Compound Heterozygous Hemochromatosis Genotype Predicts Increased Iron and Erythrocyte Indices in Women

Abstract 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 μmol/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 μg/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.

Download Full-text

Reference Centiles for Serum Ferritin and Percentage of Transferrin Saturation, with Application to Mutations of the HFE Gene

Clinical Chemistry ◽

10.1093/clinchem/47.10.1804 ◽

2001 ◽

Vol 47 (10) ◽

pp. 1804-1810 ◽

Cited By ~ 36

Author(s):

James A Koziol ◽

Ngoc J Ho ◽

Vincent J Felitti ◽

Ernest Beutler

Keyword(s):

Serum Ferritin ◽

Hereditary Hemochromatosis ◽

Transferrin Saturation ◽

Reference Population ◽

Hfe Gene ◽

Compound Heterozygous ◽

Wild Type ◽

C282y Mutation ◽

Compound Heterozygotes ◽

Healthy Females

Abstract 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.

Download Full-text

Heterozygosity for the C282Y mutation in the hemochromatosis gene is associated with increased serum iron, transferrin saturation, and hemoglobin in young women: a protective role against iron deficiency?

Clinical Chemistry ◽

10.1093/clinchem/44.12.2429 ◽

1998 ◽

Vol 44 (12) ◽

pp. 2429-2432 ◽

Cited By ~ 73

Author(s):

Christian Datz ◽

Thomas Haas ◽

Heinrich Rinner ◽

Friedrich Sandhofer ◽

Wolfgang Patsch ◽

...

Keyword(s):

Iron Deficiency ◽

Young Women ◽

Serum Iron ◽

Transferrin Saturation ◽

Protective Role ◽

Hfe Gene ◽

Wild Type Allele ◽

Wild Type ◽

C282y Mutation ◽

Type Allele

Abstract Genetic hemochromatosis (GH) is the most common autosomal-recessive disorder (1 in 300 in populations of Celtic origin). Homozygosity for a C282Y mutation in the hemochromatosis (HFE) gene is the underlying defect in ∼80% of patients with GH, and 3.2–13% of Caucasians are heterozygous for this gene alteration. Because the high frequency of this mutation may result from a selection advantage, the hypothesis was tested that the C282Y mutation confers protection against iron deficiency in young women. To address this question the genotype of codon 282 was determined in a cohort of 468 unrelated female healthcare workers, ages 18–40 years. In all study participants, a complete blood count was obtained, and erythrocyte distribution width, serum iron, transferrin, transferrin saturation, and ferritin were measured. Two individuals were homozygous for the C282Y mutation, 44 were heterozygous, and 416 were homozygous for the wild-type allele. Heterozygous women had significantly higher values for hemoglobin (P = 0.006), serum iron (P = 0.013), and transferrin saturation (P = 0.006) than women homozygous for the wild-type allele. Our data provide evidence for a protective role of the C282Y mutation in the HFE gene against iron deficiency in young women and suggest that a more efficient utilization of nutritional iron may have contributed to the high prevalence of the mutation in Caucasian populations.

Download Full-text

Effect of Hemochromatosis Genotype and Lifestyle Factors on Iron and Red Cell Indices in a Community Population

Clinical Chemistry ◽

10.1093/clinchem/47.2.202 ◽

2001 ◽

Vol 47 (2) ◽

pp. 202-208 ◽

Cited By ~ 64

Author(s):

Enrico Rossi ◽

Max K Bulsara ◽

John K Olynyk ◽

Digby J Cullen ◽

Lesa Summerville ◽

...

Keyword(s):

Serum Iron ◽

Transferrin Saturation ◽

Age Groups ◽

Hfe Gene ◽

Compound Heterozygous ◽

Red Cell ◽

Wild Type ◽

Cross Sectional ◽

Red Cell Indices ◽

Sectional Analysis

Abstract 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 μg/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.

Download Full-text

Tmprss6 Is a Genetic Modifier of the Hfe-Hemochromatosis Phenotype in Mice.

