Ret-Y a measure of reticulocyte size: a sensitive indicator of iron deficiency anemia

In this study the size of reticulocytes was measured, reticulocyte-Y (Ret-Y), to distinguish iron deficiency anemia from the anemia of chronic disease using a Sysmex XE2100 cell counter. We evaluated this parameter prospectively in 100 patients seen for the evaluation of anemia. A clinical diagnosis of iron deficiency anemia or anemia of chronic disease was made on the basis of a complete blood count, examination of the peripheral smear, and serum ferritin along with a history and physical examination. We analyzed the sensitivity and specificity of the Ret-Y in relationship to the clinical diagnosis. We also measured serum transferrin receptor levels to use as the gold standard laboratory test for iron deficiency against which we compared the Ret-Y. In 40 normal individuals with normal serum ferritin and transferrin receptor levels the mean Ret-Y was 1874 +/- 178 (1 SD). The mean Ret-Y in the anemia of chronic disease group (n=62) was 1722 +/- 162, not significantly different from normal. The mean Ret-Y value among iron-deficient patients (n=38), was 1407 +/- 136 (P <0.01 vs. the anemia of chronic disease group's Ret-Y value). Receiver operator curves showed that Ret-Y correlated closely to the serum transferrin receptor and was superior to the mean corpuscular volume, and ferritin level, in differentiating the type of anemia. The Ret-Y parameter has the highest overall sensitivity and specificity of the panel of tests routinely used in differentiating iron deficiency anemia from anemia of chronic disease.     

Sideroblast score: A sensitive indicator of iron deficiency and hypoproliferative anemia.

The detection and enumeration of sideroblasts depend critically on the method used for iron staining of bone marrow smears. Several methods proposed for semiquantitative evaluation of bone marrow hemosiderin (iron stores) were compared with respect to their suitability for detection of normal and abnormal sideroblasts. Instead of the customary percentage of sideroblasts, the introduction of a sideroblast score is proposed and its diagnostic relevance was prospectively studied. Low sideroblast scores are associated with iron deficiency and hypoproliferative anemia. A normal sideroblast score, despite the absence of stainable hemosiderin, exclused the diagnosis of severe iron depletion. Elevated sideroblast scores may be correlated either with iron overload and/or sideroblastic (sideroachrestic) anemias.     

Gluten sensitive enteropathy in patients with iron deficiency anemia of unknown origin

AIM： To determine the prevalence of gluten sensitive enteropathy （GSE） in a large group of patients with iron deficiency anemia （IDA） of obscure origin.METHODS： ：In this cross-sectional study, patients with IDA of obscure origin were screened for GSE. Anti- endomysial antibody （EMA） and tissue transglutaminase antibody （tTG） levels were evaluated and duodenal biopsies were taken and scored according to the Marsh classification. The diagnosis of GSE was based on a positive serological test and abnormal duodenal histology. Gluten free diet （GFD） was advised for all the GSE patients.RESULTS： Of the 4120 IDA patients referred to our Hematology departments, 206 （95 male） patients were found to have IDA of obscure origin. Thirty out of 206 patients （14.6%） had GSE. The mean age of GSE patients was 34.6± 17.03 （range 10-72 years）. The female to male ratio was 1.3：1. Sixteen patients had Marsh 3,12 had Marsh 2, and 2 had Marsh 1 lesions. The severity of anemia was in parallel with the severity of duodenal lesions. Twenty-two GSE patients （73.3%） had no gastrointestinal symptoms. Fourteen GSE patients who adhered to GFD without receiving iron supplementation agreed to undergo follow up visits. After 6 mo of GFD, their mean hemoglobin levels （Hb） increased from 9.9 ±1.6 to 12.8 ±1.0 g/dL （P 〈 0.01）. Interestingly, in 6 out of 14 patients who had Marsh 1/2 lesions （e.g. no villous atrophy） on duodenal biopsy, mean Hb increased from 11.0 ±1.1 to 13.1 ±1.0 g/dL （P 〈 0.01） while they did not receive any iron supplementation. CONCLUSION： There is a high prevalence （e.g. 14.6%） of GSE in patients with IDA of obscure origin. Gluten free diet can improve anemia in GSE patients who have mild duodenal lesions without villous atrophy.     

