Page 579 - Hematology_ Basic Principles and Practice ( PDFDrive )

494 Part V Red Blood Cells

A B C D E
Fig. 37.2 ANEMIA OF CHRONIC DISEASE. (A) Peripheral blood typically exhibits a normochromic,
normocytic anemia. (B, C) Bone marrow examination is sometimes performed to rule out other causes of
anemia. Typically, the bone marrow is morphologically normal. (D, E) Prussian blue iron stain shows increased
iron stores with increased histiocytic iron but decreased sideroblastic iron.

Other researchers have shown that, in acute inflammation, serum
ferritin levels greater than 3500 ng/mL can coexist with absent bone Treatment of Anemia of Chronic Diseases
marrow iron stores tested by aspirate. In ACD, ferritin levels can
be normal or elevated, reflecting increased iron retention in the Treating ACD is unnecessary if the patient is asymptomatic. However,
if the anemia is symptomatic or severe, treatment of the anemia itself
reticuloendothelial system (RES). Although normograms corrected may be indicated. Epidemiologic studies, such as those in patients
for the degree of inflammation present have been published, most with heart failure, HIV, cancer, or kidney disease, suggest physiologic
investigators maintain that serum iron studies cannot predictably rule and subjective improvement in signs and symptoms after treatment
out iron deficiency. Additional functional tests of iron status have for anemia. However, treatments need to be individualized because
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been developed, including soluble transferrin receptors (sTFRs), the risks of erythropoiesis-stimulating agents or iron therapy in noniron
hemoglobin concentration in reticulocytes (CHr), percent of deficient subjects are theoretically real and practically unknowable
hypochromic RBCs (%HYPO), and serum hepcidin levels, in an given the variety of underlying conditions that are incorporated under
attempt to differentiate ACD alone from ACD complicated with the rubric of chronic disease.
The first priority in ACD should be to correct any reversible contribu-
iron deficiency. sTFR levels are elevated in iron deficiency anemia. tors to the anemia. Because the extent of ACD mirrors the activity of the
Several studies show that the numbers of sTFRs on erythroblasts are underlying disease, all efforts should be made to treat the underlying
lower, occasionally dramatically so, in RA patients with ACD than in disease. Furthermore, efforts to correct anemia should be modulated
patients with iron deficiency anemia. The sTFR to the log of serum by the recognition that the “optimal” target hemoglobin for subjects
ferritin ratio may be useful in identifying iron deficiency in the pres- with ACD is not known. Observations from profoundly anemic subjects
ence of ACD, but is not widely available. While a low ratio index (<1) without inflammation but religiously opposed to transfusions have sug-
suggests ACD, an index >2 is indicative of a combination of ACD gested a physiologic cutoff for hemoglobin of 5 g/dL, below which
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with iron deficiency. An algorithm that incorporates hepcidin levels increased mortality is seen. In addition, acutely ill patients have not
has been developed to increase specificity for iron deficiency in ACD, been shown to benefit, in randomized, controlled studies, from transfu-
but still requires prospective validation. Hemoglobin concentration sion “triggers” above 7 g/dL. Nonetheless, symptomatic improvement
is seen in subjects with a range of chronic diseases who are treated
in reticulocytes (CHr), distinct from indices of mature RBCs, can for anemia of a more modest degree.
reflect the recent status of iron stores in normal or EPO-induced Transfusion therapy may be the most common form of treatment of
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erythropoiesis. sTFR-, CHr-, and hepcidin-based algorithms for symptomatic ACD. Newer targeted therapies are emerging in ACD, but
iron-replete and iron-deficient ACD are being developed, and a are not yet standard-of-care.
combination of these is likely to be useful in diagnosing and dif-
ferentiating ACD from ACD with iron deficiency. However, none are
fully characterized or yet widely incorporated into clinical practice,
and the diagnosis of ACD remains a clinical one.
In a study of mostly older patients with an idiopathic anemia (10 TREATMENT
± 0.6 g/dL), a bone marrow aspirate with biopsy was found to add
little to physical examination and serology. However, a bone marrow The anemia associated with chronic illness is often mild. In RA, the
examination may be necessary to rule out other diagnoses, includ- annual incidence of anemia (<10 g/dL), proportionate with markers
ing iron deficiency, malignancy (e.g., myelodysplastic syndrome), of inflammation, was only 1.5%, with a lifetime prevalence of 13.7%.
or infection (see Fig. 37.1). Although the clinical setting in which Similarly, in cancer subjects referred for radiation therapy, only 16%
anemia is found helps with the diagnosis of ACD, in 30% of cases had hemoglobin levels of less than 10 g/dL. Although over time the
no chronic illness can be identified. anemia can become more severe, the correction of ACD per se may
ACD may also be undiagnosed in complicated medical patients. be unnecessary, especially if the primary disorder contributing to the
Although anemia of renal failure is associated with absolute EPO anemia can be treated and reversed.
deficiency, it is also considered an inflammatory condition with There may also be teleologic benefits in the pathophysiologic
associated elevations in cytokine levels. In addition, patients on processes that contribute to ACD. Although fever associated with
hemodialysis may have occult infections (e.g., of nonfunctioning infections inhibits bacterial growth, decreased iron concentrations
arteriovenous grafts) with associated markers of inflammation and (as seen in ACD) synergize with pyrexia to inhibit bacterial growth.
EPO resistance; removal of these grafts may correct the anemia. This “nutritional immunity” is postulated to be an adaptive factor
Patients with congestive heart failure and anemia have elevated that contributes to ACD. Further, elevations in serum iron have been
TNF levels, proportional to the severity of anemia, with EPO levels associated with an increase in cancer risk. However, iron sequestration
inadequate to the degree of anemia, all of which are consistent is not devoid of risks and ACD can occasionally be severe and warrant
with ACD. immediate attention.