Management of iron-deficiency anemia following acute gastrointestinal hemorrhage: A narrative analysis and review

Many patients experiencing acute gastrointestinal bleeding (GIB) require iron supplementation to treat subsequent iron deficiency (ID) or iron-deficiency anemia (IDA). Guidelines regarding management of these patients are lacking. We aimed to identify areas of unmet need in patients with ID/IDA following acute GIB in terms of patient management and physician guidance. We formed an international working group of gastroenterologists to conduct a narrative review based on PubMed and EMBASE database searches (from January 2000 to February 2021), integrated with observations from our own clinical experience. Published data on this subject are limited and disparate, and those relating to post-discharge outcomes, such as persistent anemia and re-hospitalization, are particularly lacking. Often, there is no post-discharge follow-up of these patients by a gastroenterologist. Acute GIB-related ID/IDA, however, is a prevalent condition both at the time of hospital admission and at hospital discharge and is likely underdiagnosed and undertreated. Despite limited data, there appears to be notable variation in the prescribing of intravenous (IV)/oral iron regimens. There is also some evidence suggesting that, compared with oral iron, IV iron may restore iron levels faster following acute GIB, have a better tolerability profile, and be more beneficial in terms of quality of life. Gaps in patient care exist in the management of acute GIB-related ID/IDA, yet further data from large population-based studies are needed to confirm this. We advocate the formulation of evidence-based guidance on the use of iron therapies in these patients, aiding a more standardized best-practice approach to patient care.     

A prospective study of same day bi-directional endoscopy in the evaluation of patients with occult gastrointestinal bleeding

Objective. Previous studies show conflicting results in the diagnostic yield of oesophagogastroduodenoscopy (OGD) and colonoscopy (bi-directional) in identifying potential bleeding sources (PBS) in patients investigated for occult gastrointestinal bleeding (OGIB). The aims of this study were to evaluate the diagnostic yield of bi-directional endoscopy in patients presenting with OGIB and to assess the factors predictive of a positive yield. Material and methods. Patients with OGIB referred to the gastroenterology unit were prospectively included in the study. Colonoscopy was immediately followed by OGD. Predetermined criteria for the diagnosis of a PBS were used. Potential clinical factors predictive of positive yield were assessed. Results. Of the 219 patients (mean age 65 years, 34% M), 110 (50%) had at least one PBS. Colonoscopy revealed 87 PBS in 73 patients (33%), the most common being adenoma. OGD detected 49 PBS in 48 patients (22%), gastric ulcer being the most common. Of the patients with PBS at OGD, 23% also had a PBS at colonoscopy, including 3 patients with colonic cancers. Patients presenting with either a positive faecal occult blood test (FOBT) or iron-deficiency anaemia (IDA) only had a significantly lower yield for PBS than patients with combined positive FOBT and IDA. The percentages of patients with a PBS increased substantially with age. Conclusions. A PBS was found in only 50% of the patients. Colonoscopy had a slightly higher diagnostic yield, and as expected, resulted in a significantly higher cancer detection rate than OGD. In older patients, colonoscopy should be done irrespective of the findings at OGD. Gastrointestinal-specific symptoms and the use of ASA/NSAIDs were not predictive in finding or localizing PBS.     

The severity of anemia does not correlate with the risk of gastrointestinal cancer in subsequent evaluation

Abstract

Introduction: Iron deficiency anemia (IDA) is a risk factor for gastrointestinal (GI) malignancies. Little is known regarding the correlation between the depth of anemia and the risk for GI malignancy. The aim of this study was to test the hypothesis that very low hemoglobin levels pose an additional risk compared to low hemoglobin levels.

Methods: Patients 40–70?years old, presenting to the ER with IDA during years 2016–2017 were retrospectively analyzed. Comparison was performed between two groups, one with a very low hemoglobin level (below 8?g/dL) and the other a low hemoglobin level (between 8–10?g/dL).