Usefulness of measuring reticulocyte hemoglobin equivalent in the management of haemodialysis patients with iron deficiency

The evaluation of iron status in dialysis patients provides information essential to the planning of adequate recombinant human erythropoietin treatment. The cellular iron status of the patients can be determined from the recently available measurement of reticulocyte hemoglobin equivalent (RET-He). RET-He is measured on the basis of automated fluorescent flow cytometry which in the reticulocyte channel, using a polymethine dye, also measures the mean value of the forward light scatter intensity of mature red blood cells and reticulocytes. These values equate with reticulocyte hemoglobin content. In this study, to clarify the accuracy of RET-He in diagnosing iron deficiency in dialysis patients, we initially compared RET-He with such iron parameters as serum ferritin levels, transferrin saturation and content of reticulocyte hemoglobin (CHr) which has been established as indicators of functional iron deficiency. Secondly, we investigated the changes in RET-He during iron supplementation for iron-deficient patients to determine whether this marker is a prospective and reliable indicator of iron sufficiency. The participants in this study were 217 haemodialysis patients. Iron deficiency was defined as havsing a transferrin saturation (TSAT) < 20% or serum ferritin < 100 ng/ml. Conventional parameters of red blood cells and RET-He were measured by on a XE-2100 automated blood cell counter (Sysmex). CHr was measured on an ADVIA120 autoanalyser (Siemens). RET-He mean value was 32.4 pg and good correlation (r = 0.858) between RET-He and CHr is obtained in dialysis patients. Receiver operating characteristic curve analysis revealed, values of the area was 0.776 and at a cutoff value of 33.0 pg, a sensitivity of 74.3% and a specificity of 64.9%, were achieved. Iron supplements given to the patients with low TSAT or ferritin, RET-He responded within 2 weeks, and this seemed to be a potential advantage of using RET-He in the estimation of iron status. RET-He is a new parameter, equivalent value to CHr, and is easily measurable on the widely spread and popular blood cell counter and is a sensitive and specific marker of iron status in dialysis patients.     

A guide to diagnosis of iron deficiency and iron deficiency anemia in digestive diseases

Iron deficiency （ID）, with or without anemia, is often caused by digestive diseases and should always be investigated, except in very specific situations, as its causes could be serious diseases, such as cancer. Diagnosis of ID is not always easy. Low serum levels of ferritin or transferrin saturation, imply a situation of absolute or functional ID. It is sometimes difficult to differentiate ID anemia from anemia of chronic diseases, which can coexist. In this case, other parameters, such as soluble transferrin receptor activity can be very useful. After an initial evaluation by clinical history, urine analysis, and serological tests for celiac disease, gastroscopy and colonoscopy are the key diagnostic tools for investigating the origin of ID, and will detect the most important and prevalent diseases. If both tests are normal and anemia is not severe, treatment with oral iron can be indicated, along with stopping any treatment with non-steroidal anti-inflammatory drugs. In the absence of response to oral iron, or if the anemia is severe or clinical suspicion of important disease persists, we must insist on diagnostic evaluation. Repeat endoscopic studies should be considered in many cases and if both still show normal results, investigating the small bowel must be considered. The main techniques in this case are capsule endoscopy, followed by     

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.     

Prevalence of iron deficiency anemia and iron deficiency in a pediatric population with inflammatory bowel disease

Objectives: Iron deficiency is the most common cause of anemia in children with inflammatory bowel disease, although the real prevalence is unknown. Intravenous iron is suggested as the first line treatment. This study aims to determine the prevalence of iron deficiency anemia in children with inflammatory bowel disease followed in a Pediatric Gastroenterology Unit of a tertiary center and to evaluate this unit's experience with intravenous iron.

