Anemia in Crohn's disease

Intestinal blood loss as well as chronic inflammation are regarded as the most important mechanisms in the pathogenesis of anemia in Crohn's disease. In addition, cytokines such as interleukin-6 can suppress erythropoietin production. This study was performed to investigate the importance of iron status, inflammatory activity, and endogenous erythropoietin concentrations for the development of anemia in Crohn's disease. In 49 consecutive patients with Crohn's disease, hemoglobin, inflammatory activity (Crohn's disease activity index, C-reactive protein, α₁-acid glycoprotein), iron status (serum iron, transferrin, transferrin saturation, ferritin), and serum erythropoietin levels were studied. Anemic (Hb<12.0 g/dl;N=16) vs nonanemic patients (Hb≥12 g/dl;N=33) showed reduced iron compartments (eg, ferritin 28.7±12.9 µg/liter vs 63.2±15.0 µg/liter, transferrin saturation 6.2±1.4% vs 11.5±1.3%,P<0.01) but no differences in inflammatory activity. An inverse correlation between erythropoietin and hemoglobin concentrations was found (r=-0.62;P<0.001), but the increase in erythropoietin levels was inadequate to the degree of anemia. There was no correlation between erythropoietin and interleukin-6 serum levels. Four of five anemic patients with hemoglobin below 10.5 g/dl and erythropoietin levels within the normal range were treated with parenteral iron (200 mg iron saccharate in 250 ml NaCl, weekly, intravenously). Two of them additionally received recombinant human erythropoietin (150 units/kg, 3× weekly, subcutaneously). After five weeks all patients had a marked increase in hemoglobin. However, the mean increase in erythropoietin-treated patients was 5.0 g/dl compared to 2.0 g/dl in the patients with iron therapy only. No side effects were seen. Our data demonstrate that inadequate erythropoietin production and iron deficiency are pathogenetic factors of anemia in Crohn's disease. The therapeutic management using recombinant human erythropoietin and parenteral iron is reasonable and effective.     

Autologous blood donation for surgery in inflammatory bowel disease--a report of six cases

BACKGROUND: Surgery in inflammatory bowel disease (IBD) is frequently associated with need for perioperative blood transfusions carrying the potential risk of infection. Autologous blood donation is often limited by IBD-associated anemia which is reversible by intravenous iron and erythropoietin. We therefore tested the feasibility of autologous blood donation in IBD. METHODS: Six patients (five Crohn's disease, one ulcerative colitis) with indication for elective bowel resection were treated after informed consent was obtained. Two to four blood donations were scheduled during four weeks prior to surgery. Once a week 350-450 ml of blood were collected from patients with a hemoglobin level above 11.0 g/dl. After each donation 200 mg of iron saccharate diluted in 0.9% saline were given to all patients intravenously as substitute for donation-related iron loss. Patients with preexisting anemia or C-reactive protein above 2.0 mg/dl received concomitant erythropoietin. RESULTS: The scheduled number of packed red cells was donated successfully by four patients. Due to low hemoglobin levels two patients donated one unit less than intended. Four patients received autologous blood transfusions intra- or postoperatively. No patient needed homologous blood. No serious adverse events were observed during blood donations, perioperatively, and during the one year follow-up period. CONCLUSION: Preoperative autologous blood donation is save and feasible in IBD patients with elective bowel resection.     

Effectiveness of darbepoetin-alfa in combination with intravenous iron sucrose in patients with inflammatory bowel disease and refractory anaemia: a pilot study

BACKGROUND: The combination of intravenous iron and recombinant human erythropoietin has been proved to be effective in the treatment of refractory anaemia in patients with inflammatory bowel disease (IBD). Darbepoetin-alpha (DPO) has a three-fold longer terminal half-life than erythropoietin. The purpose of this pilot study was to determine whether darbepoetin-alpha is also effective for the treatment of refractory anaemia in IBD. METHODS: Twenty IBD patients (nine ulcerative colitis and 11 Crohn's disease) and refractory anaemia received intravenous iron sucrose (total iron dose 1.3+/-0.5 g, range 0.7-1.9) and darbepoetin-alfa at the single, weekly dose of 0.9 microg/kg subcutaneously for 4 weeks. Serum erythropoietin, ferritin, transferrin, soluble transferrin receptor, C-reactive protein and interleukin-6 were measured at baseline and after treatment. RESULTS: Haematopoietic response (increase of haemoglobin > or = 2.0 g/dl) was observed in 15 out of the 20 patients (75%). The mean haemoglobin concentrations increased from 9.48+/-0.82 g/dl at baseline to 12.71+/-1.12 g/dl after treatment (P<0.0001). Mean corpuscular volume and serum ferritin levels were also significantly increased whereas mean C-reactive protein levels and endogenous erythropoietin levels significantly decreased after treatment. CONCLUSIONS: In IBD patients with refractory anaemia the administration of darbepoetin in combination with intravenous iron sucrose can raise haemoglobin levels.     

