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A 48-year-old man with poorly controlled type 1 diabetes is referred for evaluation of a worsening anemia. He reports a long-standing history of general fatigue and poor exercise tolerance, which he feels have worsened of late. Complications of his diabetes include severe retinopathy, peripheral vascular disease with one flight claudication, and worsening neuropathy. On physical examination, he appears chronically ill with a sallow complexion and pale conjunctiva. Findings include bilateral retinal hemorrhages, diminished pulses, and impaired sensation and position sense in both feet.

CBC: Hematocrit/hemoglobin - 29%/9.5 g/dL (IU - 95 g/L)

MCV - 91 fL MCH - 30 pg MCHC - 33 g/dL

RDW-CV - 13.5%

RDW-SD - 48 fL

WBC count - 8,800/μL

Platelet count - 150,000/μL


Normocytic and normochromic with minimal anisocytosis and no polychromasia. White cell and platelet numbers and morphology appear to be within normal limits.

Reticulocyte count/index - 2.0%/1.2

Sedimentation rate - 30 mm/h (Westergren)


  • How should this anemia be described?

  • What physiological factors may be playing a role?

  • Are there other tests that can be ordered to find the cause?

The presence and nature of an anemia may be apparent from the clinical presentation. Acute blood loss, when severe, can be expected to produce a hemorrhagic anemia; chronic blood loss will generally result in an iron deficiency anemia. More often, however, a routine measurement of the complete blood count (CBC) provides the most sensitive method for both detection and diagnosis. Thus, the clinical approach to an anemia involves both a bedside evaluation and the skilled use of the laboratory.


The signs and symptoms of an anemia are a function of its severity, its rapidity of onset, and the age of the patient. Mild anemias produce little in the way of symptoms other than a loss in stamina and an increase in heart rate and dyspnea with exercise. This reflects the ability of the hemoglobin-oxygen dissociation curve to compensate for modest reductions in the hemoglobin level in the basal state. It also shows the loss of the capacity of the hemoglobin-oxygen dissociation curve to respond to situations of increased demand once it is used to compensate for the anemia.

With more pronounced anemia, the patient's exercise capacity can be markedly reduced. Any exertion is accompanied by palpitations, dyspnea, a pounding headache, and rapid exhaustion. In younger individuals, these symptoms and signs do not appear until the hemoglobin has fallen below 7–8 g/dL (hematocrit of less than 20%–25%). However, older individuals, especially those with atherosclerotic cardiovascular disease, can become symptomatic with more modest anemia (a hemoglobin of 10–12 g/dL). This can include worsening of ischemic manifestations, including angina and claudication. Moreover, anemia can precipitate heart failure in the older patient with underlying heart disease.

The rapidity of onset of the anemia is also important. Although the hemoglobin-oxygen dissociation curve ...

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