Materials and methods: A retrospective cohort study was designed involving children with inflammatory bowel disease followed in that unit between January 2001 and April 2016. Laboratory results were collected at the moment of diagnosis, after one-year follow-up and prior each IV iron administration performed during the study period. Anemia was defined according to World Health Organization criteria and the iron deficiency was defined using recent guidelines.

Results: Were studied 69 patients 71% had CD and 29% UC. 50.7% were female. Mean patient age at diagnosis was 13.3 years (range 1--17 years). Prevalence of ID and IDA at diagnosis was 76.8% and 43.5%, respectively. After one year follow-up, those values decreased to 68.1% (p?=?.182) and 21.7% (p?=?.002), respectively. Hemoglobin significantly increased (p?<?.001). Intravenous iron was administered to 92.8% of patients. No adverse reactions were reported.

Conclusions: Intravenous iron is the first line in the treatment of Iron deficiency anemia in Inflammatory Bowel disease and it is safe and effective. Persistent anemia and iron deficiency are common.     

Evaluation of reticulocyte haemoglobin content as marker of iron deficiency and predictor of response to intravenous iron in haemodialysis patients

Because serum ferritin and transferrin saturation (TS) have a limitation in estimating iron status in haemodialysis patients, the reticulocyte haemoglobin content (CHr) has been proposed as a new tool. We investigate the accuracy of CHr in comparison with conventional tests and the relationship between changes in CHr and haemoglobin levels after therapy. We selected 140 haemodialysis patients receiving rHuEPO and intravenous iron supplementation and measured their complete blood count, CHr and iron parameters. Iron deficiency was defined as a ferritin <100 microg/l and/or a TS <20%. Hb, CHr, ferritin and TS levels were determined 1 month after therapy. Fifty-three patients were iron deficient. CHr were distributed with 33.7 +/- 1.4 pg in the iron sufficient group and with 29.9 +/- 1.9 pg in the iron deficient group (P = 0.001). The cutoff value of CHr for detecting iron deficiency was <32.4 pg. In iron deficient patients, a significant correlation was found between CHr and TS. The change in CHr after therapy was significantly larger in iron-deficient patients, and a lower baseline CHr is associated with a greater haemoglobin change. CHr is useful in screening iron status in dialysis patients, and a CHr cut-off value of 32 pg is appropriate for the assessment of iron deficiency. Moreover, CHr may serve as a predictor of the response to anaemia treatment.     

Emerging causes of iron deficiency anemia refractory to oral iron supplementation

While oral iron supplementation is commonly used throughout many clinical setting,treatment with intravenous(IV) iron has historically been reserved for specific settings,such as chronic kidney disease,gynecologic issues,and anemia associated with cancer and its treatments.However,the use of IV iron has begun to gain popularity in the treatment of iron deficiency anemia(IDA) associated with two conditions that are being seen more frequently than in years past:patients who are status post gastric bypass procedure and those with inflammatory bowel disease(IBD).The Roux-en-Y procedure involves connecting a gastric pouch to the jejunum,creating a blind loop consisting of distal stomach,duodenum,and proximal jejunum that connects to the Roux limb to form a common tract.IDA occurs in 6%-50% of patients who have undergone a gastric bypass,the etiology being multifactorial.The proximal gastric pouch,the primary site of gastric acid secretion,is bypassed,resulting in a decreased ability to metabolize molecular iron.Once metabolized,most iron is absorbed in the duodenum,which is entirely bypassed.After undergoing bypass procedures,most patients significantly limit their intake of red meat,another factor contributing to post-bypass IDA.Chronic anemia occurs in approximately 1/3 of patients who suffer from IBD,and almost half of all IBD patients are iron deficient.IBD leads to IDA through multiple mechanisms,including chronic intestinal blood loss,decreased absorption capabilities of the duodenum secondary to inflammation,and an inability of many IBD patients to tolerate the side effects of oral ferrous sulfate.In this study,we reviewed the charts of all patients who received IV iron at Sylvester Comprehensive Cancer Center/University of Miami Hospital Clinic from January 2007 to May 2012.The most common indications for IV iron were for issues related to cancer and its treatment(21.9%),IBD(20.1%),and gastric bypass(15.0%).Of the 262 patients who received IV iron,230 received iron sucrose and 36 received iron dextran.While doses of 100,200,300,and 400 mg of iron sucrose were given,100 and 200 mg were by far the most common dosages used,122 and 120 times,respectively.The number of dosages of iron sucrose given ranged from 1 to 46,with a mean of 5.5 and a median of 4 doses.The average dose of iron dextran given was 870.5 mg,with 1000 mg being the most common dosage used.Most patients(22 of 36) who received iron dextran only received one dose.While patients with traditional indications for IV iron,such as gynecologic issues and kidney disease,still were represented in this study,we expect to see a continued increase in physicians using IV iron for emerging gastrointestinal indications,especially considering the increased safety of new low-molecular formulations.     

