Anemia clearly explained – from symptoms and causes to diagnostics, lab values and therapy. In this article you will learn the most important forms of anemia, understand the significance of MCV, MCH and MCHC, learn when a blood transfusion or an intravenous iron therapy is necessary, and receive a practical overview of the diagnostics of iron deficiency anemia. Ideal for preparation for the Fachsprachprüfung (FSP), knowledge exam (KP), M3 and for clinical everyday practice.

Anemia – symptoms, causes, diagnostics, laboratory and therapy

Anemia denotes a reduction in hemoglobin concentration and/or the number of erythrocytes.
It is not an independent disease, but a symptom with numerous possible causes.

Typical symptoms and clues in anemia

• Exertion-dependent fatigue and dyspnea
• Blackening of vision, presyncope or dizziness
• Concentration disturbances
• Tachycardia
• Reduced physical performance
• Pale skin and pale mucous membranes, especially conjunctivae and oral mucosa
• Cool and dry skin
• Clues to visible blood loss, e.g. hematochezia, melena or menorrhagia
• History of inadequate iron intake or malnutrition

Erythropoiesis and clinical diagnostics

Needed for the formation of red blood cells:

• Iron
• Vitamin B12
• Folic acid

The most important hormone of erythropoiesis is Erythropoietin. It is produced predominantly in the kidney.

Clinical clues

• Pale conjunctivae often indicate an Hb value below 9 g/dL.
• If the normal prominence of the palmar creases is absent when the palm is extended, this often corresponds to an Hb value of about 7–8 g/dL or below.

Physiological anemia of pregnancy

During pregnancy plasma volume increases by about 40–50%, while erythrocyte mass increases by only about 15–25%. This physiologically lowers the hemoglobin concentration.

Laboratory in anemia

Blood count

In addition to anemia, the following may occur:

• Neutropenia
• Thrombocytopenia
• Thrombocytosis

About 10% of patients with iron deficiency show such changes.

Peripheral blood smear

A blood smear provides important clues about:

• Microcytosis is found in iron deficiency anemia, thalassemia and partly in anemia of chronic disease.
• Macrocytosis occurs in vitamin B12 deficiency, folate deficiency and liver diseases.
• Schistocytes are found in thrombotic thrombocytopenic purpura (TTP), hemolytic-uremic syndrome (HUS) and disseminated intravascular coagulation (DIC).
• Spherocytes occur in hereditary spherocytosis, warm autoimmune hemolytic anemia and hemolytic transfusion reactions.
• Target cells occur in thalassemia, HbC disease and liver cirrhosis.
• Sickle cells are found in various forms of sickle cell disease, for example in HbSS, HbSC and HbS/β-thalassemia.

Iron status

To clarify an iron deficiency anemia, the following should be determined:

• Ferritin
• Serum iron
• Total iron-binding capacity (TIBC)
• Transferrin saturation

A serum ferritin below 12 ng/mL strongly indicates iron deficiency.

Important: Ferritin is an acute-phase protein and can be normal or elevated in inflammation despite iron deficiency.

Therapy of iron deficiency anemia

Treatment is guided by the cause of the anemia.

Oral iron substitution

The classical standard dose is:

Iron(II) sulfate 325 mg ≈ 65 mg elemental iron, three times daily.

According to current recommendations a lower dosage is often preferred, for example 40–100 mg elemental iron daily or every other day. This dosing is often better tolerated.

Therapy success

• Reticulocyte rise after about 7–10 days
• Increase in hemoglobin after 2–3 weeks
• Normalization usually within 1–2 months
• Continue therapy for 3–6 months to replenish iron stores
• (Stable iron deficiency anemia under iron therapy: blood count with Hb after 2–4 weeks. After Hb normalization: continue iron for about 3 more months; then check blood count and iron status.)

Transfusion indications

An erythrocyte transfusion is not based solely on the hemoglobin value but primarily on the clinical situation of the patient.

• Hb < 7 g/dL: Transfusion is recommended for most hemodynamically stable adults.
• Hb 7–8 g/dL: Transfusion with symptoms or patients at increased risk (e.g. cardiovascular disease).
• Hb 8–10 g/dL: Individual decision, e.g. in active bleeding, coronary heart disease or pronounced symptoms.
• Hb > 10 g/dL: A transfusion is usually not required.

Typical symptoms of transfusion-requiring anemia:

• Resting dyspnea
• Chest pain
• Syncope or presyncope
• Tachycardia or hemodynamic instability
• Myocardial ischemia

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When i.v. iron?

Intravenous iron substitution is preferred when oral therapy is not possible, not sufficiently effective or too slow.

• Intolerance to oral iron preparations
• Insufficient effect under oral therapy
• Malabsorption syndromes (e.g. celiac disease, inflammatory bowel diseases, post-gastric surgery state)
• Severe iron deficiency with rapid need for substitution
• Chronic renal insufficiency, especially under erythropoietin therapy
• Heart failure with iron deficiency (especially symptomatic HFrEF)
• Active chronic inflammatory bowel disease
• Preoperative in pronounced iron deficiency and planned surgery

Note: A red blood cell transfusion replaces lost oxygen carriers but does not replenish iron stores. After a transfusion – if iron deficiency is present – iron supplementation should therefore be administered in addition.

Note

• The most common cause of iron deficiency anemia in adults is chronic blood loss.
• In men and postmenopausal women, a gastrointestinal source of bleeding should always be sought.
• Ferritin is the most important laboratory parameter for detecting iron deficiency.
• MCV, MCH and MCHC help classify the anemia.
• Reticulocytes indicate the activity of the bone marrow.
• The cause of the anemia should always be treated – not just the low hemoglobin value.