Variable efficacy of recombinant human erythropoietin in anemic pregnant women with different forms of heterozygous hemoglobinopathy

OBJECTIVE: The aim of this study was to determine the response to recombinant human erythropoietin (rhEPO) in anemic pregnant women with heterozygous hemoglobinopathies. METHODS: A prospective study including 19 consecutive pregnant women with anemia and heterozygous hemoglobinopathy was performed. Treatment was divided into two phases: the initial low-dose phase and the subsequent high-rhEPO phase. In the initial phase, 3 x 10,000 U of rhEPO was administered with intravenous iron sucrose. In patients showing a poor response (Hb increase <1 g/dl) to low-dose rhEPO, the rhEPO dose was increased to 20,000 U per treatment in the subsequent phase. RESULTS: All patients showed stimulation of erythropoiesis as evidenced by an increase in hemoglobin. In 13 patients, a good response to therapy was observed (mean Hb increase 1.6 +/- 0.5 g/dl). In 6 patients, resistance to rhEPO was noted (mean Hb increase 0.5 +/- 0.5 g/dl). The mean gestational age at the start of therapy was 28 weeks of gestation and at the end 32 weeks. The mean duration of a complete therapy was 3.5 weeks (range 2-4.5 weeks). If calculated for body weight, the initial low- rhEPO dose of 160.4 +/- 30.6 U/kg body weight/treatment was increased to 320.9 +/- 61.2 U/kg body weight/treatment in the subsequent phase. CONCLUSION: Response to rhEPO treatment differs widely in anemic pregnant patients with heterozygous hemoglobinopathy. Resistance was observed in anemic pregnant patients with the beta-thalassemia trait originally from the Mediterranean region.     

Prediction of response to iron sucrose in inflammatory bowel disease-associated anemia

OBJECTIVE: Inflammatory bowel disease (IBD)-associated anemia responds to i.v. iron therapy. However, because of concurrent chronic inflammation, some patients do not respond adequately. Erythropoietin therapy has been shown to be effective in the latter cohort. Our goal was to find parameters that can predict the effectiveness of iron sucrose in IBD-associated anemia. METHODS: One hundred three patients with severe IBD-associated anemia (Hb < or = 10.5 g/dl) were treated prospectively for 4 wk with iron sucrose (total iron dose = 1.2 g) in an open label, multicenter trial. Treatment response was defined as an increase in Hb of > or =2.0 g/dl. A logistic regression analysis was performed with treatment response as the dependent variable and the following independent variables: serum erythropoietin, mean corpuscular Hb, transferrin, ferritin, soluble transferrin receptor (sTfR), C-reactive protein, interleukin 6 (IL-6), and disease activity. RESULTS: Sixty-seven of 103 patients (65%) responded to iron sucrose. From the variables under investigation, erythropoietin, sTfR, transferrin, and IL-6 were significantly associated with treatment response. The R2 values showed that erythropoietin (8.0%), sTfR (11.4%), and transferrin (10.4%), but not IL-6 (1.3%), contribute a relevant amount of information to the model. An estimated 80% probability of treatment response was found at erythropoietin levels of >166 U/L, sTfR levels of >75 nmol/L, or transferrin levels of >3.83 g/L. CONCLUSIONS: Serum erythropoietin, sTfR, and transferrin concentrations have the potential to predict the response to iron sucrose therapy in IBD-associated anemia. These parameters may help to identify individuals who benefit the most from additional erythropoietin treatment.     

Intravenous iron alone for the treatment of anemia in patients with chronic heart failure.