补充铁剂对上海老年人缺铁性贫血的改善效果

目的观察铁剂纠正老年人缺铁性贫血的效果,为开展老年入缺铁性贫血防治工作提供参考依据。方法招募缺铁性贫血的老年人62例（男性16例,女性46例）,年龄60-79岁,每日口服一包铁营养包（主要成分为焦磷酸铁和富马酸亚铁,含元素铁8mg）,连续服用6个月,分别于干预前、第3个月、第6个月进行贫血相关指标,血清铁蛋白及C反应蛋白测定观察补铁效果,同时进行膳食调查。结果经过6个月干预,老年人血红蛋白水平由112．5g／L上升至114．4g／L,血红蛋白达标率（32．3％）、红细胞计数、平均红细胞浓度、血清铁蛋白达标率（83．9％）基线调查水平差异有统计学意义（P〈0．01）。试验期间老年人能量及有关营养素摄取量差异无统计学意义。结论连续6个月每日补充8mg铁能有效改善老年人缺铁性贫血。     

The role of iron repletion in adult iron deficiency anemia and other diseases

Iron deficiency anemia (IDA) is the most prevalent and treatable form of anemia worldwide. The clinical management of patients with IDA requires a comprehensive understanding of the many etiologies that can lead to iron deficiency including pregnancy, blood loss, renal disease, heavy menstrual bleeding, inflammatory bowel disease, bariatric surgery, or extremely rare genetic disorders. The treatment landscape for many causes of IDA is currently shifting toward more abundant use of intravenous (IV) iron due to its effectiveness and improved formulations that decrease the likelihood of adverse effects. IV iron has found applications beyond treatment of IDA, and there is accruing data about its efficacy in patients with heart failure, restless leg syndrome, fatigue, and prevention of acute mountain sickness. This review provides a framework to diagnose, manage, and treat patients presenting with IDA and discusses other conditions that benefit from iron supplementation.     

幽门螺杆菌感染与缺铁性贫血的关系

目的：探讨幽门螺杆菌(HP)感染与缺铁性贫血(IDA)的关系，以及HP相关IDA的治疗。方法：①分别统计46例IDA伴慢性胃炎与50例非IDA慢性胃炎两组HP感染率。②将42例HP感染相关IDA随机分成两组，分别应用根除细菌加口服铁剂与单用铁剂方案治疗，检测治疗前后血液学指标、观察疗效。结果：IDA伴慢性胃炎者HP感染率高于非IDA慢性胃炎者，两者差异有统计学意义；HP感染相关IDA患者接受根除细菌加铁剂治疗前后其Hb、血清铁、铁蛋白均显著增高，而单用铁剂组治疗前后血液学指标无显著变化。结论：HP感染与IDA可能有一定相关性，当IDA患者铁剂治疗效果不显著时宜考虑是否存在HP相关IDA．根除HP感染后对IDA有一定治疗作用。     

