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636 Part VI: The Erythrocyte Chapter 43: Iron Deficiency and Overload 637

Anemia of Chronic Renal Disease Sideroblastic Anemia
Iron deficiency is frequent in patients with chronic renal disease (Chap. In this heterogeneous group of disorders (Chap. 59), the blood findings
37). Iron-deficiency anemia is particularly difficult to diagnose in often simulate those of iron-deficiency anemia. Reticulocytosis is usu-
patients with chronic renal disease (Chap. 37) where iron delivery to the ally absent, and the serum iron concentration and serum ferritin is gen-
marrow is inadequate because of coexisting inflammation and because erally normal or increased. Marrow examination shows characteristic
of increased demands from pulsatile erythropoiesis as a result of ery- ring sideroblasts and increased amounts of stainable iron.
thropoiesis-stimulating agents. Because the problem is fairly common,
and perhaps because of interest in identifying those patients who can Congenital Dyserythropoietic Anemia
benefit from iron therapy and decreasing their use of erythropoiesis- In the rare congenital dyserythropoietic anemias (Chap. 39), erythro-
stimulating agents, a large number of studies have been done to deter- cyte morphologic abnormalities may resemble those of iron deficiency
mine the best way to diagnose iron deficiency in patients undergoing or thalassemia (Chap. 48). In general, in congenital dyserythropoietic
extracorporeal dialysis. The diagnostic problem is further complicated anemias, poikilocytosis is very striking and occurs with less reduction
by the common occurrence of “functional iron deficiency,” that is, a in MCV than in iron deficiency or thalassemias. Often, however, such
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state in which iron stores are adequate but iron delivery to the marrow is cases are believed to be thalassemic until the marrow is examined.
insufficient to meet the increased kinetic requirements of erythropoie-
sis stimulated by intermittent use of erythropoietin and related agents. Megaloblastic Anemia
If response to intravenous iron therapy is used to diagnose iron defi- In pernicious anemia and other types of megaloblastic anemia (Chap. 41),
ciency, even many patients with abnormally high ferritins will be iron the blood film usually shows changes sufficiently distinctive that there is
deficient. 150,189 High serum ferritins do not preclude a response to IV little difficulty in differential diagnosis. One potential source of error is
iron, not even in patients with chronic kidney disease who are not on the change in serum iron concentration that occurs after therapy. In the
hemodialysis. Although measurements of reticulocyte hemoglobin patient with pernicious anemia or folic acid deficiency, early after start-
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and percent of hypochromic erythrocytes show promise as markers of ing treatment, the serum iron concentration decreases markedly as iron
response to iron therapy, there is insufficient evidence that any individ- is used rapidly for hemoglobin synthesis. Thus the finding of a low
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ual biomarker or combination of biomarkers can reliably predict the serum iron concentration in such circumstances should not be taken
response to iron treatment in chronic kidney disease. 191
as evidence of iron deficiency. Iron-deficiency anemia and anemia as a
consequence of folic acid or vitamin B deficiency may coexist. During
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Anemia of Hemolytic Disease the course of treatment, with the rapid increase in the number of red
Hemolytic disease can usually be distinguished from iron-deficiency cells, the typical manifestations of severe iron deficiency may develop.
anemia on the basis of the blood film. The marked polychromatophilia, The mixture of microcytic-hypochromic and normocytic-normochro-
spherocytosis, schistocytes, Heinz bodies, basophilic stippling, and mic cells has been called dimorphic anemia (see “Coexisting Microcytic
other morphologic features characteristic of various types of hemolysis Anemia” in Chap. 41).
usually are not seen in iron-deficiency anemia. Furthermore, reticulo-
cytosis is usually marked in hemolytic disorders but minimal or absent
in iron-deficiency anemia. However, there are some outstanding excep- Anemia of Hypothyroidism
tions to these generally valid principles. The anemia of severe hypothyroidism (myxedema; Chap. 38) is usually
In unstable hemoglobin disorders, such as hemoglobin H disease normochromic and normocytic and may be accompanied by mild-to-
or hemoglobin Köln disease, erythrocytic hypochromia may be pro- moderate depression of serum iron concentration. Marrow examina-
nounced. In these disorders, there is moderate reticulocytosis, which tion may be required to determine whether iron deficiency is present,
helps to differentiate them from iron-deficiency anemia. The serum iron especially as iron deficiency often complicates myxedema because of
concentration is normal or increased. Chapter 49 discusses the detec- menorrhagia, which is common in this disorder.
tion of unstable hemoglobins.
When there is chronic intravascular hemolysis, erythrocytes in the Therapeutic Trial
blood film may display marked morphologic abnormalities, such as burr In the final analysis, the response to iron therapy is the proof of correct-
cells and schizocytes. Yet because of loss of iron in the urine, iron defi- ness of diagnosis of iron-deficiency anemia. Furthermore, some phy-
ciency may be the dominant cause of the resulting anemia. Evaluation of sicians or patients may not have access to all the techniques described
iron content in marrow aspirates or measurement of serum iron concen- for diagnosis of iron-deficiency anemia. In this event, the patient’s
tration and TIBC may clarify the diagnosis in this form of anemia. response to therapy may become a primary diagnostic measure. Iron
administration in such a therapeutic trial is usually by the oral route,
Hypoplastic and Aplastic Anemia but intravenous iron can be used if there is evidence or strong suspicion
In their early phases, these disorders cannot reliably be differentiated of coexisting inflammation, iron malabsorption, or intolerance of oral
from mild iron-deficiency anemia on the basis of erythrocyte morphol- iron preparations. A therapeutic trial under any circumstances should
ogy alone (Chap. 35). The reticulocyte count is generally less than 0.5 be followed carefully. If the cause of anemia is iron deficiency, adequate
percent in hypoplastic or aplastic anemia. The presence of neutrope- iron therapy should result in reticulocytosis with a peak occurring after
nia and thrombocytopenia suggests a diagnosis of aplastic anemia, but 1 to 2 weeks of therapy, although if anemia is mild, the reticulocyte
mild neutropenia may also occur in iron-deficiency anemia. The serum response may be minimal. A significant increase in the hemoglobin
iron concentration is usually increased in aplastic anemia; and the per- concentration of the blood should be evident 3 to 4 weeks later, and
centage transferrin saturation is then elevated. Marrow aspiration may the hemoglobin concentration should attain a normal value within 2
produce scant material for cytologic study, and marrow biopsy may be to 4 months. Unless there is evidence of continued substantial blood
necessary. An iron stain usually reveals increased amounts of hemosid- loss, the absence of response to oral or, when appropriate, parenteral
erin in aplastic or hypoplastic anemia. However, if chronic bleeding has iron must be taken as evidence that iron deficiency is not the cause of
occurred, for example, as a consequence of thrombocytopenia, iron anemia. Iron therapy should be discontinued and another cause for the
stores may be depleted. anemia sought.

Kaushansky_chapter 43_p0627-0650.indd 637 9/17/15 6:27 PM