Haematologica 2011; 96:1761. Parenteral therapy may be used in patients who cannot tolerate or absorb oral preparations. Assessment of iron stores using ferritin and TSAT in CICs. In addition, high hepcidin levels also block the release of ferritin-bound iron from cells of the reticuloendothelial system (e.g., macrophages) [6, 17]. MATTHEW W. SHORT, LTC, MC, USA, AND JASON E. DOMAGALSKI, MAJ, MC, USA. The diagnosis of iron deficiency anemia is confirmed by the findings of low iron stores and a hemoglobin level two standard deviations below normal. Low-molecular-weight iron deficiency, iron sucrose, and ferric gluconate may require several shorter infusions, whereas the remainder have become increasingly popular because of the lower number of visits required to administer high-dose infusions, despite the higher cost of the medication. However, the predictive power of IL-6 was weak compared to CRP. Most symptoms of iron deficiency are due to anemia. BMID is found in patients with a ferritin range between 30 and 200 g/dL and TSAT between 10% and 20%. Initial Hb response to oral iron was significantly lower in IBD patients with a high baseline CRP level (>4mg/L), compared to those with low baseline CRPat least for the first 2months of treatment. Very high levels ( above 200 mg/L) result from bacterial infections, burns and severe chronic conditions. IV iron preparations: test dose, dosage, side effects, and average wholesale pricing. With progressive iron depletion, the intracellular store of ferritin (iron-rich) is depleted, and serum ferritin (iron-poor) release by macrophages decreases proportionately, along with a progressive decrease in circulating transferrin-bound iron. Subpopulation analysis showed a significantly smaller Hb increase (p<0.05) in the high- versus low-CRP group at weeks 2, 4, and 8 among UC patients treated with oral iron (n=44; Fig. 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. This content is owned by the AAFP. Kindmark CO. Consider dietitian referral. The route of administration in CICs may shift back to oral with the ongoing success of trials of novel iron formulations that have better absorption and tolerance, such as ferric citrate (a phosphate binder approved for use in ndCKD) and ferric maltol, or those that do not depend on ferroportin (eg, Sucrosomial iron) and are currently in clinical trials.30. Responsiveness of IBD patients with high versus low baseline CRP. In patients with celiac disease, a correlation between iron deficiency and increased expression of ferritin in enterocytes of the duodenum was observed, indicating a link between iron absorption and local mucosal inflammation [20]. Other analytical methods utilizing mass spectrometry are not feasible for routine use in a hospital or outpatient setting [23]. The entered sign-in details are incorrect. This cutoff is very close to the 5mg/L cutoff which is commonly used in clinical practice to identify the presence of inflammation. Laftah AH, Sharma N, Brookes MJ, McKie AT, et al. The median baseline CRP value of the study population was applied as the cutoff value. . 1c). ACD is driven by the systemic immune response that accompanies inflammatory disease such as IBD [5]. 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). Baseline characteristic summary was described using counts for categorical variables and median and range for continuous variables. Your feedback has been submitted successfully. Theurl I, Schroll A, Nairz M, et al. Nemeth E, Tuttle MS, Powelson J, Vaughn MB, et al. Reinisch W, Staun M, Tandon RK, Altorjay I, et al. A total of 196 patients were evaluated (oral iron: n=60; i.v. If hemoglobin and red blood cell indices remain normal, one additional complete blood count should be obtained 12 months later. Bethesda, MD 20894, Web Policies Blood loss may also increase with frequent blood draws during an admission or in equipment circuits, in patients on hemodialysis, for example. 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. Correlation with absence of iron in biopsy specimens. 1000-mg single dose in 100-500 mL NS with a final concentration >1 mg iron/mL, infused over >20 min. The World Health Organization (WHO) defines anemia as hemoglobin <13 g/dL and <12 g/dL in adult men and nonpregnant women, respectively, 1 a well-known trigger for an investigation of ID. In your attached reports (attachments are hidden to protect the patient's identity) ferritin level is low, and TIBC (total-iron binding capacity) increased, which is suggestive of mild iron deficiency anemia. TSAT <25% yielded maximum sensitivity of 71%.24 In another study, BMID was identified in only 50% of patients with both TSAT <20% and ferritin <100 g/L, but TSAT <20% alone had a sensitivity of 85% and specificity of 48%.25 Those data suggest that underlying ID can still be considered in patients with CKD with TSAT of 20% to 25%, whereas for other CICs, TSAT <20% along with judicious evaluation of ferritin to diagnose ID seems appropriate. which is commonly affected by CD. The study population consisted of patients with either CD or UC, who had iron deficiency anemia (defined by Hb11g/dL and TSAT<20% or serum ferritin<100ng/mL). Not surprisingly, a trend toward a positive correlation (p=0.075) between baseline CRP and serum ferritin levels was observed in the study. Results: High serum hs-CRP (> 5 mg/l) was found in 42 (57.5 %) and anemia in 32 (43.8 %) patients. All adult men and postmenopausal women with iron deficiency anemia should be screened for gastrointestinal malignancy. 3 Animal models of hyperthyroidism demonstrate decreased circulating plasma iron and increased hepatic iron and ferritin. Ferritin reflects iron stores and is the most accurate test to diagnose iron deficiency anemia.7 Although levels below 15 ng per mL (33.70 pmol per L) are consistent with a diagnosis of iron deficiency anemia, using a cutoff of 30 ng per mL (67.41 pmol per L) improves sensitivity from 25 to 92 percent, and specificity remains high at 98 percent.8,12 Ferritin is also an acute phase reactant and can be elevated in patients with chronic inflammation or infection. Patients were stratified by baseline CRP levels into a high-CRP (>4mg/L; n=96) and a low-CRP (4mg/L; n=100) group, and responsiveness to iron supplementation (Hb change from baseline) was compared. Similarly, the median baseline IL-6 value of the study population (6pg/mL) was used for stratification into a high-IL-6 (>6pg/mL) and low-IL-6 (6 pg/mL) group. In the future, hepcidin measurement may help identify patients with significant blockade of duodenal iron absorption indicating upfront parenteral iron. 