Testing should be performed in patients with signs and symptoms of anemia, and a complete evaluation should be performed if iron deficiency is confirmed.13, The American Academy of Family Physicians, U.S. Preventive Services Task Force, and Centers for Disease Control and Prevention recommend routine screening of asymptomatic pregnant women for iron deficiency anemia.4,11,14 The American College of Obstetricians and Gynecologists recommends screening for anemia and implementing iron therapy if iron deficiency anemia is confirmed.15 The defined values consistent with anemia in pregnancy are hemoglobin levels less than 11 g per dL (110 g per L) in the first or third trimester, or less than 10.5 g per dL (105 g per L) in the second trimester.16 A maternal hemoglobin level of less than 6 g per dL (60 g per L) has been associated with poor fetal outcomes, including death.15. Nevertheless, ESR varies with hematocrit and is driven mostly by the production of fibrinogen and immunoglobulins, which last for several days in the circulation, whereas CRP is mainly produced by the liver in response to cytokines, particularly IL-6, and has a much shorter half-life; discrepancies between ESR and CRP are unsurprisingly common.12 CRP >50 mg/L is frequent in bacterial infections, making it an excellent marker of acute inflammation, whereas the less-noted -1-acid glycoprotein (AGP) increases later in the inflammatory process and is more suitable for confirming chronic inflammation.13 Because ferritin increases >5 times in patients with CRP >80 mg/L than in those with CRP <10 mg/L,14 studies have examined the possibility of correcting ferritin for inflammatory activity. Patients with iron deficiency anemia are often asymptomatic and have limited findings on examination. The diagnosis of iron deficiency anemia is confirmed by the. 001) and IL-6 levels (mean difference in change: 1.33 ng/L, 95%CI 0.87-1.79, P < . Laftah AH, Sharma N, Brookes MJ, McKie AT, et al. Ferrous fumarate (Ferretts, Ferrimin, Hemocyte), 1 tablet every other day (>100 mg Fe per dose). Results: High serum hs-CRP (> 5 mg/l) was found in 42 (57.5 %) and anemia in 32 (43.8 %) patients. In the future, hepcidin measurement may help identify patients with significant blockade of duodenal iron absorption indicating upfront parenteral iron. >10%: constipation, fecal discoloration, nausea, stomach cramps, vomiting; Cereals, dietary fiber, tea, coffee, eggs, and milk may decrease absorption. Normal values for CRP range between 0.20 and 6.10mg/L [8]. A comparison between absolute ID (Figure 1) and FID (Figure 2) shows that both have low serum iron and elevated ferritin, and low TIBC characterizes FID. Weakness. WHO guidelines recommend a ferritin level <15 g/L as a sign of absolute ID in adults,8 although a cutoff of 30 g/L is more often used because of its higher sensitivity (92%) and high specificity (98%).9 Unfortunately, its high accuracy is lost in the presence of inflammation. 1-10%: fecal discoloration, constipation, diarrhea, abdominal pain, nausea, vomiting. Least-squares meansstandard errors, adjusted for gender and baseline Hb. 2020 by The American Society of Hematology. Responsiveness of IBD patients with high versus low baseline IL-6. Ferritin <30 g/L in the presence of TSAT <45% is indicative of absolute low iron stores (black). Despite a ferritin level of 89 g/L (considered normal for healthy individuals), the presence of ferritin <200 g/L, a TSAT <20% in the presence of several CICs (liver disease, controlled rheumatoid arthritis, and stage 3 ndCKD), and hypoproliferative normochromic, normocytic anemia supported a diagnosis of IDA. Conclusion: Thus, in SLE, anaemia is the most frequent hematological alteration; iron deficiencies supercede in contrast to ACD and further autoimmune haemolytic anaemia. for 12weeks) [15]. The authors acknowledge statistical support from Patrick Johnson (JPharma Solutions GmbH) and medical writing support from Bettina Barton (SFL Regulatory Affairs & Scientific Communication). Iron deficiency anemia (IDA) is the most common acquired anemia and should be the first consideration in a patient with unexplained anemia. Kulnigg S, Stoinov S, Simanenkov V, Dudar LV, et al. Intravenous iron sucrose versus oral iron supplementation for the treatment of iron deficiency anemia in patients with inflammatory bowel diseasea randomized, controlled, open-label, multicenter study. Diagnosing and treating iron deficiency become more of a challenge because markers of iron status are influenced by low-grade inflammation present in common conditions, such as chronic kidney disease, cirrhosis, or heart failure. Background: C-reactive protein (CRP) is a widely used inflammatory marker. Hepcidin binds to the iron exporter ferroportin located on the basolateral surface of