Blood ◽

10.1182/blood.v114.22.625.625 ◽

2009 ◽

Vol 114 (22) ◽

pp. 625-625

Author(s):

Karin E. Finberg ◽

Rebecca Whittlesey ◽

Mark D. Fleming ◽

Nancy C. Andrews

Keyword(s):

Iron Deficiency ◽

Iron Content ◽

Serum Iron ◽

Iron Concentration ◽

Transferrin Saturation ◽

Heme Iron ◽

Deficiency Anemia ◽

Wild Type ◽

Non Heme Iron ◽

Serum Iron Concentration

Abstract Abstract 625 HFE-associated hereditary hemochromatosis is an autosomal recessive disorder characterized by inappropriately elevated absorption of dietary iron by the gastrointestinal mucosa, resulting in excessive storage of iron in multiple organs. A significant proportion of individuals who are homozygous for HFE mutations fail to develop clinical symptoms, suggesting that environmental and/or genetic factors may influence the penetrance of this disorder. In vitro and animal studies have revealed that HFE promotes the expression of hepcidin, a circulating hormone produced by the liver that acts to inhibit iron absorption by the duodenum. In contrast, TMPRSS6, a transmembrane serine protease produced by the liver, acts to inhibit hepcidin expression; both humans and mice harboring TMPRSS6 mutations display impaired intestinal iron absorption, resulting in a phenotype of iron-refractory iron deficiency anemia (IRIDA). Here we asked if heterozygous or homozygous loss of Tmprss6 function could modify the iron overload phenotype of Hfe null (Hfe-/-) mice, a mouse model of human HFE-hemochromatosis. To test this, we bred Hfe-/- mice to Tmprss6-/- mice; the latter harbor a targeted disruption of the Tmprss6 serine protease domain and exhibit an IRIDA phenotype. We generated Hfe-/-Tmprss6+/+, Hfe-/-Tmprss6+/-, and Hfe-/-Tmprss6-/- female mice (6-10 mice per genotype), in which parameters of systemic iron homeostasis were compared at eight weeks of age by Student's t test. Consistent with previous study of Hfe-/- mice, Hfe-/- mice harboring two wild type Tmprss6 alleles (Hfe-/-Tmprss6+/+ mice) showed serum iron concentration, transferrin saturation, and hepatic non-heme iron content that were significantly elevated compared to wild type mice of similar genetic background. Heterozygosity for Tmprss6 mutation, however, markedly reduced the severity of the hemochromatosis phenotype of Hfe-/- mice. Compared to Hfe-/- mice with two wild type Tmprss6 alleles, Hfe-/- mice that were heterozygous for Tmprss6 mutation (Hfe-/-Tmprss6+/- mice) showed significant reductions in serum iron concentration (p<0.01), transferrin saturation (p<0.005), and non-heme iron content of liver (p<10-4). Furthermore, homozygosity for Tmprss6 mutation completely ameliorated the iron overload phenotype of Hfe-/- mice and in fact led to systemic iron deficiency. Compared to both Hfe-/-Tmprss6+/+ and Hfe-/-Tmprss6+/- mice, Hfe-/-Tmprss6-/- mice showed markedly reduced serum iron concentration (p<10-7), transferrin saturation (p<10-10), and non-heme iron content of liver (p<10-4). Hfe-/-Tmprss6-/- mice also displayed iron deficiency anemia and appeared phenotypically similar to previously characterized Tmprss6-/- mice harboring two wild type copies of Hfe. In summary, these results demonstrate that Tmprss6 is a genetic modifier of the Hfe-hemochromatosis phenotype in mice. These findings suggest that natural genetic variation in the human ortholog TMPRSS6 might modify the clinical penetrance of HFE-hemochromatosis and raise the possibility that pharmacological inhibition of TMPRSS6 activity might prove an effective therapy in this disorder. Disclosures: No relevant conflicts of interest to declare.

Download Full-text

Serum iron and total iron-binding capacity compared with serum ferritin in assessment of iron deficiency.