OBJECTIVES: This study was undertaken to assess the hematologic, clinical, and biochemical response to intravenous iron in patients with chronic heart failure (CHF) and anemia. BACKGROUND: Anemia is common in patients with CHF and is associated with higher morbidity and mortality. The combination of erythropoietin (EPO) and iron increases hemoglobin (Hb) and improves symptoms and exercise capacity in anemic CHF patients. It is not known whether intravenous iron alone is an effective treatment for anemia associated with CHF. METHODS: Sixteen anemic patients (Hb < or =12 g/dl) with stable CHF (age 68.3 +/- 11.5 years, 12 men, 9 participants New York Heart Association [NYHA] functional class II and the remainder class III, left ventricular ejection fraction 26 +/- 13%) received a maximum of 1 g of iron sucrose by bolus intravenous injections over a 12-day treatment phase in an outpatient setting. Mean follow-up was 92 +/- 6 days. RESULTS: Hemoglobin rose from 11.2 +/- 0.7 to 12.6 +/- 1.2 g/dl (p = 0.0007), Minnesota Living with Heart Failure (MLHF) score fell (denoting improvement) from 33 +/- 19 to 19 +/- 14 (p = 0.02), 6-min walk distance increased from 242 +/- 78 m to 286 +/- 72 m (p = 0.01), and all patients recorded NYHA class II at study end (p < 0.02). Changes in MLHF score and 6-min walk distance related closely to changes in Hb (r = 0.76, p = 0.002; r = 0.56, p = 0.03, respectively). Of all baseline measurements, only iron and transferrin saturation correlated with increases in Hb (r = 0.60, p = 0.02; r = 0.60, p = 0.01, respectively). There were no adverse events relating to drug administration or during follow-up. CONCLUSIONS: Intravenous iron sucrose, when used without concomitant EPO, is a simple and safe therapy that increases Hb, reduces symptoms, and improves exercise capacity in anemic patients with CHF. Further assessment of its efficacy should be made in a multicenter, randomized, placebo-controlled trial.     

Effects of parathyroidectomy on iron homeostasis and erythropoiesis in hemodialysis patients with severe hyperparathyroidism

AIMS: Secondary hyperparathyroidism (HPT) worsens anemia and may cause hyporesponsiveness to recombinant human erythropoietin therapy (r-HuEPO). To investigate the effect of parathyroidectomy (PTX) on iron homeostasis and erythropoiesis, we conducted a prospective study in chronic hemodialysis patients who underwent PTX. METHODS: Thirty-two patients were enrolled in this study. Based on the increases in hemoglobin level after PTX, patients were divided into responders and nonresponders. Iron homeostasis and erythropoiesis were assessed before and 1 and 3 months after PTX, hemoglobin and parathyroid hormone levels were monitored until 6 months after PTX. RESULTS: In the responders, increased hemoglobin levels were observed in 15 patients at 1 and 3 months after PTX (8.0 +/- 0.8 g/dl vs. 9.2 +/- 1.3 and 10.1 +/- 0.9 g/dl, p < 0.05). The nonresponders had higher pre-PTX hemoglobin levels than the responders (10.3 +/- 1.6 g/dl vs. 8.0 +/- 0.8 g/dl, p < 0.05). There was no further increase in hemoglobin at 6 months compared to 3 months after PTX in both groups. In neither group did PTX affect serum ferritin, transferrin saturation and serum erythropoietin level. Serum soluble transferrin receptor (sTfR) concentration was found to be higher in responders than in nonresponders (3.32 +/- 1.28 mg/l vs. 1.70 +/- 0.31 mg/l, p < 0.05). CONCLUSIONS: We conclude that PTX can improve anemia in hemodialysis patients with severe hyperparathyroidism and greater resistance to r-HuEPO therapy. The reversing of anemia does not involve altering iron mobilization. Pre-PTX hemoglobin and serum sTfR levels can predict the effect of PTX on correcting anemia.     