gut enterocytes and causes its internalization and degradation. The search included meta-analyses, randomized controlled trials, controlled trials, and reviews. C-reactive protein (CRP) is a substance produced by the liver that increases in the presence of inflammation in the body. When you have anemia, you don't have enough hemoglobin, and so your cells aren't getting enough oxygen to function well. CRP . It affects 3% of adults and is slightly more common in women younger than 50 years. This test is a second-line technique for evaluating the small bowel because it is complicated by the level of sedation and duration of procedure.13 Magnetic resonance imaging enteroclysis, computed tomographic enterography, or barium studies may also be considered, but have a limited ability to identify most small bowel lesions, which are mucosal and flat.7. CICs caused by CKD, HF, and other disorders make the diagnosis of ID more difficult, but knowledge of how ferritin and TSAT measurements behave in concurrent CICs and ID helps identify patients who are more likely to benefit from iron supplementation. A newer formulation, ferumoxytol, can be given over five minutes and supplies 510 mg of elemental iron per infusion, allowing for greater amounts of iron in fewer infusions compared with iron sucrose.2, There are no standard recommendations for follow-up after initiating therapy for iron deficiency anemia; however, one suggested course is to recheck complete blood counts every three months for one year. Bethesda, MD 20894, Web Policies Additional laboratory results showed ferritin of 89 g/L (reference range, 20-200 g/L) and C-reactive protein (CRP) of 1.8 mg/L (reference value, <5 mg/L). doi: https://doi.org/10.1182/hematology.2020000132. . Iron is an essential mineral needed to make red blood cells, and low amounts can lead to anemia, causing headaches, pale skin, fatigue, and other symptoms. Kleber Yotsumoto Fertrin; Diagnosis and management of iron deficiency in chronic inflammatory conditions (CIC): is too little iron making your patient sick?. Overt inflammation with high ESR and CRP levels has usually been found in active autoimmune disorders (eg, Stills disease, rheumatoid arthritis, and inflammatory bowel disorders [IBDs]) and in chronic infections (eg, tuberculosis and chronic osteomyelitis). CD Crohns disease, CRP C-reactive protein, Hb hemoglobin, i.v. Second European evidence-based consensus on the diagnosis and management of ulcerative colitis part 3: special situations. Skin discoloration from extravasation is also a possible complication and patients should be informed of that particular risk. That mechanism underlies functional iron deficiency (FID; pathogenesis and management are reviewed elsewhere10). Prediction of response to iron sucrose in inflammatory bowel disease-associated anemia. Because malnutrition and inflammation are associated with low . Standardized AUC analysis confirmed a statistically significant difference between the CRP groups in oral iron-treated patients (high vs. low CRP, LS means: 21.3 vs. 29.3; p=0.012). CONCLUSIONS: Screening for iron deficiency using serum ferritin at 15 or 18 months may be a promising strategy. A ferritin test helps your doctor understand how much iron your body stores. 3-4 tablets every other day (>100 mg Fe per dose), Polysaccharide iron complex (EZFE, Ferrex, NovaFerrum), 2 tablets every other day (>100 mg Fe per dose). We also investigated baseline IL-6 levels in our study, and some significant differences between the high- and low-IL-6 groups in terms of Hb response to oral iron could be observed. Data Sources: A PubMed search was completed in Clinical Queries using the key terms iron deficiency and anemia. CRP and IL-6 values were slightly higher in CD versus UC patients, but the differences were statistically not significant (Table1). Moderate elevation refers to levels between 1.0 mg/dl and 10.0 mg/dl, which can signal a more significant issue. Response to i.v. The sensitivity of computed tomographic colonography for lesions larger than 1 cm is greater than 90 percent.7 The use of barium enema is less reliable, but may be of use if colonoscopy or computed tomographic colonography is not available. The results of this study are indicative of a significant biological effect of systemic inflammation on iron uptake, but patient numbers were relatively small. Differences were less pronounced with stratification according to baseline IL-6. Shortness of breath and nausea. We therefore recommend investigating ID in all patients with unexplained signs and symptoms of ID, regardless of the presence of anemia, low MCH, or low MCV, and in those patients with conditions that pose a higher risk for ID, either by increased iron loss (caused by chronic or recurrent bleeding and use of anticoagulants) or