Clinical Chemistry ◽

10.1093/clinchem/27.2.276 ◽

1981 ◽

Vol 27 (2) ◽

pp. 276-279 ◽

Cited By ~ 15

Author(s):

F Peter ◽

S Wang

Keyword(s):

Iron Deficiency ◽

Serum Ferritin ◽

Serum Iron ◽

Binding Capacity ◽

Transferrin Saturation ◽

Total Iron ◽

Iron Binding ◽

Total Iron Binding Capacity ◽

Iron Deficient ◽

Iron Binding Capacity

Abstract Ferritin values for 250 selected sera were compared with values for iron, total iron-binding capacity (TIBC), and transferrin saturation, to assess the potential of the ferritin assay for the detection of latent iron deficiency. The specimens were grouped (50 in each group) according to their values for iron and TIBC. In Group 1 (low iron, high TIBC) the saturation and ferritin values both indicated iron deficiency in all but one. In the 100 specimens of Groups 2 (normal iron, high TIBC) and 4 (normal iron, high normal TIBC), the saturation values revealed 16 iron-deficient cases, the ferritin test 55. For Groups 3 (low iron, normal TIBC) and 5 (low iron, low TIBC), the ferritin test revealed fewer cases of iron deficiency than did the saturation values (37 cases vs 51 cases, in the 100 specimens). Evidently the ferritin test detects iron deficiency in many cases for whom the serum iron and TIBC tests are not positively indicative. The correlation of serum ferritin with iron, TIBC, and transferrin saturation in the five groups was good only in the case of specimens for which the TIBC was normal; if it was abnormal the correlation was very poor.

Download Full-text

Iron Deficiency Anemia Following Prenatal Nutrition Interventions

Canadian Journal of Dietetic Practice and Research ◽

10.3148/68.4.2007.222 ◽

2007 ◽

Vol 68 (4) ◽

pp. 222-225

Author(s):

Caroline P. Leblanc ◽

France M. Rioux

Keyword(s):

Iron Deficiency ◽

Pregnant Women ◽

Iron Deficiency Anemia ◽

Low Income ◽

Mean Corpuscular Volume ◽

Serum Iron ◽

Transferrin Saturation ◽

Deficiency Anemia ◽

Corpuscular Volume ◽

Prevalence Of Anemia

Purpose: Iron deficiency anemia (IDA) during pregnancy and infancy is still common in developed countries, especially in low-income groups. We examined the prevalence of anemia and IDA in healthy low-income pregnant women participating in the Early Childhood Initiatives (ECI) program, and in their infants when they reached six months of age. Methods: Pregnant women were recruited by nutritionists. In mothers, hemoglobin (Hb), mean corpuscular volume, and serum ferritin (SF) were measured at 36 ± 2 weeks of gestation. In infants, Hb, mean corpuscular volume, SF, serum iron, total iron binding capacity (TIBC), and transferrin saturation (TS) were measured at six months of age. Thirty-one mother-infant pairs participated. Results: Among the 31 pregnant women participating in the ECI program, six (19.4%) were anemic (Hb <110 g/L) and five (16.1%) suffered from IDA (Hb <110 g/L and SF <10 µg/L). Among infants, seven of 23 (30.4%) were anemic (Hb <110 g/L) and five of 23 (21.7%) suffered from IDA (Hb <110 g/L plus two of the following: TIBC >60 µmol/L, SF <10 µg/L, serum iron <5.3 µmol/L, TS ≤15%). Conclusions: The prevalence of anemia in this group of lowincome pregnant women is comparable to that in privileged women. The prevalence of IDA in infants is comparable to that observed in other high-risk groups. Effective strategies are needed to prevent IDA in vulnerable groups.

Download Full-text

Subclinical Iron Deficiency in Non-Anemic Individuals: A Retrospective Analysis of Korean Health Examinees

Acta Haematologica ◽

10.1159/000500630 ◽

2019 ◽

Vol 143 (1) ◽

pp. 26-32

Author(s):

Eun-Hee Nah ◽

Han-Ik Cho ◽

Seon Cho ◽

Suyoung Kim

Keyword(s):