Defective iron supply for erythropoiesis and adequate endogenous erythropoietin production in the anemia associated with systemic-onset juvenile chronic arthritis

Systemic-onset juvenile chronic arthritis (SoJCA) is associated with high levels of circulating interleukin-6 (IL-6) and is frequently complicated by severe microcytic anemia whose pathogenesis is unclear. Therefore, we studied 20 consecutive SoJCA patients with hemoglobin (Hb) levels <12 g/dL, evaluating erythroid progenitor proliferation, endogenous erythropoietin production, body iron status, and iron supply for erythropoiesis. Hb concentrations ranged from 6.5 to 11.9 g/dL. Hb level was directly related to mean corpuscular volume (r = .82, P < .001) and inversely related to circulating transferrin receptor (r = - .81, P < .001) suggesting that the severity of anemia was directly proportional to the degree of iron-deficient erythropoiesis. Serum ferritin ranged from 18 to 1,660 microgram/L and was unrelated to Hb level. Bone marrow iron stores wore markedly reduced in the three children investigated, and they also showed increased serum transferrin receptor and normal-to-high serum ferritin. All 20 patients had elevated IL-6 levels and normal in vitro growth of erythroid progenitors. Endogenous erythropoietin (epo) production was appropriate for the degree of anemia as judged by both the observed to predicted log (serum epo) ratio 10.95 +/- 0.12) and a comparison of the serum epo- Hb regression found in these subjects with that of thalassemia patients. Multiple regression analysis showed that serum transferrin receptor was the parameter most closely related to hemoglobin concentration: variation in circulating transferrin receptor explained 61% of the variation in Hb level (P < .001). In 10 severely anemic patients, amelioration of anemia following intravenous iron administration resulted in normalization of serum transferrin receptor. Defective iron supply to the erythron rather than blunted epo production is the major cause of the microcytic anemia associated with SoJCA. A true body-iron deficiency caused by decreased iron absorption likely complicates long-lasting inflammation in the most anemic children, and this can be recognized by high serum transferrin receptor levels. Although oral iron is of no benefit, intravenous iron saccharate is a safe and effective means for improving iron availability for erythropoiesis and correcting this anemia. Thus, while chronically high endogenous IL-6 levels do not appear to blunt epo production, they are probably responsible for the observed abnormalities in iron metabolism. Anemia of chronic disease encompasses a variety of anemic conditions whose peculiar features may specifically correlate with the type of cytokine(s) predominantly released.     

Comparison of the serum erythropoietin levels in chemotherapy-naive and cisplatin-treated cancer patients

There are conflicting data about the effects of cisplatin on erythropoietin (EPO) response to anemia. Aim of our study was to investigate whether endogenous EPO response to anemia in cisplatin treated patients was insufficient in comparison to the anemic chemotherapy-naive cancer patients and non cancer patients with iron deficiency anemia. Patients who had hemoglobin (Hb) levels of less than 110 g/l were included in the study. Fifteen chemotherapy- naive cancer patients were enrolled in Group A. Group B consisted of 15 patients who had been treated with three cycles of cisplatin chemotherapy and then became anemic and in Group C were included 15 patients who had iron deficiency anemia, without any malignancy. The mean Hb values were not different between all groups (102.8+/-39.8 g/l, 103.1+/-2.5 g/l and 99.3+/-3.6 g/l in Group A, Group B and Group C, respectively). However, EPO levels were found to be significantly lower in Group A and Group B than Group C (29.63+/-9.09 mU/ml, 20.87+/-2.43 mU/ml and 85.38+/-25.72 mU/ml, respectively; p=0.017 Group A vs. Group C, p=0.005 Group B vs. Group C). No significant difference was found between Group A and B (p=0.917). Opposite the iron deficiency anemia, cancer anemia is associated with an inadequate EPO response to anemia and administration of cisplatin does not lead to it further deterioration.     

Prevalence, prognostic importance and therapeutic implications of anemia in heart failure