by reduced iron absorption (related to, eg, gastrointestinal [GI] disorders, surgical resections, or chronic use of proton pump inhibitors) (Table 1). Schroder O, Mickisch O, Seidler U, de WA, et al. 2b). A week later, she called the office to report that she was still feeling weak and wondered whether her anemia was getting worse. The concentration of C-reactive protein in sera from healthy individuals. This content is owned by the AAFP. Iron deficiency anemia was confirmed by percent transferrin saturation < 20 %. Electrophoresis The antibody produced by myeloma cells is abnormal because it is monoclonal (all the exact same ). Refer to Associated Documents for recommended daily intake values, and foods high in iron. In . government site. Patients may be asymptomatic or present with nonspecific symptoms including fatigue, irritability, and dizziness. Before Normal or high levels of ferritin do not exclude iron deficiency, because ferritin acts as an acute phase reactant. An acute-phase reaction is triggered by proinflammatory cytokines, particularly interleukin-6 (IL-6), IL-1, and tumor necrosis factor (TNF), in response to infection or tissue injury, making hepatocytes increase the synthesis of acute-phase proteins,5 including ferritin and hepcidin. Patients with several comorbidities may also prefer parenteral iron to avoid adding another pill to their routine. Because the anemia is mild and the history and laboratory values are consistent with iron. Increased CRP and significantly elevated ESR support ACD. CRP is routinely measured in IBD patients and forms part of the recommended diagnostic workup in patients with anemia (hemoglobin [Hb]<12g/dL in non-pregnant women, <13g/dL in men) [3, 9]. Elevated CRP 10 mg/L occurred in 3.3% (95% CI: 2.5 to 4.2). You may notice pale skin and cold hands and feet. Verification of phosphate levels is recommended for repeated infusions; 1-wk interval recommended before MRI. Low iron also upregulates hepatic production of transferrin, resulting in high TIBC, contributing to low TSAT. Oral treatment is cost effective, easily available, and should always be considered. A growing portfolio is currently available in the United States: low-molecular-weight iron dextran, iron sucrose, ferric gluconate, ferumoxytol, ferric carboxymaltose (FCM), and ferric derisomaltose (previously known as iron isomaltoside; Table 3). Aapro M, Osterborg A, Gascon P, Ludwig H, Beguin Y. Weiss G, Goodnough LT. 1b, p<0.05) and tended to be smaller until week 8 compared to the low-CRP group. Further evaluation should be based on risk factors (Figure 2).10,15,1721, Excessive menstruation is a common cause of iron deficiency anemia in premenopausal women in developed countries; however, a GI source (particularly erosive lesions in the stomach or esophagus) is present in 6 to 30 percent of cases.20,22,23 If the gynecologic workup is negative and the patient does not respond to iron therapy, endoscopy should be performed to exclude an occult GI source.20,22,23, Excessive or irregular menstrual bleeding affects 9 to 14 percent of all women and can lead to varying degrees of iron deficiency anemia.24 Etiologies include thyroid disease, uncontrolled diabetes mellitus, polycystic ovary syndrome, coagulopathies, uterine fibroids, endometrial hyperplasia, hyperprolactinemia, and use of antipsychotics or antiepileptics. In hepatocytes and macrophages, iron is also trapped intracellularly and is stored as iron-rich ferritin, whereas macrophages increase iron-poor serum ferritin in circulation. In the United States, the high incidence of iron-deficiency anemia in infants and children was a major public-health problem prior to the early 1970s, but now the incidence has been . >50%: fecal discoloration, abdominal pain, nausea; Ferric polymaltose (Maltofer; not available in the US). Recent data suggest that there are also other pro-inflammatory pathways modulating duodenal iron absorption. A potential relation of baseline CRP and IL-6 values with baseline Hb and iron status was investigated to assess whether these markers would be independent. Intravenous iron can for the most part overcome the hepcidin block [24] and is therefore advisable in IBD patients with pronounced disease activity [3, 9]. Differential ferritin expression is associated with iron deficiency in coeliac disease. The underlying cause should be treated, and oral iron therapy can be initiated to replenish iron stores. the contents by NLM or the National Institutes of Health. Adequate iron stores are expected in the green areas, but caution is recommended for patients in the dark green area (TSAT >20% and ferritin >500 g/L) if they are receiving parenteral iron, because they may be at risk of iatrogenic iron overload. Both ID and FID have hypoferremia but low TIBC, and