Iron Deficiency ◽

Blood Cell ◽

Serum Iron ◽

Binding Capacity ◽

Transferrin Saturation ◽

Reproductive Age ◽

Iron Level ◽

Distribution Width ◽

Elderly Males ◽

Males And Females

Objectives: Non-anemic individuals may have undetected subclinical iron deficiency (SID). The aims of this study were to determine the prevalence of SID and identify the associated factors for SID. In addition, the screening performance of red blood cell (RBC) indices for SID in health check-ups was assessed. Methods: This study was conducted with 16,485 non-anemic health examinees (3,567 males and 12,918 females) who underwent tests for iron variables (serum iron, total iron-binding capacity, ferritin, and iron saturation) at 16 health-promotion centers in 13 cities in Korea between January 2017 and June 2018. SID was defined as a decreased ferritin level (<24 µg/L in males and <15 µg/L in females) and either a decreased serum iron level (<44 µg/dL in males and <29 µg/dL in females) or a transferrin saturation of <20%. Results: The prevalence rates of SID were 0.6 and 3.3% in males and females, respectively. In terms of age and sex, SID was most prevalent in males aged ≥70 years (7.8%) and females aged 15–49 years (7.6%). There were significant differences in the hemoglobin (Hb) level, white blood cell count, platelet count, mean corpuscular volume, mean corpuscular Hb (MCH), and RBC distribution width (RDW) between the SID and non-SID groups (p < 0.001). The factors associated with SID in males were older age (odds ratio, OR, 1.069, 95% confidence interval, CI, 1.03–1.109, p = 0.004), lower Hb (OR 0.58, 95% CI 0.345–0.976, p = 0.04), lower MCH (OR 0.433, 95% CI 0.298–0.629, p < 0.001), and higher RDW (OR 1.374, 95% CI 1.001–1.887, p = 0.049), while in females they were lower body mass index (BMI; OR 0.929, 95% CI 0.895–0.963, p < 0.001) and younger age (OR 0.954, 95% CI 0.945–0.963, p < 0.001), as well as lower Hb, lower MCH, and higher RDW. The AUC for the MCH (0.877, 95% CI 0.793–0.960 in males; 0.872, 95% CI 0.853–0.890 in females) indicates that the MCH at cut-offs of 29.2 and 29.3 pg are the best discriminators of SID in males and females, respectively (p < 0.001). Conclusions: Reproductive-age females with a lower BMI and elderly males are high-risk groups for SID. MCH is a reliable RBC index for the screening of SID. For the population with defined risk factors, including females with lower BMI and elderly males, screening for SID is needed to prevent the development of anemia.

Download Full-text

Iron Overload in C282Y Heterozygotes: Identification of New Rare HFE Gene Mutants and a Step Strategy for Diagnosis.

Blood ◽

10.1182/blood.v112.11.1859.1859 ◽

2008 ◽

Vol 112 (11) ◽

pp. 1859-1859

Author(s):

Patricia Aguilar-Martinez ◽

Severine Cunat ◽

Fabienne Becker ◽

Francois Blanc ◽

Marlene Nourrit ◽

...

Keyword(s):

