Iron Deficiency Anemia Clinical Presentation

Updated: Aug 23, 2023
  • Author: James L Harper, MD; Chief Editor: Emmanuel C Besa, MD  more...
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Although iron deficiency anemia is a laboratory diagnosis, a carefully obtained history can facilitate its recognition. The history can also be useful in establishing the etiology of the anemia and, perhaps, in estimating its duration. Iron deficiency anemia often develops gradually, with small amounts of blood loss. Such persons may remain asymptomatic until their iron stores become sufficiently depleted to compromise red cell production and other tissues, at which point fatigue and other symptoms arise. 

One half of patients with moderate iron deficiency anemia develop pagophagia. Usually, they crave ice to suck or chew. [14] Occasionally, patients are seen who prefer cold celery or other cold vegetables in lieu of ice. Leg cramps, which occur on climbing stairs, also are common in patients deficient in iron. An association with chronic daily headache has been reported, with the severity of headache correlating with the severity of the iron deficiency anemia. [15]

Often, patients can identify a distinct point in time when these symptoms first occurred, providing an estimate of the duration of the iron deficiency.

Fatigue and diminished capability to perform hard labor are attributed to the lack of circulating hemoglobin; however, they occur out of proportion to the degree of anemia and probably are due to a depletion of proteins that require iron as a part of their structure.

Increasing evidence suggests that deficiency or dysfunction of nonhemoglobin proteins has deleterious effects. These include muscle dysfunction, pagophagia, dysphagia with esophageal webbing, poor scholastic performance, altered resistance to infection, and altered behavior.

Dietary history

A dietary history is important. Vegetarians are more likely to develop iron deficiency, unless their diet is supplemented with iron. National programs of dietary iron supplementation are initiated in many portions of the world where meat is sparse in the diet and iron deficiency anemia is prevalent. Unfortunately, affluent nations also supplement iron in foodstuffs and vitamins without recognizing the potential contribution of iron to free radical formation and the prevalence of genetic iron overloading disorders.

Elderly patients who are in poor economic circumstances and do not wish to seek aid may try to survive on a “tea and toast” diet. They may also be hesitant to share this dietary information. This group is far more likely to develop protein-calorie malnutrition before they develop iron deficiency anemia.

A fundamental concept is that after age 1 year, dietary deficiency alone is not sufficient to cause clinically significant iron deficiency, so a source of blood loss should always be sought as part of the management of a patient with iron deficiency anemia. Infants and toddlers are the primary risk groups for dietary iron deficiency anemia. Neonates who double their birthweight are a special risk group. Also see Pediatric Acute Anemia and Pediatric Chronic Anemia.

Pica is not a cause of iron deficiency anemia; pica is a symptom of iron deficiency anemia. It is the link between iron deficiency anemia and lead poisoning, which is why iron deficiency anemia should always be sought when a child is diagnosed with lead poisoning. Hippocrates recognized clay eating; however, modern physicians often do not recognize it unless the patient and family are specifically queried. Both substances decrease the absorption of dietary iron. Clay eating occurs worldwide in all races, though it is more common in Asia Minor. Starch eating is a habit in females of African heritage, and it often starts in pregnancy as a treatment for morning sickness.

History of hemorrhage

Two thirds of body iron is present in circulating red blood cells as hemoglobin. Each gram of hemoglobin contains 3.47 mg of iron; thus, each mL of blood lost from the body (hemoglobin 15 g/dL) results in a loss of 0.5 mg of iron.

Bleeding is the most common cause of iron deficiency, either from parasitic infection (hookworm) or other causes of blood loss. With bleeding from most orifices (hematuria, hematemesis, hemoptysis), patients will present before they develop chronic iron deficiency anemia; however, gastrointestinal bleeding may go unrecognized. Patients often do not understand the significance of a melanotic stool.

Excessive menstrual losses may be overlooked. Unless menstrual flow changes, patients typically do not seek medical attention for menorrhagia. If the clinician asks, these patients generally report that their menses are normal. Because of the marked differences among women with regard to menstrual blood loss (10-250 mL per menses), query the patient about a specific history of clots, cramps, and the use of multiple tampons and pads. For more information, also see Menorrhagia.


Physical Examination

Anemia produces nonspecific pallor of the mucous membranes. A number of abnormalities of epithelial tissues are described in association with iron deficiency anemia. These include esophageal webbing, koilonychia, glossitis, angular stomatitis, and gastric atrophy.

The exact relationship of these epithelial abnormalities to iron deficiency is unclear and may involve other factors. For example, in publications from the United Kingdom, esophageal webbing and atrophic changes of the tongue and the corner of the mouth are reported in as many as 15% of patients with iron deficiency; however, they are much less common in the United States and other portions of the world.

Splenomegaly may occur with severe, persistent, untreated iron deficiency anemia. This is uncommon in the United States and Europe.



Iron deficiency anemia diminishes work performance by forcing muscles to depend on anaerobic metabolism to a greater extent than they do in healthy individuals. This change is believed to be attributable to deficiency in iron-containing respiratory enzymes rather than to anemia.

Severe anemia due to any cause may produce hypoxemia and enhance the occurrence of coronary insufficiency and myocardial ischemia. Likewise, it can worsen the pulmonary status of patients with chronic pulmonary disease.

Defects in structure and function of epithelial tissues may be observed in iron deficiency. Fingernails may become brittle or longitudinally ridged, with the development of koilonychia (spoon-shaped nails). The tongue may show atrophy of the lingual papillae and develop a glossy appearance. Angular stomatitis may occur with fissures at the corners of the mouth.

Dysphagia may occur with solid foods, with webbing of the mucosa at the junction of the hypopharynx and the esophagus (Plummer-Vinson syndrome); this has been associated with squamous cell carcinoma of the cricoid area. Atrophic gastritis occurs in iron deficiency with progressive loss of acid secretion, pepsin, and intrinsic factor and development of an antibody to gastric parietal cells. Small intestinal villi become blunted.

Cold intolerance develops in one fifth of patients with chronic iron deficiency anemia and is manifested by vasomotor disturbances, neurologic pain, or numbness and tingling.

Rarely, severe iron deficiency anemia is associated with papilledema, increased intracranial pressure, and the clinical picture of pseudotumor cerebri. These manifestations are corrected with iron therapy.

Impaired immune function is reported in subjects who are iron deficient, and there are reports that these patients are prone to infection; however, because of the presence of other factors, the current evidence is insufficient to establish that this impairment is directly due to iron deficiency.

Children deficient in iron may exhibit behavioral disturbances. Neurologic development is impaired in infants and scholastic performance is reduced in children of school age. The intelligence quotients (IQs) of schoolchildren deficient in iron are reported to be significantly lower than those of their nonanemic peers. Behavioral disturbances may manifest as an attention deficit disorder. Growth is impaired in infants with iron deficiency. The neurologic damage to an iron-deficient fetus results in permanent neurologic injury and typically does not resolve on its own. Iron repletion stabilizes the patient so that his or her status does not further decline.

A case-control study of 2957 children and adolescents with iron deficiency anemia and 11,828 healthy controls from the Taiwan National Health Insurance Database found that iron deficiency anemia is associated with an increased risk for psychiatric disorders. After adjusting for demographic data and risk factors for iron deficiency anemia, children and adolescents with iron deficiency anemia were at higher risk for the following [16] :

  • Unipolar depressive disorder
  • Bipolar disorder
  • Anxiety disorder
  • Autism spectrum disorder
  • Attention-deficit/hyperactivity disorder
  • Tic disorder
  • Delayed development
  • Mental retardation