Results: 1020 patients were analyzed, and 107 fulfilled the inclusion criteria. Seventy-five patients (70%) were in the very low hemoglobin group and 21 patients (19.6%) were diagnosed with a new GI malignancy. Mean age was 56, 49 (45%) were females, and 68 (63%) underwent esophagogastroduodenoscopy (EGD) or/and colonoscopy during the index hospitalization. The median hemoglobin and MCV were 7.3?G/dL, and 73?fL, respectively. New malignancies were found in 15/75 (20%) and 6/32 (19%) of patients with very low and low hemoglobin levels, respectively (p?=?.88). GI malignancies were more commonly found in females compared to males, 14 (29%) vs. 7 (12%), p?=?.032, respectively. The right colon was the most common site for malignancy. Active GI bleeding was not a risk factor for GI malignancy.

Conclusions: Very low hemoglobin levels and overt GI bleeding do not pose an additional risk factor for GI malignancy, compared to low hemoglobin levels and no overt GI bleeding.     

Kidney injury in infants and children with iron-deficiency anemia before and after iron treatment

Background: Our study aimed to investigate the effects of iron-deficiency anemia (IDA) on renal tubular functions before and after iron treatment for infants and children with IDA. We measured urinary levels of two kidney injury markers: neutrophil gelatinase-associated lipocalin (NGAL) and liver-type fatty acid-binding protein (L-FABP).

Material and methods: Thirty-six infants and children with IDA and 20 matched healthy controls were included. We assessed different laboratory parameters, estimated glomerular filtration rate, urinary levels of NGAL, and L-FABP. Urinary kidney injury markers were measured in IDA patients before and after 3 months of oral iron therapy.

Results: IDA patients had significantly higher urinary NGAL and L-FABP levels compared to their healthy controls. After 3 months of oral iron treatment, there was a significant improvement (decrease) in urinary NGAL and L-FABP in infants and children with IDA. Urinary markers returned to normal levels (healthy control levels) in children with IDA, but not for infants with IDA compared to their healthy controls.

Conclusion: Subclinical kidney injury was found in infants and children with IDA. This injury was completely reversible in older children with IDA and partially reversible in infants with IDA after iron therapy. Higher urinary levels of kidney injury molecules in IDA infants after iron treatment are suggestive of more sensitivity of these infants to oxidative stress caused by iron therapy or may be due to the immaturity of the kidney and more damage caused by IDA which may require more time to recover.     

胶囊内镜下小肠黏膜特征分析53例

目的:回顾性分析胶囊内镜检查患者53例,认识胶囊内镜下小肠正常黏膜特征及小肠病变黏膜特征.方法:2010-08/2011-08,利用Miro Cam胶囊内镜系统对患者53例行胶囊内镜检查.统计患者的年龄、性别、症状、体征等临床资料,将受检者分为不明原因的消化系出血,疑为功能性胃肠病,腹痛、腹泻、腹胀,便秘,体检等共5组;通过查阅病案及电话回访,搜集资料,将胶囊内镜下所见作出最终的临床诊断;分析胶囊内镜下小肠正常及病变黏膜特征.结果:在53例患者中,1例因吞服胶囊后无图像信号,未能顺利完成胶囊内镜检查;1例因患者吞咽胶囊困难而无法进行;其余51例均顺利到达结肠,到达结肠率为96.22%.胃的平均运行时间为69.78 min,小肠的平均运行时间为513.25 min.48例有消化系疾病的阳性结果,3例未见异常,阳性率为90.57%.在所有疑诊小肠疾病的51例患者中,胶囊内镜小肠病变总的诊断率为92.15%(47/51);空肠及回肠阳性诊断率为52.94%,包括炎症12例(1例临床确诊为Crohn’s病),息肉3例,不明肿块3例,淋巴滤泡增生1例,疑似小肠淋巴管扩张7例,钩虫病1例;同时检出反流性食管炎1例;慢性胃炎26例,糜烂性胃炎7例,胃部息肉3例;结肠炎症3例,结肠息肉5例,大肠黑变病2例.胶囊均自然排出体外,无梗阻等并发症的发生.结论:Miro Cam胶囊内镜是一种非侵入性的检查手段,检查安全,顺应性好;在胶囊内镜下,正常小肠黏膜及病变黏膜均呈现出一定的特征.     