Iron Overload ◽

Iron Status ◽

Hereditary Hemochromatosis ◽

Genetic Defect ◽

Transferrin Saturation ◽

Hfe Gene ◽

Compound Heterozygous ◽

Exon 2 ◽

High Iron ◽

Iron Parameters

Abstract Introduction: Homozygozity for the p.Cys282Tyr (C282Y) mutation of the HFE gene is the main genotype associated with the common form of adult hereditary hemochromatosis. C282Y carriers do not usually develop iron overload, unless they have additional risk factors such as liver diseases, a dysmetabolic syndrome or an associated genetic defect. The commonest is the compound heterozygous state for C282Y and the widespread p.His63Asp (H63D) variant allele. However, a few rare HFE mutations can be found on the 6th chromosome in trans, some of which are of clinical interest to fully understand the disorder. Patients and Methods: We recently investigated four C282Y carrier patients with unusually high iron parameters, including increased levels of serum ferritin (SF), high transferrin saturation (TS) and high iron liver content measured by MRI. They were males, aged 37, 40, 42, 47 at diagnosis. Two brothers (aged 40 and 42) were referred separately. The HFE genotype, including the determination of the C282Y, H63D and S65C mutations was performed using PCR-RFLP. HFE sequencing was undertaken using the previously described SCA method (1). Sequencing of other genes (namely, HAMP, HJV/HFE2, SLC40A1, TFR2) was possibly performed in a last step using the same method. Results: We identified three rare HFE mutant alleles, two of which are undescribed, in the four studied patients. One patient bore a 13 nucleotide-deletion in exon 6 (c.[1022_1034del13], p.His341_Ala345>LeufsX119), which is predicted to lead to an abnormal, elongated protein. The two brothers had a substitution of the last nucleotide of exon 2 (c.[340G>A], p.Glu114Lys) that may modify the splicing of the 2d intron. The third patient, who bore an insertion of a A in exon 4 (c.[794dupA],p.[trp267LeufsX80]), has already been reported (1). Discussion: A vast majority of C282Y carriers will not develop iron overload and can be reassured. However, a careful step by step strategy at the clinical and genetic levels may allow to correctly identify those patients deserving further investigation. First, clinical examination and the assessment of iron parameters (SF and TS) allow identifying C282Y heterozygotes with an abnormal iron status. Once extrinsic factors such as heavy alcohol intake, virus or a dysmetabolic syndrome have been excluded, MRI is very useful to authenticate a high liver iron content. Second, HFE genotype must first exclude the presence of the H63D mutation. Compound heterozygozity for C282Y and H63D, a very widespread condition in our area, is usually associated with mild iron overload. Third, HFE sequencing can be undertaken and may identify new HFE variants as described here. The two novel mutations, a frameshift modifying the composition and the length of the C terminal end of the HFE protein and a substitution located at the last base of an exon, are likely to lead to an impaired function of HFE in association with the C282Y mutant. However, it is noteworthy that three of the four patients were diagnosed relatively late, after the 4th decade, as it is the case for C282Y homozygotes. Three further unrelated patients are currently under investigation in our laboratory for a similar clinical presentation. Finally, it can be noted that in those patients who will not have a HFE gene mutant identified, analysis of other genes implicated in iron overload must be performed to search for digenism or multigenism. None of our investigated patients had an additional gene abnormality.

Download Full-text

Interaction Between Genotypes for HFE and TFR2 Genes Mutations and Iron Status in Brazilian Blood Donors

Blood ◽

10.1182/blood.v112.11.5382.5382 ◽

2008 ◽

Vol 112 (11) ◽

pp. 5382-5382

Author(s):

Rodolfo D Cancado ◽

Paulo CJL Santos ◽

Samuel Rostelato ◽

Cristiane T Terada ◽

Iris Gonzales ◽

...

Keyword(s):

Serum Ferritin ◽

Serum Iron ◽

Blood Donors ◽

Binding Capacity ◽

Iron Status ◽

Hereditary Hemochromatosis ◽

Transferrin Saturation ◽

The Body ◽

Hfe Gene ◽

Automation System

Abstract Hereditary hemochromatosis (HH) is a disorder characterized by increased intestinal iron absorption, which leads to a progressive accumulation of iron in the body. This iron overload has been associated with mutations in HFE gene (C282Y, H63D and S65C) and other genes. The objectives of this study were to assess the frequencies of functional mutations in HFE and TFR2 genes and to investigate their relationship with the iron status in a sample of blood donors. Blood donors (n=542) were recruited at the Hemocenter of the Santa Casa Hospital, Sao Paulo, Brazil. The genotypes for HFE (C282Y, H63D and S65C) TFR2 (Y250X and Q690P) gene mutations were evaluated by PCR-RFLP. The concentrations of serum iron and total iron-binding capacity (TIBC) were measured by automation system Advia®(Bayer Diagnostics) and serum ferritin by Axsym System®(Abbott Laboratories). The frequencies of HFE 282Y, HFE 63D and HFE 65C alleles were 2.1, 13.6 and 0.6%, respectively. The frequency C282Y allele (2.1%) in Brazilian blood donors is lower than that observed in blood donors from Northern Europe (5.1 to 8.2%, P<0.05). The TFR2 250X and TFR2 690P alleles were not found in these subjects. The iron status was similar between HFE genotypes in women. However, men carrying HFE 282CY genotype had higher serum ferritin and lower TIBC concentrations when compared to the HFE 282CC genotype carriers. HFE 282CY genotype was also associated with higher transferrin saturation in men who donated blood at the first time. Moreover, male donors with HFE 63DD plus 63HD genotypes had higher serum iron and transferrin saturation when compared to those with HFE 63HH genotype. A relationship between HFE CY/HH/SS haplotype and lower TIBC concentrations was also found in men. The HFE 282Y and HFE 65C alleles were rare while the HFE 63D was frequent in blood donors. The mutations in TFR2 gene were not found in this study. The HFE 282Y and HFE 63D alleles were associated with alterations on iron status only in male blood donors.

