Main causes of development (Etiology)
Etiological factors of IDA are conveniently divided into three broad groups: impaired intake, chronic blood loss, and increased iron expenditure.
- Chronic blood loss. This is the most common cause of iron store depletion. The source may be:
- Gastrointestinal tract: peptic ulcer disease of the stomach and duodenum, hemorrhoids, esophageal varices, polyposis, ulcerative colitis, and oncological processes.
- Gynecology: dysfunctional uterine bleeding (metrorrhagia, e.g., associated with uterine fibroids).
- Respiratory system: diseases involving destruction of lung tissue (specifically, lung cancer).
- Inadequate intake or absorption.
- Dietary deficiency (low iron content in the diet).
- Malabsorption syndromes and celiac disease.
- Chronic gastrointestinal diseases and post-gastrectomy states that impair trace element absorption.
- Increased demand. Iron expenditure increases during physiological states (pregnancy, lactation, periods of active growth and puberty) and pathological processes (chronic infections, oncology). Store depletion may also be iatrogenic, for example, during erythropoietin therapy, which sharply stimulates erythropoiesis.
Pathogenesis and sideropenic syndrome
The clinical presentation consists of manifestations of the underlying disease (the source of bleeding) and sideropenia itself. If anemia develops slowly, the body manages to employ compensatory mechanisms: tissue oxygen extraction increases and hemodynamics change. As a result, patients may remain asymptomatic for a long time even with a significant drop in hemoglobin, although their exercise tolerance decreases.
Tissue iron deficiency leads to reduced activity of iron-containing enzymes and the development of sideropenic syndrome. Its main manifestation is trophic disorders and mucosal atrophy throughout the entire GI tract. Atrophy of the pharyngeal and laryngeal mucosa causes dysphagia, which is considered a precancerous condition.
Clinical presentation: complaints and physical examination
Subjective symptoms are caused by both hypoxia and enzyme deficiency. Patients report increased fatigue, irritability, headaches, and neurological disorders in the form of paresthesias. A specific marker is the historical term chlorosis — pica chlorotica. This involves perversion of taste (an irresistible craving to eat chalk, clay, coal, glue) and smell (an addiction to sharp smells of gasoline or chemicals). A burning sensation of the tongue is also characteristic.
On physical examination, signs of hypoxia and trophic disorders are detected:
- Pallor of the skin and mucous membranes.
- Oral cavity lesions: stomatitis and atrophic glossitis (smoothing of the lingual papillae).
- Changes in skin appendages: brittle nails and hair, and koilonychia (spoon-shaped nail depressions), which is rarely seen nowadays.
- Cardiovascular changes: tachycardia and systolic murmurs characteristic of anemic syndrome.
Laboratory diagnostics
The diagnosis is confirmed by a comprehensive analysis of peripheral blood and biochemical markers of iron metabolism.
Hemogram:
- Decreased erythrocyte count and hemoglobin level.
- Morphological changes: hypochromia and microcytosis. In mild deficiency, anemia may be normochromic, and the earliest signs are anisocytosis (varying size) and poikilocytosis (variation in erythrocyte shape).
- Reticulocytes remain normal or decreased (hyporegenerative character of the anemia).
- Leukocytes may be decreased (leukopenia), while platelets show either thrombocytopenia or thrombocytosis.
Blood biochemistry:
- Serum iron drops below 10 µmol/L (e.g., in severe blood loss, it can drop to 6 µmol/L).
- Plasma ferritin content decreases (marker of complete store depletion).
- The level of free transferrin and total iron-binding capacity (TIBC) increases, while the transferrin iron saturation percentage drops sharply.
Myelogram (sternal puncture): Reveals reactive bone marrow "irritation" — erythroid hyperplasia. However, the degree of red blood cell proliferation does not correspond to the severity of anemia, indicating ineffective erythropoiesis.
Pre-analytical rules: Intake of iron supplements causes a false increase in serum iron, so they must be discontinued at least 24 hours before blood sampling. Differential diagnosis with anemia of chronic disease is also required, in which iron levels drop against the background of inflammation or tumor.
Principles of treatment and evaluation of efficacy
After establishing the diagnosis of IDA, an obligatory step is finding and eliminating the source of bleeding (e.g., hysterectomy for fibroids complicated by metrorrhagia).
Pharmacotherapy: Iron salt preparations (lactate, sulfate, carbonate, gluconate) are used. The route of administration is predominantly oral. Strict indications for parenteral administration are limited to impaired intestinal absorption or exacerbated peptic ulcer disease. Treatment is supplemented with diet therapy focusing on meat products as a source of heme iron.
Therapy ex juvantibus and efficacy criteria: In doubtful cases, trial treatment with iron preparations is prescribed. The adequacy of therapy is evaluated by clear time criteria:
- Day 7–10: a reticulocyte crisis develops (peak increase in reticulocyte count).
- Week 3–4: a significant increase in hemoglobin level is observed.
- Month 2: complete normalization of hemoglobin level.
Briefly: answers to topical questions
What diseases must be differentiated from iron-deficiency anemia?
Iron-deficiency anemia must be differentiated from other microcytic and hypochromic anemias presenting with a similar hematological picture.
These diseases include:
- Anemia of chronic disease — complicates chronic inflammatory and oncological processes.
- Thalassemias (α- and β-thalassemias) — hypochromic anemias with iron overload.
- Sideroblastic anemias — conditions with sufficient iron stores but impaired incorporation into the heme structure (lead poisoning, pyridoxine-responsive anemia).
- Porphyrias.
- Other types of deficiency anemias.
Which specific iron-containing enzymes decrease in activity during tissue iron deficiency?
During tissue iron deficiency, the structure and activity of iron-containing enzymes and compounds are impaired.
The sources explicitly name:
- Catalase.
- Glutathione peroxidase.
- Peroxidases.
- Cytochromes.
Additionally, iron deficiency impairs the synthesis of iron-containing compounds, including myoglobin. This leads to decreased activity of antioxidant factors, increased lipid peroxidation, and tissue damage.
Groups of IDA causes: Lost (bleeding), Didn't get (diet/malabsorption), Spent (pregnancy/growth).
Class and exam questions
Why might complaints be absent in the early stages of chronic blood loss?
With the slow development of anemia, powerful compensatory mechanisms are activated: tissue oxygen extraction increases, and adaptive hemodynamic changes occur.
How does erythrocyte morphology change over time during the development of IDA?
In mild deficiency, anisocytosis and poikilocytosis appear first, and anemia may remain normochromic. Microcytosis and hypochromia develop at later stages of store depletion.
What is the main rule for preparing a patient for a serum iron blood test?
It is necessary to discontinue iron supplements at least 24 hours before blood collection, otherwise the results will be falsely elevated.
When is a reticulocyte crisis expected during iron supplementation therapy?
The peak increase in reticulocytes (reticulocytic crisis) with adequate therapy occurs on days 7–10 of supplementation.
What else to study on this topic
- Differential diagnosis of IDA and anemia of chronic disease (ACD)
- Pathophysiology of atrophic changes in the GI mucosa in tissue iron deficiency
- Mechanisms of iron absorption and the role of gastric resection in the development of sideropenia
- Clinical features of posthemorrhagic IDA in gynecology (case analysis)
- Effect of erythropoietin therapy on systemic iron metabolism
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