Iron deficiency and anaemia in pregnancy: modern aspects of diagnosis and therapy

The prevalence of iron-deficiency anemia in different regions of the world ranges from 12 to 43%. The increased iron requirement in pregnancy and the puerperium carry with it an increased susceptibility to iron deficiency and iron-deficiency anemia and perioperative or peripartal blood transfusion. Prevention and correction presuppose reliable laboratory parameters and a thorough understanding of the mechanisms of iron therapy. The Hb level alone is insufficient to guide management. A complete work-up (ferritin, transferrin saturation) is essential, preferably with hematological indices such as hypochromic and microcytic red cells and reticulocytes, classified by degree of maturity, in particular, before parenteral therapy is given. Since ferritin acts as both an iron-storage and acute-phase protein, it cannot be used to evaluate iron status in the presence of inflammation. A high ferritin level thus requires the presence of an inflammatory process to be eliminated before it can be taken at face value. If the C-reactive protein level is also raised, the soluble TfR concentration can be used, since it is unaffected by inflammation. Inadequate understanding of the complex chemistry of parenteral iron administration was previously responsible for serious side effects, such as toxic and allergic reactions, and even anaphylactic shock, in particular with dextran preparations. However, the current type II iron complexes that release iron to the endogenous iron-binding proteins with a half-life of about 6 hours are not only effective but carry a minimal risk of allergic accident and overload, especially after a comprehensive pretreatment work-up. Our departmental data collected over 8 years and backed by postmarketing experience in 25 countries indicate that iron sucrose complex therapy is a valid first-line option for the safe and rapid reversal of iron-deficiency anemia.     

Iron deficiency anaemia revisited

Iron deficiency anaemia is a global health concern affecting children, women and the elderly, whilst also being a common comorbidity in multiple medical conditions. The aetiology is variable and attributed to several risk factors decreasing iron intake and absorption or increasing demand and loss, with multiple aetiologies often coexisting in an individual patient. Although presenting symptoms may be nonspecific, there is emerging evidence on the detrimental effects of iron deficiency anaemia on clinical outcomes across several medical conditions. Increased awareness about the consequences and prevalence of iron deficiency anaemia can aid early detection and management. Diagnosis can be easily made by measurement of haemoglobin and serum ferritin levels, whilst in chronic inflammatory conditions, diagnosis may be more challenging and necessitates consideration of higher serum ferritin thresholds and evaluation of transferrin saturation. Oral and intravenous formulations of iron supplementation are available, and several patient and disease‐related factors need to be considered before management decisions are made. This review provides recent updates and guidance on the diagnosis and management of iron deficiency anaemia in multiple clinical settings.     

Iron deficiency: a concise review

Iron deficiency is a major worldwide health problem. There is recent evidence that the anemia is only the last manifestation of the syndrome and that symptoms occur before the anemia is manifest. Advances in outlining the physiology of iron deficiency have been made, gaps remain in the current understanding. While oral iron supplement remains the mainstay, some indications for the intravenous administration have developed. This review will highlight the epidemiology, physiology, clinical presentation, and treatment options.     

Iron deficiency anaemia in young women

OBJECTIVES: The expression density of GPIaIIa, the primary platelet collagen receptor (integrin alpha2beta1), is linked to two polymorphisms (GPIa-807C/T and HPA-5a/b). During evolution a gene shift from the genotypes GPIa-807CC-HPA-5bb to the genotypes GPIa-807CT-HPA-5aa has taken place. The aim of the study was to assess whether iron deficiency anaemia (e.g. increased blood loss) in young women could be associated with a specific genotype, indicating a role as potential evolutionary selection factor. STUDY DESIGN: Women between 18 and 40 yr of age presenting for their first blood donation were asked about alimentary habits and use of oral contraception. Haemoglobin and serum ferritin were measured and the GPIa-C807T and HPA-5 genotypes were determined. RESULTS: Two hundred women were included and grouped according to the WHO definition for iron deficiency anaemia (haemoglobin <121 g L(-1) and ferritin <15 microg L(-1)). Eight women fulfilled both WHO-criteria for iron deficiency anaemia, 145 women fulfilled none. No differences regarding age, use of oral contraceptives, alimentary habits, and HPA-5 were found between the groups. The GPIa-807CC genotype was strongly over-represented in the WHO-anaemic women as compared to the non-WHO-anaemic women (87.5% vs. 33.1%, P=0.003). CONCLUSION: Iron deficiency anaemia in young women might have been the evolutionary disadvantage causing the gene shift from GPIa-807CC to 807CT.     

Iron deficiency: definition and diagnosis

There has been a continuous refinement over the past several decades of methods to detect iron deficiency and assess its magnitude. The optimal combination of measurements differs for clinical and epidemiological assessment. Clinically, the major problem is to distinguish true iron deficiency from other causes of iron-deficient erythropoiesis, such as the anaemia of chronic disease. Epidemiologically, techniques that provide quantified estimates of body iron are preferable. For both purposes, the serum ferritin is the focal point of the laboratory detection of iron deficiency. Serum ferritin measurements provide a reliable index of body iron stores in healthy individuals, a cost-effective method of screening for iron deficiency, and a useful alternative to bone marrow examinations in the evaluation of anaemic patients. Preliminary studies indicate that measurement of the serum transferrin receptor may be the most reliable way to assess deficits in tissue iron supply.     

Practical gastrointestinal investigation of iron deficiency anaemia

Introduction: About 10% of oesophagogastroduodenoscopies (OGDs) and colonoscopies are done for investigation of iron deficiency anemia (IDA) . Much of the existing guidance on investigation of IDA predates CRC screening, which has driven significant improvements in colonoscopy quality and completion rates, as well as a reduction in Helicobacter pylori prevalence and increase in PPI usage, and therefore probably needs re-consideration. New investigations, e.g. CT colonography, enteroscopy and capsule endoscopy have also been introduced.