high ferritin characterizes FID. Because there is a significant overlap in ferritin levels between samples with BMID and normal BM iron (range, 50-500 g/L), TSAT helps identify patients who are more likely to benefit from iron supplementation. TSAT 20% to 25% is still associated with BMID in CKD, and TSAT <20% may still predict BMID in patients with ferritin up to 500 g/L with HF or CKD treated with ESAs, with or without hemodialysis. The measurement of evaluated variables by local laboratories in this multicenter study may have added some additional variability into the data. Baseline characteristic summary was described using counts for categorical variables and median and range for continuous variables. However, the predictive power of IL-6 was weak compared to CRP. Studies that reported only ferritin levels are represented by red lines beneath the x-axis that encompass the range, and means are represented by diamonds situated on the lines. Low-grade inflammation in a CIC is enough to disrupt iron metabolism by increasing hepcidin, but does not necessarily correlate with inflammatory markers. 12- (US) to 24- (Europe) wk interval recommended before MRI. The results of this study suggest that patients with IBD and IDA, who have elevated CRP at initiation of treatment, may benefit from first-line treatment with i.v. Anemia can have many different causes. Confusion or changes in speech. 1c). Yellow striped areas represent areas in which iron supplementation may be considered, depending on the CIC; only patients with CKD are likely to benefit from iron supplementation with ferritin <200 g/L and TSAT of 20% to 25%, whereas patients with HF or CKD treated with erythropoiesis-stimulating agents (ESAs) and/or hemodialysis may be considered for iron supplementation if TSAT is <20% and ferritin is up to 500 g/L. Parenteral iron still enjoys the bad reputation of causing severe allergic reactions, mostly because of frequent reactions to high-molecular-weight iron dextran, which has been discontinued, but some manufacturers still recommend a test dose for some formulations (Table 3). iron treatment appears to be independent of inflammatory status in IBD patients. Cytokines such as IL-6 are prone to degradation, and proper handling and storage of the samples are critical for the accuracy of the measurements. 1df). Contrary to IDA, AI is moderate anemia characterized by normochromic and normocytic erythrocytes [5,21,24]. In clinical practice, CRP levels 5 mg/L are usually considered elevated. Least-squares meansstandard errors, adjusted for gender and baseline Hb. This hepcidin block during inflammation leads to diminished amounts of free iron available for erythropoiesis [5]. Statistical support and medical writing support were funded by Vifor Pharma Ltd. TI received lecture fees from Vifor Pharma Ltd and Shire Pharmaceuticals Inc. JS has received consulting fees and been a member of advisory committees or review panels of Abbott Laboratories, Falk Pharma, Ferring Pharmaceuticals Inc, Fresenius Kabi Ltd, Immundiagnostik AG, MSD, Nycomed, Shire Pharmaceuticals Inc, and Vifor Pharma Ltd. NS has no conflicts of interest to disclose. The most common indications for intravenous therapy include GI effects, worsening symptoms of inflammatory bowel disease, unresolved bleeding, renal failureinduced anemia treated with erythropoietin, and insufficient absorption in patients with celiac disease.32, Parenteral treatment options are outlined in Table 3.2,16 Serious adverse effects have occurred in up to 0.7 percent of patients receiving iron dextran, with 31 recorded fatalities reported between 1976 and 1996.32,33 Iron sucrose and sodium ferric gluconate (Ferrlecit) have greater bio-availability and a lower incidence of life-threatening anaphylaxis compared with iron dextran.2 Approximately 35 percent of patients receiving iron sucrose have mild adverse effects (e.g., headache, nausea, diarrhea).7 One small study cited similar adverse effect profiles between intravenous iron dextran and sodium ferric gluconate, with only one serious adverse effect reported in the iron dextran group.34 If this finding is duplicated in larger studies, it could support the use of iron dextran over sodium ferric gluconate, because the total dose can be given in one sitting. The Biomarkers Reflecting Inflammation and Nutrition Determinants of Anemia (BRINDA) research group found that a regression correction of ferritin using CRP >5 mg/L and AGP >1 g/L increased the prevalence of ID by 3% to 7%, even in countries with a low burden of infection, such as the United States,15,16 and a different regression correction using CRP and albumin increased the prevalence of ID from 7% to 24% in another study.17 Therefore, in areas of widespread inflammation or infection, the 2020 WHO