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  1. Hereditary

    1. Enzyme defects, such as pyruvate kinase or glucose-6-phosphate dehydrogenase (G6PD) deficiency

    2. Hemoglobinopathies, such as sickle cell anemia

    3. RBC membrane abnormalities, such as spherocytosis

  2. Acquired

    1. Hypersplenism

    2. Immune

      1. Autoimmune: warm IgG, cold IgM, cold IgG

      2. Drug induced: autoimmune or hapten

    3. Mechanical

      1. Macroangiopathic (marching, prosthetic valves)

      2. Microangiopathic: disseminated intravascular coagulation (DIC), thrombotic thrombocytopenic purpura (TTP), and hemolytic uremic syndrome (HUS)

    4. Infections, such as malaria

    5. Toxins, such as snake venom and aniline dyes

    6. Paroxysmal nocturnal hemoglobinuria

Figure 6-1 outlines the approach to evaluating anemia, assuming acute bleeding has been excluded.

  1. Symptoms in chronic anemia are due to decreased oxygen delivery to the tissues.

    1. Fatigue is a common but not very specific symptom.

    2. Dyspnea on exertion often occurs.

    3. Exertional chest pain occurs most often in patients with underlying coronary artery disease or severe anemia or both.

    4. Palpitations or tachycardia can occur.

    5. Edema is sometimes seen.

      1. It is due to decreased renal blood flow leading to neurohormonal activation and salt and water retention, similar to that seen in heart failure.

      2. However, in contrast to the low cardiac output seen in patients with heart failure, the cardiac output in patients with anemia is high.

    6. Mild anemia is often asymptomatic.

  2. Symptoms of hypovolemia occur only in acute anemia caused by large volume blood loss.

  3. Conjunctival rim pallor

    1. Present when the anterior rim of the inferior palpebral conjunctiva is the same pale pink color as the deeper posterior aspect, rather than the normal bright red color of the anterior rim.

    2. image The presence of conjunctival rim pallor strongly suggests the patient is anemic (LR+ 16.7).

    3. However, the absence of pallor does not rule out anemia.

  4. Palmar crease pallor has an LR+ of 7.9.

  5. Pallor elsewhere (facial, nail bed) is not as useful, with LR+ < 5.

  6. No physical sign rules out anemia.

  7. The overall sensitivity and specificity of the physical exam for anemia is about 70%.

    image Order a CBC if patients have symptoms that suggest anemia, even without physical exam signs, or if you observe conjunctival rim or palmar crease pallor.

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