Download Full-text

High Prevalence of Iron Deficiency In Anemic and Non Anemic Patients with Various Types of Cancer

Blood ◽

10.1182/blood.v116.21.5145.5145 ◽

2010 ◽

Vol 116 (21) ◽

pp. 5145-5145

Author(s):

Heinz Ludwig ◽

Georg Endler ◽

Brigitte Klement ◽

Wolfgang Hüubl ◽

Tim Cushway

Keyword(s):

Iron Deficiency ◽

Serum Ferritin ◽

Multiple Testing ◽

Serum Iron ◽

Iron Supplementation ◽

Complete Blood Count ◽

Clinical Symptoms ◽

Iron Status ◽

Transferrin Saturation ◽

Patients With Cancer

Abstract Abstract 5145 Introduction and aims: Iron deficiency as a major component in the pathogenesis of anemia in cancer is not acknowledged by most oncologists, possibly except when arising from GI blood loss. Iron deficiency is associated with clinical symptoms such as cognitive impairment, fatigue, and reduced exercise performance. New iron formulations are available that allow rapid iron supplementation with single infusions. This treatment could ameliorate symptoms of iron deficiency and correct anemia. Here, we studied iron parameters and their correlation with erythropoiesis and inflammatory markers in a large unselected cohort of patients with cancer. In addition, we investigated the suitability of serum ferritin and transferrin saturation (TSAT) as parameter for assessment of the iron status. Patients and methods: Data from 1627 patients (median age: 66.4 years, range: 20–97 years) presenting sequentially at the Center for Oncology and Hematology, Wilhelminenspital, Vienna between October 01, 2009 and January 26, 2010, have retrospectively been analyzed. Patients were at different stages of their disease or may not have had an established diagnosis at the time of testing. In patients with multiple testing during this period only the first sample taken was included. TSAT (n=1516), serum ferritin (n=887), serum iron, CRP, and complete blood count, were determined by using standard techniques. Commonly used definitions for absolute iron deficiency (AID), [TSAT <20% and serum ferritin <30ng/ml, in case serum ferritin was not available TSAT <10%] and for functional iron deficiency (FID), [TSAT <20% and serum ferritin ≥30ng/ml, in case serum ferritin was not available TSAT between 10 and 20%] have been applied. Fisher's exact test was used for comparison of frequencies and Pearson's product moment correlation coefficient for evaluation of correlation. Results: Table 1 shows the distribution of TSAT and serum ferritin categories in 1627 patients with cancer. AID was found in 116 patients (7.7%) of the 1516 patients for whom TSAT was available. Eighty-three (72%) of the AID patients presented with anemia (defined by hemoglobin <12g/dl). AID was most common in patients with colorectal and pancreatic cancer (12% and 11%, respectively), and not present in patients with testicular and prostate cancer (p=0.013). FID was diagnosed in 530 patients (35%) and 222 (42%) of them were found to be also anemic. Multivariate analysis revealed a statistically significant correlation between TSAT and serum ferritin (R=0.286, p<0.001), serum iron (R=0.874, p<0.001), hemoglobin (R=0.201, p<0.001) and CRP (R=-0.205, p<0.001) (figure 1). Serum ferritin, in contrast, did not correlate with serum iron (R=0.051, p=0.132), but correlated with hemoglobin (R=-0.259, p<0.001), TSAT (R=0.286, p<0.001), and CRP (R=0.396, p<0.001). Conclusion: AID (7.7%) and even more so FID (35%) are frequent co-morbidities in patients with various types of cancer. Seventy-two percent of patients with AID and 42% with FID presented with overt anemia. TSAT correlated closely with serum iron and hemoglobin levels and seems to be the preferred parameter for assessment of iron status in patients with chronic diseases often complicated by increased inflammation. Serum ferritin was found to be an inadequate parameter for assessment and monitoring of iron status. As iron deficiency has been linked with various symptoms, the question arises whether iron supplementation would benefit patients with FID without overt anemia. Future studies should evaluate the role of novel intravenous iron preparations in ameliorating the symptoms of iron deficiency with or without anemia. Disclosures: Klement: Vifor Pharma Ltd: Employment. Cushway:Vifor Pharma Ltd.: Employment.

Download Full-text