guidelines18 strongly endorse the measurement of CRP and AGP, but make a conditional recommendation to use a ferritin threshold of 70 g/L to define iron deficiency in patients with CRP >5 mg/L or AGP >1 g/L or to implement arithmetic or regression correction of ferritin levels based on those markers. Evidence also exists that iron deficiency anemia . In ID, iron stores are progressively exhausted before red cell morphology of hemoglobin levels are affected, and patients may experience early symptoms such as fatigue, reduced cognitive performance, and exercise intolerance. Iron deficiency is characterized by microcytosis with an elevated RBC distribution width. . Serum iron levels inversely correlated with baseline CRP. There is no specific iron-containing preparation recommended to treat ID (Table 2), and evidence in pure ID/IDA supports that a single minimum dose of 60 mg of elemental iron administered on alternate days can be adequate and maximize tolerability,26,28,29 but studies in patients with CIC who are following such a regimen are lacking. Our results suggest that CRP may be useful to identify IBD patients who can benefit from first-line treatment with i.v. Prevalence and management of cancer-related anaemia, iron deficiency and the specific role of intravenous iron. If you have a Best Practice personal account, your own subscription or have registered for a free trial, log in here: If your hospital, university, trust or other institution provides access to BMJ Best Practice through services such as OpenAthens or Shibboleth, log in via this button: If you have been provided an access code, you can register it here: For any urgent enquiries please contact our customer services team who are ready to help with any problems. A ferritin test measures the amount of ferritin in your blood. The diagnosis of iron deficiency anemia is confirmed by the findings of low iron stores and a hemoglobin level two standard deviations below normal. Iron deficiency (ID) is the most common nutritional deficiency affecting children undergoing intestinal rehabilitation (IR). National Library of Medicine Change in C-Reactive . A subscription is required to access all the content in Best Practice. To be absorbed, the folate must be deconjugated by a brush border peptidase of enterocytes; the intestinal mucosal . The two most common causes of anemia in IBD patients are absolute iron deficiency and anemia of chronic disease (ACD; also referred to as anemia of chronic inflammation) [1, 3]. Parenteral iron is often used because numerous systematic reviews have identified the superiority of parenteral iron over oral iron for patients with IBD, HF, CKD, or perioperative anemia. You have had a history of viral flu. Hepcidin expression results in a reduction in the uptake of iron from the duodenum and a reduction in the ability of the body to utilize sufficient iron for effective erythropoiesisalso called functional iron deficiency [5, 6]. In clinical practice, CRP levels 5mg/L are usually considered elevated. Patient information: See related handout on iron deficiency anemia, written by the authors of this article. This material may not otherwise be downloaded, copied, printed, stored, transmitted or reproduced in any medium, whether now known or later invented, except as authorized in writing by the AAFP. C-reactive protein (CRP) is widely used as a routine marker of chronic or acute inflammation [7]. A 56-year-old woman was referred for evaluation of anemia. In patients with HF, TSAT >20% essentially excluded the possibility of BMID, regardless of ferritin levels.23 In patients with nondialysis CKD (ndCKD) who underwent BM evaluation, TSAT below 20% had only 50% sensitivity but 83% specificity to detect BMID, and the specificity for BMID improved to 98% if associated with a ferritin level <100 g/L, with a reduction in sensitivity to 33%. IBD patients with ACD had impaired oral iron absorption which correlated with disease activity and inflammatory markers but was independent of disease location and type of IBD (UC or CD). Among iron tablet-treated patients, Hb increase was significantly smaller in the high- versus low-CRP subgroup (1.1 vs. 2.0, 2.3 vs. 3.1, and 3.0 vs. 4.0g/dL at weeks 2, 4, and 8, respectively; all p<0.05). Lindgren S, Wikman O, Befrits R, Blom H, et al. For both markers, there was no significant relationship with baseline Hb levels (CRP: R=0.0191, p=0.791; IL-6: R=0.0393, p=0.590). Guidelines on the diagnosis and management of iron deficiency and anemia in inflammatory bowel diseases. Significantly impaired oral iron absorption was reported in pediatric patients (n=19) with active (defined by IL-6>5pg/mL) versus inactive CD [11]. Copyright 2013 by the American Academy of Family Physicians. In the CKD population, ferritin values vary more