Are repeat upper gastrointestinal endoscopy and colonoscopy necessary within six months of capsule endoscopy in patients with obscure gastrointestinal bleeding?

Background and Aim: Medicare reimbursement for capsule endoscopy for the investigation of obscure gastrointestinal bleeding in Australia requires endoscopy and colonoscopy to have been performed within 6 months. This study aims to determine the diagnostic yield of repeating these procedures when they had been non‐diagnostic more than 6 months earlier. Methods: Of 198 consecutive patients who were referred for the investigation of obscure gastrointestinal bleeding, 50 underwent repeat endoscopy and colonoscopy solely to enable reimbursement (35 females and 15 males; mean age 59.4 [range: 21–82] years). The average duration of obscure bleeding was 50.16 (range: 9–214) months. The mean number of prior endoscopies was 3 (median: 2) and 2.8 colonoscopies (median: 2). The most recent endoscopy had been performed 18.9 (median: 14; range: 7–56) months, and for colonoscopy, 19.1 (median 14; range 8‐51) months earlier. Results: A probable cause of bleeding was found at endoscopy in two patients: gastric antral vascular ectasia (1) and benign gastric ulcer (1). Colonoscopy did not reveal a source of bleeding in any patient. Capsule endoscopy was performed in 47 patients. Twenty four (51%) had a probable bleeding source identified, and another five (11%) a possible source. These included angioectasia (17 patients), mass lesion (2), non‐steroidal anti‐inflammatory drug enteropathy (2), Cameron's erosions (2), and Crohn's disease (1). Four patients undergoing repeat capsule endoscopy had a probable bleeding source detected. Conclusion: The yield of repeat endoscopy and colonoscopy immediately prior to capsule endoscopy is low when these procedures have previously been non‐diagnostic. Such an approach is also not cost‐effective.     

Lactoferrin sequestration and its contribution to iron-deficiency anemia in Helicobacter pylori-infected gastric mucosa

BACKGROUND AND AIM: It is known that lactoferrin serves as a source of iron for Helicobacter pylori in gastric mucosa. The present study was undertaken to investigate the relationship between lactoferrin and H. pylori infection coexistent with iron-deficiency anemia by determining the lactoferrin levels in gastric biopsy specimens, and by locating the major sites of lactoferrin expression, according to the presence or absence of iron-deficiency anemia. METHODS: One hundred and one adolescents who underwent gastroduodenoscopy were divided into four groups: controls without H. pylori infection (NL; n =43); patients with H. pylori infection (HP; n = 26); patients with iron-deficiency anemia (IDA; n = 6); and patients with H. pylori gastritis and coexisting iron-deficiency anemia (HPIDA; n = 26). The gastric mucosal levels of lactoferrin were measured by immunoassay. Immunohistochemical technique was used to allow identification of the location and quantification of the lactoferrin expression. RESULTS: The mucosal level of lactoferrin was highest (3.93 +/- 2.73 ng/microg protein) in HPIDA, followed by 2.67 +/- 1.79 ng/microg protein in HP, 0.59 +/- 0.57 ng/microg protein in NL and 0.14 +/- 0.10 ng/microg protein in IDA. Their multiple comparisons were statistically significant at the 0.05 level. After the eradication of H. pylori in 12 HPIDA patients who underwent follow-up endoscopy, the mean mucosal level of lactoferrin decreased significantly, while the blood hemoglobin level correspondingly increased. The major sites of lactoferrin expression by immunohistochemistry were in glands and neutrophils within epithelium. Lactoferrin was stained weakly in NL and IDA, and strongly in HP and HPIDA. CONCLUSION: The lactoferrin sequestration in the gastric mucosa of HPIDA was remarkable, and this finding seems to give a clue that leads to the clarification of the mechanism by which H. pylori infection contributes to iron-deficiency anemia.     