BACKGROUND: Despite advances in its management, heart failure, once established, remains highly prevalent and lethal. Anemia can exacerbate the hemodynamic burden in heart failure. The present study was undertaken to assess the presence of anemia and analyze how its control impacts the outcome in heart failure patients. METHODS AND RESULTS: From a cohort of 238 heart failure patients, 55 (231%) patients were found to be anemic. Twenty-nine patients (Group A) were given recombinant human erythropoietin for 12 weeks along with iron, and followed up for a mean period of 24 +/- 6 months. The patients improved substantially in terms of functional capacity (6 min walk test improved from 232 +/- 35 m to 278 +/- 41 m, p < 0.001), hemoglobin level from 10.1 +/- 0.90 gm/dl to 12 +/- 0.7 gm/dl, (p < or = 0.001), and ejection fraction from 33 +/- 7.1% to 41 +/- 6.9% (p < or = 0.001). Twenty-six patients (Group B) who were age- and sex-matched with Group A and had similar degree of functional disability and left ventricular dysfunction as that of Group A were not given erythropoietin and iron. Thus, Group B patients served as controls. In comparison to Group B, Group A patients demonstrated not only higher hemoglobin level (12 +/- 0.7 gm/dl v. 9.8 +/- 0.9 gm/dl, p < or = 0.001), and ejection fraction (41 +/- 6.9% v. 26 +/- 7%, p < or = 0.05), but also better survival (16/29 v. 7/26, p < 0.05, odds ratio 1.27). CONCLUSIONS: Anemia is a significant predictor of poor outcome in patients with heart failure. Administration of erythropoietin can correct anemia and help improve survival.     

Serum erythropoietin levels in the elderly.

We evaluated the relationship between erythropoietin (EPO) and hemoglobin (Hb) concentrations in 156 normal subjects ranging from 60 to 98 years old. EPO was determined by a radioimmunoassay. The serum EPO concentration in subjects with Hb concentrations greater than 12.0 g/dl (26.9 +/- 15.2 mU/ml), was significantly higher than that in younger controls (15.8 +/- 5.0 mU/ml, p less than 0.001). No sex difference in serum EPO level was detected. In addition, there was an inverse semilogarithmic relationship between EPO and Hb concentrations in subjects with Hb concentrations less than 12.0 g/dl (r = -0.559, p less than 0.001). EPO concentrations in the elderly were lower than those in young subjects with iron deficiency anemia with the same Hb level. Thus, in the elderly, a high EPO concentration may be preventing a decrease in the Hb concentration. However, a decreased EPO response to low Hb concentrations may be a contributing factor in anemia in the elderly.     

Effects of intravenous iron saccharate on improving severe anemia in rheumatoid arthritis patients

Anemia in rheumatoid arthritis (RA) is multifactorial. Iron deficiency, either definite or relative (defect in iron utilization), exists in RA patients with anemia. Intravenous iron therapy is indicated in severe and symptomatic cases or those with conditions precluding use of oral iron, but its safety and long-term efficacy have not been well-established. Forty severe anemic (hemoglobin < 9 g/dL) RA patients with or without demonstrable bone marrow iron stain were enrolled in this study. Fractionated administration of intravenous iron saccharate was undertaken and the median follow-up time was 1 year. All patients exhibited significant elevations of hemoglobin 3 months after treatment, which were more pronounced in the nonstainable iron marrow subjects {median (interquartile range): 3.8 (2.9–4.8) g/dL versus 2.9 (2.0–3.0) g/dL, p < 0.01}. Thereafter, hemoglobin remained at a plateau level that lasted during the observation period. Throughout the whole course, none of the cases exhibited side effects or flare up of disease activities. The use of intravenous iron saccharate, preferably administrated in a fractionated way, is effective in the correction of severe anemia in RA patients, especially those with nonstainable iron marrow.     

Anemia in patients with ulcerative colitis in remission: A study from western India

Background

Anemia is common in patients with active ulcerative colitis. We aimed to study the anemia profile in patients with ulcerative colitis in clinical remission.

Methods

Sixty-four patients with ulcerative colitis and with a clinical Mayo score less than 3 for at least 3 months were evaluated for anemia. Initial screening was done by hemogram and only patients with anemia were evaluated further for the cause of anemia. We also screened a control population for anemia. Patients with mild anemia were given oral iron, moderate anemia were given intravenous iron and severe anemia were given blood transfusion.

Results

The mean hemoglobin in ulcerative colitis patients was 11.75 g/dL and in controls was 13.1 g/dL (p=0.011). The prevalence of anemia was 53.1% in the ulcerative colitis patients and 13.3% in the controls (p=<0.001). 58.8% had mild anemia, 29.4% had moderate anemia and 8.8% had severe anemia. Iron deficiency was the most common cause of anemia (70.5%) followed by anemia of chronic disease combined with iron deficiency in 23.5%. Ferritin levels did not correlate with hemoglobin levels. Oral iron increased the hemoglobin by 1.4 g/dL and intravenous iron by 2.2 g/dL at 1 month.

