to assess the relationship between red blood cell and reticulocyte indices and biochemical iron status measurements, and to define reference values of these markers in the cord blood of newborns. METHODS: In cord blood samples from 199 full-term newborns, cellular indices were assessed using an ADVIA 120 hematology system and iron status was analyzed by measurement of serum iron, transferrin, transferrin saturation (TfSat), transferrin receptor (TfR) and ferritin. RESULTS: Cellular hemoglobin in red blood cells or reticulocytes was independent of serum iron markers such as TfSat, TfR and ferritin. The percentage of hypochromic red blood cells (%HYPOm) and reticulocytes (%HYPOr) correlated significantly with TfSat and TfR-F index (TfR/log ferritin). Importantly, %HYPOm and %HYPOr were also positively correlated with the high immature reticulocyte fraction (IRF-H) and the mean cell volume of red or reticulocytes. CONCLUSIONS: In newborns, accelerated erythropoiesis is a major contributor to red blood cell and reticulocyte indices, which provide conflicting results when compared with serum markers of iron status. Apparently, the serum proteins ferritin, transferrin and TfR are more appropriate tools for the diagnosis of iron status in newborns.     

Blood letting in high-ferritin type 2 diabetes: effects on vascular reactivity

OBJECTIVE: In a recent study, iron chelation with deferoxamine led to improvement of endothelial dysfunction in patients with coronary artery disease. We tested the hypothesis that decreasing circulating iron stores might improve vascular dysfunction in patients with type 2 diabetes and increased serum ferritin concentration. RESEARCH DESIGN AND METHODS: A total of 28 type 2 diabetic male patients with serum ferritin levels >200 ng/ml ( approximately 18% of consecutive type 2 diabetic men attending our outpatient clinic) were randomized to iron depletion (three extractions of 500 ml blood at 2-week intervals; group 1A) or to observation (group 1B). C282Y mutation was absent in all patients. Vascular reactivity (high-resolution external ultrasound) was evaluated at baseline and at 4 and 12 months thereafter. The two groups of patients were matched for age, BMI, pharmacological treatment, and chronic diabetic complications. RESULTS: Endothelium-dependent vasodilation remained essentially unchanged in both groups of patients. In contrast, the vasodilation induced by glyceryl trinitrate (GTN) improved significantly after iron depletion (P = 0.006). These changes occurred in parallel to decreases in transferrin saturation index and HbA(1c) levels (-0.6%, P < 0.05) only in group 1A patients. The best predictor of the modifications in endothelium-independent vasodilation was the change in HbA(1c) levels. Changes in endothelium-independent vasodilation also correlated with the change in serum ferritin (r = -0.45, P = 0.04). At 12 months, transferrin saturation index and GTN-induced vasodilation returned to values similar to those at baseline in both groups of subjects. CONCLUSIONS: Iron depletion improves vascular dysfunction in type 2 diabetic patients with high ferritin concentrations. The mechanisms by which these changes occur should be further investigated.     

Usefulness of biochemical screening of diabetic patients for hemochromatosis

We assessed the prevalence of previously unrecognized hemochromatosis among patients in whom diabetes mellitus was diagnosed after the age of 30 yr, and we evaluated the positive predictive value of biochemical screening tests for hemochromatosis in diabetic subjects. Thirty-eight of 572 patients screened (6.6%) had a serum ferritin level greater than 324 micrograms/L; 16 patients had normal levels on repeat testing. Four patients' serum ferritin levels fell to less than 400 micrograms/L. Seven of 18 patients with a persistently elevated serum ferritin level did not undergo a liver biopsy because of a recognized cause of hyperferritenemia (carcinoma, alcoholism, or systemic lupus erythematosus). The diagnosis of hemochromatosis seemed certain in 1 of 3 patients who were not biopsied for technical reasons. Of 8 patients biopsied, 2 had hemochromatosis, 4 had fatty liver, 1 had hemosiderosis, and 1 had a chronic inflammatory cell infiltrate with no iron deposition. Of 4 patients with a raised transferrin saturation level, 2 had raised serum ferritin levels and hemochromatosis, 1 had raised serum ferritin and hemosiderosis on liver biopsy, and 1 had a normal transferrin saturation level on repeat testing. Two of 3 cases of hemochromatosis had other clinical markers of the condition. Therefore, routine screening of diabetic patients for hemochromatosis is not necessary, because patients with hemochromatosis will often have other clinical features of the disease. When screening diabetic patients for hemochromatosis, it should be remembered that a persistently raised serum ferritin level has a low positive predictive value (16.6%) and that a normal transferrin saturation level does not exclude the diagnosis.     

Body iron status in critically ill patients: significance of serum ferritin

Serial measurements of blood haemoglobin, serum iron, serum transferrin, total iron-binding capacity, transferrin per cent saturation and serum ferritin were determined in 51 post-operative critically ill patients to investigate body iron status in severely stressed patients. The results showed decreased blood haemoglobin, serum iron, serum transferrin and transferrin saturation compared to an increase in serum ferritin levels. These results indicate that there is inadequate availability of iron to tissues (secondary to rearrangement of body iron to the advantage of the iron storage compartment), which is often present in severely critically ill patients. A positive correlation was found between the initial (ferritin) levels and SAPS (r=0.41,p< 0.01). In addition, the increase of ferritin concentration parallels a worsening of the clinical status in severely ill patients. This is due to enhanced release by the macrophage system. From this, we consider serum ferritin as an acute-phase protein and a useful marker of the severity of the clinical status. It appears to be useful in predicting the patient's outcome, but is not reliable in evaluating iron stores in stressed patients.