Areas covered: This review updates the approach to practical investigation of IDA. Medline was searched using the terms iron deficiency AND anemia AND/OR gastroscopy, colonoscopy, capsule and enteroscopy, together with review of recent relevant published abstracts on the topic.

Expert commentary: Gastrointestinal pathology is now a more common cause of IDA than upper GI causes, reflecting better colonoscopy accuracy and completion rates as well as changing disease patterns, and carcinomas are more likely cause IDA than benign adenomas. Increasing use of antiplatelet and anticoagulants is driving greater presentation of IDA. Capsule endoscopy, enteroscopy and CT colonography are increasingly used. Fecal occult blood testing may be a useful simple screening method in the frail, as a negative test can avoid the need for invasive tests.     

Iron deficiency across chronic inflammatory conditions: International expert opinion on definition,diagnosis, and management

Iron deficiency, even in the absence of anemia, can be debilitating, and exacerbate any underlying chronic disease, leading to increased morbidity and mortality. Iron deficiency is frequently concomitant with chronic inflammatory disease; however, iron deficiency treatment is often overlooked, partially due to the heterogeneity among clinical practice guidelines. In the absence of consistent guidance across chronic heart failure, chronic kidney disease and inflammatory bowel disease, we provide practical recommendations for iron deficiency to treating physicians: definition, diagnosis, and disease‐specific diagnostic algorithms. These recommendations should facilitate appropriate diagnosis and treatment of iron deficiency to improve quality of life and clinical outcomes.     

Iron deficiency and thrombosis: literature review.

Compared to primary thrombocytosis such as that caused by essential thrombocytosis, reactive thrombocytosis is generally regarded as benign. However, reactive thrombocytosis has infrequently been reported to cause severe and even fatal complications. Two fatal cases of reactive thrombocytosis and iron deficiency anemia associated with peripheral/pulmonary vascular and cerebrovascular thrombosis are described. The literature on thrombosis and reactive thrombocytosis associated with iron deficiency anemia is reviewed.     

Iron deficiency: From diagnosis to treatment

Iron deficiency is the most frequent cause of anaemia worldwide. It impairs quality of life, increases asthenia and can lead to clinical worsening of patients. In addition, iron deficiency has a complex mechanism whose pathologic pathway is recently becoming better understood. The discovery of hepcidin has allowed a better clarification of iron metabolism regulation. Furthermore, the ratio of concentration of soluble transferrin receptor to the log of the ferritin level, has been developed as a tool to detect iron deficiency in most situations. The cause of iron deficiency should always be sought because the underlying condition can be serious. This review will summarize the current knowledge regarding diagnostic algorithms for iron deficiency anaemia. The majority of aetiologies occur in the digestive tract, in men and postmenopausal women, and justify morphological examination of the gut. First line investigations are upper gastrointestinal endoscopy and colonoscopy, and when negative, the small bowel should be explored; newer tools such as video capsule endoscopy have also been developed. The treatment of iron deficiency is aetiological if possible and iron supplementation whether in oral or in parenteral form. New parenteral formulations are available and seem to have promising results in terms of efficacy and safety.     

Iron deficiency anaemia and ‘normal’ bone marrow haemosiderin

Summary During a survey of patients with epithelial symptoms, pica and restless legs an apparently normal amount of stainable iron was found in the bone marrow of four women with chronic iron deficiency anaemia. They all had previously been treated with different parenteral iron preparations. No massive iron dextran infusion had been given. The diagnosis of iron deficiency was confirmed by a positive response to iron therapy. There was no indication that these iron complexes which were slowly utilized (if at all) had any harmful effects. The finding is primarily important from a diagnostic point of view.

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Zusammenfassung Bei der Durchsicht eines Patientenmaterials mit epithelialen Symptomen, Phagomania compulsiva (pica) und restless legs fand man bei vier weiblichen Patienten mit chronischer Eisenmangelanämie offenbar normale Mengen anfärbbaren Eisens im Knochenmark. Sie waren früher alle mit verschiedenen parenteralen Eisenpräparaten behandelt worden. Es waren keine größeren Mengen Eisen-Dextran infundiert worden. Die Diagnose Eisenmangel wurde durch die positive Reaktion auf Behandlung mit Eisen bestätigt. Es ergab sich kein Anhalt dafür, daß diese Eisenkomplexe, die langsam (wenn überhaupt) verwertet werden, irgendwelche schädlichen Wirkungen zeigen. Der Befund hat in erster Linie diagnostische Bedeutung.

     

Iron deficiency in childhood and adolescence: retrospective review

Two hundred and thirty-eight subjects of both sexes, age range 7.5 months-16 years, with iron deficiency (ID), were included in a retrospective review of ID causes, to determine the best treatment. Inadequate iron intake was the cause of ID or iron deficiency anemia (IDA) in 59 subjects from the first months of life to adolescence. Blood loss linked to cow's milk intolerance was the cause of ID or IDA in 37 younger children. Meckel's diverticulum (MD) (6 cases), reflux esophagitis (RE) (10 cases), some drugs such as acetyl salicylic acid (11 cases) induced bleeding with ID or IDA in children and adolescents. In pubertal females with ID or IDA, polymenorrhea was observed in 16 cases. Coelic disease (CD) (37 cases), Helicobacter pylori infection (HPI) (39 cases), association of HPI and CD (8 cases), enteromonas infection (15 cases), determining particularly malabsorption, were causes of ID or IDA in patients of a wide age range, unresponsive to iron therapy. Our findings show that iron replacement therapy was not always required and should not be prescribed until the diagnosis is certain.