Conclusion

Anemia was seen in more than half of patients with ulcerative colitis in clinical remission, iron deficiency being the most common cause.

     

Etiology of anemia in patients with advanced heart failure.

OBJECTIVES: We prospectively investigated the causes of anemia in patients with advanced congestive heart failure (CHF). BACKGROUND: Anemia is common in patients with advanced CHF, and its etiology is generally considered to be multifactorial. However, despite its importance, precise information is lacking regarding the prevalence of putative etiologic factors. METHODS: Patients who were hospitalized for decompensated advanced CHF and who were stabilized after their initial treatment underwent evaluation of "clinically significant" anemia, defined as a hemoglobin content <12 g/dl for men and <11.5 g/dl for women. Patients with a serum creatinine concentration >3 mg/dl or patients with concurrent diseases that are known to cause anemia were not included. The initial evaluation included measurements of vitamin B(12), folic acid, thyroid-stimulating hormone, erythropoietin, lactate dehydrogenase, Coombs test, multiple fecal occult tests, and bone marrow aspiration. Patients without diagnosis by these methods underwent red cell mass measurement with (51)Cr assay. RESULTS: The mean age of the 37 patients was 57.9 +/- 10.9 years and mean left ventricular ejection fraction 22.5 +/- 5.9%. Iron deficiency anemia was confirmed by bone marrow aspiration in 27 patients (73%), 2 patients (5.4%) had dilutional anemia, and 1 patient (2.7%) had drug-induced anemia. No specific cause was identified in 7 patients (18.9%) who were considered to have "anemia of chronic disease." Serum ferritin for the iron-deficient patients was not a reliable marker of iron deficiency in this population. CONCLUSIONS: In this group of patients, iron deficiency was the most common cause of anemia. The iron status of patients with end-stage chronic CHF should be thoroughly evaluated and corrected before considering other therapeutic interventions.     

Improvement of anemia in hemodialysis patients treated by hemodiafiltration with high-volume on-line-prepared substitution fluid

BACKGROUND: Hemodiafiltration (HDF) is associated with a lower incidence of neuropathy, carpal tunnel syndrome, joint pain, and partial correction of anemia. HDF with on-line-prepared substitution fluid (OL HDF), as compared with conventional hemodialysis, increases the treatment tolerance and, as compared with standard HDF, avoids storage problems and allows a higher substitution volume at low cost. METHODS: Thirty-two hemodialysis patients treated by OL HDF for at least 9 months were studied. Hemoglobin, hematocrit, iron metabolism, serum albumin, dialysis dose and dry body weight were determined under a settled condition with regular hemodialysis 3 months before the transfer to OL HDF. The same parameters were analyzed 3, 6 and 9 months after the beginning of the new treatment modality. RESULTS: During OL HDF, hemoglobin values significantly increased in patients without addition of recombinant human erythropoietin (rHuEPO): baseline vs. 6 months 11 +/- 1.7 vs. 12 +/- 1.8 g/dl (p < 0.01); baseline vs. 9 months 11 +/- 1.7 vs. 12 +/- 1.6 g/dl (p < 0.05). In patients on a maintenance dose of rhuEPO, this could be significantly reduced, while the target hemoglobin levels were maintained (10.6 +/- 0.9 g/dl): baseline 99.8 +/- 50.4 U/kg/week, 3rd month 76.2 +/- 43 U/kg/week, 6th month 64.3 +/- 37 U/kg/week, and 9th month 59.4 +/- 38.6 U/kg/week (p = 0.007, p = 0.0006, and p = 0.0007, respectively, vs. baseline). Iron metabolism, dialysis dose, dry body weight and serum albumin levels did not significantly change during the follow-up period. Further, a stability of the rHuEPO supplementation was observed in 14 patients followed up for 24 months. CONCLUSIONS: OL HDF influences anemia and rHuEPO dose. It allows considerable anemia correction in patients without rHuEPO treatment, while it significantly reduces rHuEPO doses in those on rHuEPO treatment as compared with standard hemodialysis. The rHuEPO costs are consequently reduced.     

