Interpreting iron studies

Abstract

A 63 year old woman visits her doctor with a three month history of fatigue and generalised joint pains. Her medical history is unremarkable and she reports no recent stress, infection, or weight loss. There are no abnormalities on clinical examination. Haemoglobin, creatinine, and electrolytes, liver enzymes, glucose, inflammatory markers, and thyroid function tests are normal. Ferritin, iron, transferrin, and transferrin saturation are also requested.This article discusses some situations in which ferritin and iron studies might be helpful and how to avoid common pitfalls in their interpretation. What are the next investigations?The doctor in this case requested iron studies to investigate the possibility of iron overload and to screen for haemochromatosis. Iron studies are also commonly indicated in clinical practice to investigate iron deficiency, or to monitor response to treatment for these conditions (box 1).Conventional laboratory tests of iron status are often referred to as "iron studies." They include tests for serum ferritin, iron, transferrin, or total iron binding capacity (TIBC), and transferrin saturation.Iron is a key component of haemoglobin in red blood cells, myoglobin in muscle, and many metalloproteins and enzymes. It is essential for uptake of oxygen and its delivery to tissues, utilisation of oxygen by muscle cells, and mitochondrial energy production. 3 Normal iron metabolism and regulation is outlined in Figure 1⇓. The adult male body contains 3-5 g of iron. Less than 0.1% of total body iron stores circulate in plasma. Dietary Fe 3+ is reduced to Fe 2+ and transported into the enterocyte by the divalent metal transporter DMT1. Iron is exported across the basolateral membrane via the iron export protein ferroportin 1 or stored as ferritin. Transferrin bound iron binds to transferrin receptor 1 (TFR1) and is taken up into the cell via receptor mediated endocytosis. Expression of TFR1 is regulated locally by the iron demands of the cell, via binding of iron regulatory proteins. Old or damaged erythrocytes are removed from the circulation by splenic macrophages. Iron is removed from haem by haem oxygenase 1, and either stored as ferritin or released into the circulation.Regulation of iron release at a systemic level is mediated by the peptide hormone hepcidin (produced predominantly by hepatocytes) and has an inhibitory effect on iron release from cells and dietary iron absorption. Expression is controlled by complex signalling pathways. 1 What is included in iron studies?Ferritin-is the intracellular storage form of iron. A very small amount is found in serum. In inflammation, liver disease, and malignancy, ferritin levels can rise because ferritin is an acute phase protein. 4 In these patients, ferritin can appear either falsely high or normal, when in reality stores are low.Serum iron-refers to ferric ions (Fe 3+ ) bound to serum transferrin. Serum iron concentration is highly variable and is affected by dietary iron intake, inflammation, and infection. 5Transferrin-is the principal iron...

Quantitative data on red cell measures of iron status and their relation to the magnitude of the systemic inflammatory response and survival in patients with colorectal cancer

“…It is well understood that the presence of systemic inflammation of any cause leads to significant derangement of common serum measures of iron status; including total iron, transferrin saturation, and ferritin [6]. This is thought to occur due to the action of hepcidin, upregulated by the proinflammatory cytokine IL 6, resulting in inhibition of enteric iron absorption and sequestration of iron and ferritin in the liver and reticuloendothelial system [11]. Indeed, this effect has in part lead to the search for novel measures of iron status which are not affected in such a way, and in other attempts to formulate correction factors and equations to account for inflammation when using these measures of iron status [12][13].…”

“…Inflammation is recognised to lead to anaemia through three broad mechanisms, the first being the inflammation related hypoferraemia, or functional iron deficiency, driven by hepcidin described above [11]. In addition, proinflammatory cytokines tend to have a suppressive effect on erythropoiesis through their inhibitory relationship with erythroid precursors [14].…”

Normocytic anaemia is associated with systemic inflammation and poorer survival in patients with colorectal cancer treated with curative intent

“…It is clear that systemic inflammation alters both iron homeostasis and erythropoiesis through the IL-6-dependent peptide hormone hepcidin. Hepcidin acts on enterocytes and the reticuloendothelial system to reduce iron absorption from the gastrointestinal tract, and to promote sequestration of iron, therefore reducing iron available for erythropoiesis but not whole body iron stores [18]. This can lead to a state of functional iron deficiency such as that seen in patients with colorectal cancer who have a normocytic anaemia of inflammation [19].…”

<p>Effect of Integrated Pictorial Handbook Education and Counseling on Improving Anemia Status, Knowledge, Food Intake, and Iron Tablet Compliance Among Anemic Pregnant Women in Indonesia: A Quasi-Experimental Study</p>

“…The first limitation is that iron deficiency status was determined by decreased levels of serum ferritin, serum iron, and transferrin saturation with an elevated total ironbinding capacity. 62 The limitation of the present study is the fact that it did not provide these laboratory tests. The second limitation is that the birth weight outcome was measured by questionnaire-based assessments and subjective self-reports, which are subject to the abovementioned biases.…”