Single-center experience of 309 consecutive patients with obscure gastrointestinal bleeding

AIM: To investigate the diagnostic yield of capsule endoscopy (CE) in patients with obscure gastrointestinal bleeding (OGIB), and to determine whether the yield was affected by different bleeding status.METHODS: Three hundred and nine consecutive patients (all with recent negative gastric and colonic endoscopy results) were investigated with CE; 49 cases with massive bleeding and 260 cases with chronic recurrent overt bleeding. Data regarding OGIB were obtained by retrospective chart review and review of an internal database of CE findings.RESULTS: Visualization of the entire small intestine was achieved in 81.88% (253/309) of cases. Clinically positive findings occurred in 53.72% (166/309) of cases. The positivity of the massive bleeding group was slightly higher than that of the chronic recurrent overt bleeding group but there was no significant difference (59.18% vs 52.69%, P > 0.05) between the two groups. Small intestinal tumors were the most common finding in the entire cohort, these accounted for 30% of clinically significant lesions. In the chronic recurrent overt bleeding group angioectasia incidence reached more than 29%, while in the massive bleeding group, small intestinal tumors were the most common finding at an incidence of over 51%. Increasing patient age was associated with positive diagnostic yield of CE and the findings of OGIB were different according to age range. Four cases were compromised due to the capsule remaining in the stomach during the entire test, and another patient underwent emergency surgery for massive bleeding. Therefore, the complication rate was 1.3%. CONCLUSION: In this study CE was proven to be a safe, comfortable, and effective procedure, with a high rate of accuracy for diagnosing OGIB.     

C-reactive protein for simple prediction of mortality in patients with acute non-variceal upper gastrointestinal bleeding: A retrospective analysis

In upper gastrointestinal bleeding (UGIB), scoring systems using multiple variables were developed to predict patient outcomes. We evaluated serum C-reactive protein (CRP) for simple prediction of patient mortality after acute non-variceal UGIB.The associated factors for 30-day mortality was investigated by regression analysis in patients with acute non-variceal UGIB (N = 1232). The area under the receiver operating characteristics (AUROC) curve was analyzed with serum CRP in these patients and a prospective cohort (N = 435). The discriminant validity of serum CRP was compared to other prognostic scoring systems by means of AUROC curve analysis.Serum CRP was significantly higher in the expired than survived patients (median, 4.53 vs 0.49; P < .001). The odds ratio of serum CRP was 4.18 (2.10–9.27) in multivariate analysis. The odds ratio of high serum CRP was higher than Rockall score (4.15 vs 1.29), AIMS65 (3.55 vs 1.71) and Glasgow-Blatchford score (4.32 vs 1.08) in multivariate analyses. The AUROC of serum CRP at bleeding was 0.78 for 30-day mortality (P < .001). In the validation set, serum CRP was also significantly higher in the expired than survived patients, of which AUROC was 0.73 (P < .001). In predicting 30-day mortality, the AUROC with serum CRP was not inferior to that of other scoring systems.Serum CRP at bleeding can be simply used to identify the patients with high mortality after acute non-variceal UGIB.     