Pediatric Crohn's disease,iron deficiency anemia and intravenous iron treatment: a follow-up study

Background and aims: Increasing evidence in adults demonstrates efficacy and safety of IV iron in inflammatory Bowel disease (IBD) associated iron deficiency anemia; however, evidence in pediatric patients is yet scarce and no previous study has included a long follow-up. This study aimed to evaluate safety and efficacy of IV iron (primary end point), and the need of re-treatment (secondary end point), in this setting.

Methods: Prospective recruitment (40 months); PCDAI determined before and after treatment; anemia defined according to WHO criteria; IV iron treatment included iron sucrose and ferric carboxymaltose. Primary and secondary endpoints included hemoglobin, serum ferritin, transferrin saturation at baseline and 4-6 weeks after treatment; and the need of re-treatment during the median follow-up period (18 months), respectively.

Results: Nineteen patients (median age: 15.5 years) with remissive/mild disease were included. At recruitment, the median hemoglobin was 10.5?g/dl, (median s-ferritin: 20.1 ug/l, median transferrin saturation; 6%) and 4-6 weeks after treatment was 12.7?g/dl. Median hemoglobin according to age groups before vs. after treatment:?<12 years:11 vs. 12.0?g/dl; females ≥12 years:9.9 vs. 12.6?g/dl; and males ≥12 years:11.1 vs. 13.3?g/dl. Patients with remissive vs. mild disease had median Hb of 10.5?g/dl vs. 10.6?g/dl, and median s-ferritin: 6.8 ug/dl vs. 43.3 ug/dl, respectively). Nine patients were treated with iron sucrose (median dose 672.6?mg/dl) and 10 patients with ferric carboxymaltose (median dose 811.5?mg/dl). No major adverse reactions occurred. Six patients needed re-treatment after a median 15.5 months period.

Conclusions: Our prospective study, concerning pediatric IBD anemia patients with remission/mild disease and a significant follow-up, emphasizes efficacy and safety of IV-iron and the importance of long-term follow-up of iron status.

Summary: In pediatric IBD iron anemia, the evidence supporting the efficacy and safety of IV-iron is scare. This prospective study aims to evaluate the safety and efficacy (short and long term) of IV-iron in these patients. Nineteen pediatric CD patients were evaluated before and after IV iron treatment (40-month period).The median Hb before and after IV iron was 10.5 and 12.7?g/dl, respectively. No major adverse reactions were documented. Six patients needed re-treatment (median period of 15.5 months). This study further demonstrates the efficacy and safety of IV iron. It reinforces the importance of long-term follow-up of the iron status in pediatric CD patients.     

Effect of recombinant human erythropoietin and intravenous iron on anemia and disease activity in rheumatoid arthritis.

OBJECTIVE: To investigate whether treatment of anemia of chronic disease (ACD) in patients with rheumatoid arthritis (RA) with recombinant human erythropoietin (rHu-Epo) in combination with intravenous (i.v.) iron influences health related quality of life (HRQoL) and clinical outcome including disease activity. METHODS: Thirty patients with ACD and RA were treated with 150 IU/kg rHu-Epo twice weekly for 12 weeks. As well, in case of functional iron deficiency 200 mg of iron-sucrose per week was given intravenously. Vitality and fatigue as dimensions of HRQoL were evaluated by the vitality subscale of the Short Form-36 (SF-36-VT) and the Multidimensional Assessment of Fatigue (MAF). Muscle strength was measured by the Muscle Strength Index. RESULTS: All 28 patients completing the study responded to treatment; 23/28 patients developed functional iron deficiency and received i.v. iron (mean absolute dose 710 +/- 560 mg). Average hemoglobin concentration increased from 10.7 +/- 1.1 to 13.2 +/- 1.0 g/dl after a mean treatment period of 8.7 +/- 2.3 weeks. Muscle strength increased from 43.5 +/- 11.2 to 49.1 +/- 12.9 and SF-36-VT from 28.2% +/- 14.3% to 47.1% +/- 20.8%. while fatigue decreased (MAF from 34.7 +/- 9.3 to 25.0 +/- 11.3). Among the disease activity variables the number of swollen/tender joints, erythrocyte sedimentation rate, Disease Activity Score, and RA Disease Activity Index improved significantly during treatment. CONCLUSION: Treatment of ACD in RA patients with rHu-Epo and i.v. iron is safe and effective in correction of anemia, increases muscle strength. improves vitality, and lowers fatigue. In addition we observed a reduction of disease activity.     