broadly. Patients were randomized in a 2:1 ratio to receive either i.v. She eventually completed her treatment with hemoglobin of 10.4 g/dL, ferritin of 359 g/L, and TSAT of 35%. All Rights Reserved. ACD is driven by the systemic immune response that accompanies inflammatory disease such as IBD [5]. Previously recommended, but currently not on label; >20%: hypotension, vomiting, nausea, headache, diarrhea, injection site reaction, muscle cramps; 1-10%: hypotension, edema, chest pain, hypertension, dizziness, headache, pruritus, rash, diarrhea, nausea, constipation, vomiting, abdominal pain, hypersensitivity reaction, cough, dyspnea, fever. Current guidelines recommend empiric treatment in children up to two years of age and in pregnant women with iron deficiency anemia; however, if the hemoglobin level does not increase by 1 g per dL (10 g per L) after one month of therapy in children or does not improve in pregnant women, further evaluation may be indicated.4,15,16 In pregnant patients, poor compliance or intolerance should be considered, and parenteral iron may produce a better response.15, The evaluation should begin with a thorough history and physical examination to help identify the cause of iron deficiency. Macdougall IC, Malyszko J, Hider RC, Bansal SS. SKD received speaker honoraria from Vifor International. Anemia of chronic disease (ACD, also called anemia of inflammation [AI], anemia of chronic inflammation, or hypoferremia of inflammation) was initially thought to be associated primarily with infectious, inflammatory, or neoplastic disease. The correlation between the degree of inflammation and response to oral or i.v. iron-treated patients, there were no significant differences between the high- and low-CRP groups at weeks 1, 4, and 12 (Fig. In line with these results, standardized AUC showed no statistically significant differences between high- and low-CRP groups in i.v. Ten deceased patients with dialytic CKD and BMID had ferritin values between 537 and 3994 g/L; the researchers acknowledged that 4 of the patients had rare minute deposits of iron, but even assuming they would have the highest ferritin values, the maximum value of ferritin in a patient with BMID with dialytic CKD would be in the 1000 to 2000 g/L range.20 Another study found that 3 of 96 patients were receiving hemodialysis with BMID, with ferritins in the 100 to 1100 g/L range.21 More recent studies reported ferritin of 36 to 100 g/L in HIV+ patients with BMID, of whom half had a diagnosis of tuberculosis or Epstein-Barr viremia, and >25% had CMV viremia.22 In HF, patients with true BMID were found to have ferritin levels ranging from 44 to 162 g/L (interquartile range).23 Except in patients with CKD and some with HF, patients with BMID in CICs appear to have a ferritin level rarely >200 g/L. Chest pain. Iron supplementation is recommended in all types of IBD-associated anemia where iron deficiency is present [2, 3, 9]. High intracellular iron also downregulates transferrin production, lowering TIBC. Various ferritin cutoff values have been recommended to help detect ID in different patient populations, such as in those with CKD, HF, and IBD.3 There is a general consensus that the usual ferritin cutoff of 30 g/L is inappropriate in the presence of a CIC but the recommended ferritin values range between 50 and 500 g/L across guidelines. 2a), apart from early response in the CD subpopulation (p<0.05 at week 2; Fig. which is commonly affected by CD. Iron-deficiency anemia is usually discovered during a medical examination through a blood test that measures . Copyright 2023 by American Society of Hematology, Out of Balance: Anemias Due to Disordered Iron Homeostasis, Ferritin in CIC: making the best of an imperfect tool, Transferrin saturation in CIC: a helping hand, Adverse events with IV iron supplementation and management, https://doi.org/10.1182/hematology.2020000132, http://www.who.int/vmnis/indicators/haemoglobin, https://www.who.int/publications/i/item/9789240000124, Anorexia/GI tract edema; frequent use of proton pump inhibitors; use of phosphate chelators; high hepcidin with blockade of duodenal absorption, Uremic platelet dysfunction; antiplatelet therapy and anticoagulation; blood loss from hemodialysis, Anorexia/GI tract edema; high hepcidin with blockade of duodenal absorption, High hepcidin with blockade of duodenal absorption; small bowel resection, Chronic diarrhea with high epithelial turnover; GI tract bleeding; use of corticosteroids, High hepcidin due to adipose tissue inflammation; bariatric surgery, Increased uterine bleeding (when associated with polycystic ovarian syndrome), Anorexia/GI tract edema; diarrhea caused by laxatives, Variceal bleeding; thrombocytopenia; coagulopathy, High hepcidin with blockade of duodenal absorption.