影响胶囊内镜诊断不明原因消化道出血因素的分析

目的为提高胶囊内镜诊断不明原因消化道出血的诊断率,探讨影响胶囊内镜诊断不明原因消化道诊断率的因素。方法胶囊内镜检查172例,其中不明原因的消化道出血的患者61例,分为2组,A组为胶囊内镜检查明确出血病变者,B组为无明确出血病变者,根据年龄、性别、病史、病变程度、病变表现、排空时间、肠道清洁、检出率、诊断率等对比分析。结果消化道出血的检出率为88．52％,包括胃炎、肠炎、血管畸形、肠息肉、食管静脉曲张等。出血的诊断率为67．2％,包括小肠糜烂,克罗恩病、糜烂性胃炎、溃疡病、肿瘤等。两组病人年龄、性别比较无明显差异,A组病史活动性出血者多,病史长,合并症多,小肠转运时间较长,肠道清洁好,病变程度重,病变检出率高。结论注意病人的选择、合理的小肠转运时间、肠道清洁好、了解出血原因和排序、提高病变鉴别、图像解读及临床综合判断和随访等,可以提高胶囊内镜检查的诊断率,使不明原因消化道出血病变得到及时明确的处理。     

10 years of capsule endoscopy: an update

Capsule endoscopy (CE) has evolved in a few short years to become a first-line, noninvasive diagnostic technique for the small bowel. CE is now being utilized worldwide to assess patients for obscure gastrointestinal bleeding, possible Crohn’s disease, celiac disease and small bowel tumors. The device is now used in tandem with balloon enteroscopy to direct therapeutic interventions. Alterations and improvements in CE have also led to the evaluation of both the esophagus and colon. It can be anticipated that in the near future pan CE of the entire GI tract will be performed, as well as possible tissue acquisition, drug delivery and therapeutic interventions.     

A prospective, single-blind trial comparing wireless capsule endoscopy and double-balloon enteroscopy in patients with obscure gastrointestinal bleeding

BACKGROUND: Wireless capsule endoscopy (CE) and double-balloon enteroscopy (DBE) are new methods enabling diagnostic endoscopy of the entire small intestine. However, which of the two is superior is unclear. We therefore prospectively compared the clinical efficacy of CE and DBE. METHODS: We prospectively examined 32 patients with obscure gastrointestinal bleeding. CE preceded DBE by 1-7 days, and all patients underwent DBE twice, by antegrade and retrograde approaches, to evaluate the entire small intestine. Physicians evaluating the results of CE and DBE were blind to the results of the other method. We evaluated diagnosis, diagnostic yield of the two methods, and clinical outcomes. RESULTS: CE revealed abnormal findings in 29 (90.6%) of 32 patients. CE definitively or probably detected the sources of bleeding in 23 (71.9%) of the 32 patients, including angioectasias (eight), erosions (seven), ulcers (five), tumor (one), and hemorrhagic polyps (two). DBE definitely or probably detected the sources of bleeding in 21 (65.6%) of the 32 patients, including angioectasias (seven), erosions (four), ulcers (five), tumor (one), hemorrhagic polyps (two) and diverticula (two). CE yielded more abnormal findings than DBE (CE 90.6%, DBE 65.6%) (P = 0.032), although there were no significant differences in diagnostic yield between the methods. We were able to perform additional treatment or biopsy with DBE in 13 patients, including coagulation therapy (ten), endoscopic mucosal resection (one), biopsy (seven), and extraction of retained CE (two). CONCLUSIONS: Our results demonstrate the superiority of CE in detecting abnormal lesions, and the superiority of DBE in endoscopic management.     

Diagnostic yield of dual-phase computed tomography enterography in patients with obscure gastrointestinal bleeding and a non-diagnostic capsule endoscopy