Anemia of chronic disease is the more frequent type of anemia seen in patients with chronic idiopathic neutropenia of adults

This study describes the frequency and the type of anemia seen in patients with nonimmune chronic idiopathic neutropenia of adults (NI-CINA). We found that NI-CINA patients had low hemoglobin levels and increased serum concentrations of erythropoietin (EPO), tumor necrosis factor-alpha (TNF-alpha), and interleukin-1beta (IL-1beta). The hemoglobin levels correlated positively with the number of circulating neutrophils and inversely with the levels of EPO and TNF-alpha but not of IL-1beta. Anemia, defined as the reduction of the hemoglobin below 12.0 g/dl for women and 13.3 g/dl for men, was found in 23 out of 148 patients studied, a proportion of 15.5%. Two of the anemic patients had iron deficiency anemia (8.7%), 11 had anemia of chronic disease (ACD; 47.8%) presenting with normal or slightly reduced erythrocytic indices, low serum iron, and increased serum ferritin, and the remaining ten had anemia of undefined pathogenesis (AUP; 43.5%) with normal or slightly decreased erythrocytic indices, serum iron ranging from 43 to 88 microg/dl, and ferritin values ranging from 12 to 50 ng/ml. We conclude that ACD is the more frequent type of anemia seen in patients with NI-CINA, and that pro-inflammatory cytokines, notably TNF-alpha, may be involved in the pathogenesis of both ACD and AUP, given that serum levels of the cytokine were significantly increased and that the EPO response to anemia was blunted in these patients. These findings further support our previously reported suggestion for the possible existence, in NI-CINA patients, of an unrecognized low-grade chronic inflammatory process that may be involved in the pathogenesis of the disorder.     

Erythropoietic response to anemia in chronic hepatitis C patients receiving combination pegylated interferon/ribavirin

OBJECTIVES: In hepatitis C virus (HCV)-infected patients receiving pegylated interferon (PEG-IFN)/ribavirin (RBV) combination therapy, anemia is a well-known side effect. The purpose of this study was to describe the time course and extent of hemoglobin (Hb) changes and the erythropoietic response to PEG-IFN/RBV-induced anemia. METHODS: In this multicenter, observational, 8-wk study, laboratory parameters were measured weekly for 8 wk or until early withdrawal. Primary endpoints included changes in Hb and serum erythropoietin (sEPO) from baseline to week 8; other measures were changes in reticulocytes and RBV dose. The predictive value of baseline factors for maximum Hb decline was assessed. RESULTS: In the 97 evaluable patients, mean Hb decreased from 14.4 +/- 1.4 g/dl (baseline) to 11.9 +/- 1.3 g/dl (week 8). Twenty-one percent of patients withdrew before week 8. The estimated erythropoietic response was lower than that seen in two historic control populations of iron deficiency anemia patients. Mean RBV dose decreased from 986 +/- 190 mg/day (baseline) to 913 +/- 228 mg/day (week 8). Fifty-seven out of 77 (74%) patients who completed the study maintained their initial prescribed RBV dose. Patients maintained on the initial dose of RBV who had a higher baseline Hb and viral load showed a trend toward larger Hb declines. Platelets and white blood cells (WBCs) also declined during the study. CONCLUSIONS: HCV-infected patients receiving PEG-IFN/RBV therapy have reductions in Hb, platelets, and WBCs, possibly due to bone marrow suppression. They also have diminished endogenous sEPO production for their degree of anemia.     

Effective therapy of human immunodeficiency virus-associated anemia with recombinant human erythropoietin despite high endogenous erythropoietin

A 32-year-old woman with human immunodeficiency virus (HIV) infection and progressive anemia presented to University Hospital with a hemoglobin of 3.4 g/dl. Because of her religious beliefs, she refused transfusion, and no iron or vitamin deficiency was found. She responded to recombinant human erythropoietin 150 U/kg intramuscularly thrice weekly with a rise in hemoglobin to 9.3 g/dl by 3 months of treatment. The serum erythropoietin level before treatment was markedly elevated at 1,340 mU/ml.