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. 2df). Oral treatment is cost effective, easily available, and should always be considered. iron: n=136). Most IBD patients become iron deficient at some stages of the disease [3, 4]. Ferritin and TSAT ranges reported by studies that evaluated BM iron in patients with CICs. 2, 94-96 In pregnancy, iron deficiency anemia is associated with increased maternal morbidity and mortality, possibly due to not being able to . iron (FCM; max 1,000mg iron per infusion at 1-week intervals until the patients calculated total iron deficit was reached) or oral iron (FS; 100mg b.i.d. Serum iron levels inversely correlated with baseline CRP. Kulnigg S, Gasche C. Systematic review: managing anaemia in Crohns disease. Among i.v. Bregman DB, Morris D, Koch TA, He A, Goodnough LT. Hepcidin levels predict nonresponsiveness to oral iron therapy in patients with iron deficiency anemia. A novel intravenous iron formulation for treatment of anemia in inflammatory bowel disease: the ferric carboxymaltose (FERINJECT) randomized controlled trial. 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. 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. Conclusion: Thus, in SLE, anaemia is the most frequent hematological alteration; iron deficiencies supercede in contrast to ACD and further autoimmune haemolytic anaemia. 2020 by The American Society of Hematology. Iron deficiency anemia (IDA) is the most commonly recognized type of anemia in . The most common side effects of current IV iron formulations are hypotension, headache, injection site reactions, and GI symptoms. Low-grade inflammation in a CIC is enough to disrupt iron metabolism by increasing hepcidin, but does not necessarily correlate with inflammatory markers. Statistical presentation includes least-squares means (LS means), standard errors (SE) split by baseline CRP or IL-6 (high vs. low) group, and associated level of significance. Author disclosure: No relevant financial affiliations to disclose. Transferrin saturation (TSAT) <6% in combination with low ferritin is diagnostic of ID, but in the presence of inflammation, a seemingly arbitrary TSAT <20% is often used to diagnose ID. Although the observed differences to the i.v. In i.v. This prospective statistical approach resulted in a cutoff at 4mg/L (high CRP: >4mg/L; low CRP: 4mg/L) and ensured an equal number of patients in both groups. Kleber Yotsumoto Fertrin; Diagnosis and management of iron deficiency in chronic inflammatory conditions (CIC): is too little iron making your patient sick?. Vegetarianism or veganism should not be considered to cause ID, because compensatory upregulation of the absorption of nonheme iron occurs. Iron deficiency is the most common nutrient deficiency worldwide. Search date: January 10, 2012. The predictive value of baseline CRP in terms of Hb response was assessed after retrospective stratification of the study population into a high-CRP and a low-CRP population. 1e, f). When symptoms occur, they're often related to blood clots. CKD patients suffer from both absolute and functional iron deficiency. With iron medication, these counts will improve. 8600 Rockville Pike the contents by NLM or the National Institutes of Health. Hypophosphatemia is usually asymptomatic, but exacerbation of symptoms of anemia may be caused by lower levels of 2,3-diphosphoglycerate in erythrocytes, an increase in hemoglobins affinity for oxygen, and limited oxygen delivery to the tissues.31 Verifying phosphate levels is recommended in symptomatic patients, in those who require repeated infusions with those compounds, or in those at higher risk for low phosphate levels (eg, patients treated with renal replacement therapy, those with chronic diarrhea, and those who have undergone a parathyroidectomy secondary to end-stage renal disease), or in those on medications associated with low absorption or increased excretion of phosphate (antacids, phosphate binders, niacin, acetazolamide, imatinib, and sorafenib). This study aimed to investigate the effect of baseline systemic inflammation (as assessed by CRP and IL-6) on the treatment efficacy of iron supplementation comparing tablets to intravenous injections. Based on the data from this relatively small patient group, patients with high CRP levels take longer to respond to oral iron but eventually reach similar responses at 3months. In . Approximately 42% of pregnant women worldwide have anemia, with iron deficiency anemia being the primary cause, and this may have a serious detrimental effect on the outcome for both mother and child. Can iron deficiency cause high CRP? Patients were stratified by baseline IL-6 levels into a high-IL-6 (>6pg/mL; n=95) and a low-IL-6 (6pg/mL; n=95) groups, and responsiveness to iron supplementation (Hb change from baseline) was compared. Patients with several comorbidities may also prefer parenteral iron to avoid adding another pill to their routine. Iron deficiency is the most common nutritional disorder worldwide and accounts for approximately one-half of anemia cases. It is the most common nutritional disorder worldwide and accounts for approximately one-half of anemia cases.1,2 Iron deficiency anemia can result from inadequate iron intake, decreased iron absorption, increased iron demand, and increased iron loss.3 Identifying the underlying etiology and administering the appropriate therapy are keys to the evaluation and management of this condition. Gasche C, Waldhoer T, Feichtenschlager T, Male C, et al. Acute-phase reactions lead to substantial changes in iron metabolism and are characterized by high levels of ferritin and hepcidin and low levels of iron and transferrin.
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