Background and Aim: In patients with obscure gastrointestinal (GI) bleeding, capsule endoscopy is widely used to determine the source of bleeding. However, there is currently no consensus on how to further evaluate patients with obscure GI bleeding with a non‐diagnostic capsule endoscopy examination. This study aims to determine the diagnostic yield of dual‐phase computed tomographic enterography (CTE) in patients with obscure GI bleeding and a non‐diagnostic capsule endoscopy. Methods: Patients with obscure GI bleeding who were referred for capsule endoscopy were prospectively enrolled. Obscure GI bleeding was defined as overt if there was obvious GI bleeding; otherwise it was defined as occult. Patients with a non‐diagnostic capsule endoscopy and no contraindications underwent a CTE. Results: Capsule endoscopy was performed in 52 patients; 26 patients (50%) had occult GI bleeding and 26 patients (50%) had overt GI bleeding. CTE was then performed in 25 of the 48 patients without a definitive source of bleeding seen on capsule endoscopy. The diagnostic yield of CTE was 0% (0/11) in patients with occult bleeding versus 50% (7/14) in patients with overt bleeding (P < 0.01). Using clinical follow up as the gold standard, for the 25 patients with a non‐diagnostic capsule, CTE had a sensitivity of 33% (95% confidence interval 0.15, 0.56) and a specificity of 75% (95% confidence interval 0.22, 0.99). Conclusions: In patients with a non‐diagnostic capsule endoscopy examination, CTE is useful for detecting a source of GI bleeding in patients with overt, but not occult, obscure GI bleeding.     

胶囊内镜在小肠疾病诊断中的作用

目的:小肠疾病很难诊断,现有的诊断技术又不尽如人意,而胶囊内镜能发现整个小肠内的微小病变。为此,我们对胶囊内镜在小肠疾病诊断中的价值进行评估。方法:自2002年5月至2003年9月,我们对经结肠镜、胃镜、X线钡餐造影、小肠钡灌造影、血管造影或核素扫描等检查未发现异常的79例疑患小肠疾病、尤其是不明原因消化道出血的患者,进行胶囊内镜检查,其中不明原因的消化道出血患者56例。结果:75例完成最终研究。75例患者中经胶囊内镜检查共发现异常63例,检出率为84％;其中能明确解释临床病因者50例,诊断率为66.6％,包括消化道血管病变21例、小肠炎症性肠病16例、小肠息肉5例、小肠恶性间质肿瘤2例、小肠类癌1例(该患者同时伴升结肠脂肪瘤)、淋巴瘤1例、粘膜下肿瘤3例及憩室1例。所获取的图像质量良好。结论:胶囊内镜对小肠疾病尤其是不明原因消化道出血具有良好的诊断价值。     

单气囊小肠镜对不明原因消化道出血的诊治价值

目的评价单气囊小肠镜对不明原因消化道出血的诊治价值及安全性。方法 2009年6月-2011年12月共有60例不明原因消化道出血患者进行单气囊小肠镜检查。结果 60例接受单气囊小肠镜检查患者中53例有阳性发现,发现阳性病变55处,阳性诊断率为88.33%。所有患者均顺利完成检查,未发生出血、穿孔等严重并发症,也未出现麻醉并发症或麻醉意外。结论单气囊电子小肠镜对不明原因消化道出血具有较高病变检出率和病因诊断准确率,是一种安全、可靠的检查手段。     

Occult and obscure gastrointestinal bleeding: Causes and diagnostic approach in 2009

Gastrointestinal bleeding can be obscure or occult (OGIB), the causes and diagnostic approach will be discussed in this editorial. The evaluation of OGIB consists on a judicious search of the cause of bleeding, which should be guided by the clinical history and physical findings. The standard approach to patients with OGIB is to directly evaluate the gastrointestinal tract by endoscopy, abdominal computed tomography, angiography, radionuclide scanning, capsule endoscopy. The source of OGIB can be identified in 85%-90%, no bleeding sites will be found in about 5%-10% of cases. Even if the bleedings originating from the small bowel are not frequent in clinical practice (7.6% of all digestive haemorrhages, in our casuistry), they are notoriously difficult to diagnose. In spite of progress, however, a number of OGIB still remain problematic to deal with at present in the clinical context due to both the difficulty in exactly identifying the site and nature of the underlying source and the difficulty in applying affective and durable diagnostic approaches so no single technique has emerged as the most efficient way to evaluate OGIB.