Patients with iron deficiency anemia have an increased prevalence of gallstones

We determined the frequency of gallstones (GS) in iron deficiency anemia (IDA) patients and evaluated factors that could affect GS formation—like lipid levels and gallbladder (GB) motilities of the patients. One hundred and eleven IDA patients (88 females, 23 males; median age, 42) and 81 healthy controls (68 females, 13 males; median age, 42) were included into our study. The clinical findings of all IDA patients were recorded down; biochemical values and body mass index (BMI) were determined; and abdominal ultrasonography was performed. In addition, GB emptying was monitored by ultrasound at 30-min intervals for 2 h after a mixed meal in randomly chosen, age-matched 25 IDA patients and 26 controls. Fasting volume (FV), residual volume (RV), and ejection fraction (EF) for all GBs were determined. The frequency of GS plus cholecystectomy was significantly higher in IDA patients (15 cases, 13.5%) than in the control group (five cases, 6.2%, p = 0.048). IDA patients with GS plus cholecystectomy were older than those without GS plus cholecystectomy (p < 0.001). FV and EF did not differ between IDA and control groups (p > 0.05). On the other hand, RV was significantly higher in IDA group than in controls (p = 0.035). The frequency of GS in IDA patients was significantly higher than in controls. The increased prevalence of GS in IDA might be explained with impaired GB motility.     

Δ‐CHr improves the identification of anemic syndromes and the evaluation of hemoglobin synthesis

Reticulocyte hemoglobin content (CHr) is considered an index of iron status, helpful in the differential diagnosis of microcytoses. Its potential can be enhanced by comparing CHr dynamic reference values (CHr‐e: expected CHr), which are proportional to the MCVr variations occurring in micro‐ or macrocytosis, with measured CHr values. We demonstrate that the difference between measured CHr and CHr‐e (ΔCHr) is helpful to differentiate the anemic syndromes and, in particular, β‐talassemia vs. presumable sideropenia. ΔCHr can also indicate when to interrupt iron supplementation. ΔCHr allows an insight into the erythropoiesis of thalassemic and sideropenic subjects, pointing out the reduced hemoglobin production and ineffective erythroid activity in these conditions.     

High serum transferrin receptor level in anemia of chronic disorders indicates coexistent iron deficiency

Blood transferrin receptor (TR) level is largely determined by the quantum of erythropoiesis and by intracellular iron content of the cells of the erythroid lineage. Hence, a high serum TR level has been found to be useful in distinguishing iron deficiency anemia (IDA) from anemia of chronic disorders (ACD). In order to examine its potential role in the diagnosis of concomitant iron deficiency in ACD, we determined serum TR levels in 130 cases of ACD, in 25 cases of IDA, and in 40 normal adults. As expected, all patients of IDA had significantly higher serum TR levels compared to the normal subjects (4.2-19.2 microg/dL vs. 1.3-3.0 microg/dL) (P < 0.002). In 11/25 cases of IDA, the total iron-binding capacity (TIBC) was in the normal range although bone marrow iron store was absent and serum TR levels were high, thereby highlighting the superiority of TR level in the diagnosis of iron deficiency compared to TIBC. Although 54% (70/130) patients of ACD had normal or low serum TR levels (0.9-3.0 microg/dL) as expected, in 46% (60/130) of ACD patients, serum TR levels were high (3.2-11.0 microg/dL). Mean corpuscular volume, red cell distribution width, and transferrin saturation were significantly lower (P < 0.001) in the latter group of patients compared to the former, and these parameters resembled those in IDA patients. Also, serum iron was lower and TIBC was higher in this group of ACD patients compared to those with normal or low serum TR. All these features point to an "IDA-like" profile of ACD patients with high TR and support the possibility of co-existent iron deficiency in this subgroup of ACD patients. In light of these observations it would be prudent to treat ACD patients with high serum TR levels with iron replacement therapy.