134 Erythrocyte and Thrombocyte Abnormalities

Hypochromic Infectious or Toxic Anemia (Secondary Anemia)

Among the various causes of lack of iron for erythropoiesis (see Fig. 44, p. 129), a special situation is represented by the internal iron shift caused by “iron pull” of the reticuloendothelial system (RES) during infections, toxic processes, autoimmune diseases, and tumors. Since this anemia results from another disorder, it is also called secondary anemia. The MCH is hypochromic, or in rare instances, normochromic, and therefore erythrocyte morphology is particularly important to diagnosis. In contrast to exogenous iron deficiency anemias, the following phenomena are often observed, depending on the severity of the underlying condition:

Anisocytosis, i.e., strong variations in the size of the erythrocytes, beyond the normal distribution. The result is that in almost every field view, some erythrocytes are either half the size or twice the size of their neighbors.

Poikilocytosis, i.e., variations in the shape of the erythrocytes. In addition to the normal round shape, numbers of oval, or pear, or tear shaped cells are seen.

Polychromophilia, the third phenomenon in this series of nonspecific indicators of disturbed erythrocyte maturation, refers to light grayblue staining of the erythrocytes, indicating severely diminished hemoglobin content of these immature cells.

Basophilic cytoplasmic stippling in erythrocytes is a sign of irregular regeneration and often occurs nonspecifically in secondary anemia.

The reticulocyte count is usually reduced in infectious or toxic anemia, unless there is concomitant hemolysis or acute blood loss.

Bone marrow analysis in secondary anemia usually shows reduced erythropoiesis and granulopoiesis with a spectrum of immature cells (“infectious/toxic bone marrow”). The information is so nonspecific that usually bone marrow aspiration is not performed. So long as all other laboratory methods are employed, bone marrow cytology is very rarely needed in cases of hypochromic anemia.

Hypochromic erythrocytes of very variable morphology indicate secondary anemia, usually in cases of infectious disease or tumor

a b

c

Fig. 46 Secondary anemia. a and b Erythrocyte morphology in secondary hypochromic anemia: the erythrocytes vary greatly in size (anisocytosis) and shape (1) (poikilocytosis), and show basophilic stippling (2). Burr cell (3), which has no specific diagnostic significance. Occasionally, the erythrocytes stain a soft gray–blue

(4) (polychromasia). c Bone marrow cell overview in secondary anemia. Cell counts in the white cell series are elevated (promyelocytes = 1), eosinophils (2), and plasma cells (3); erythropoiesis is reduced (4).

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136 Erythrocyte and Thrombocyte Abnormalities

Bone Marrow Cytology in the Diagnosis of Hypochromic

Anemias

So long as all other laboratory methods are employed, bone marrow cytology is very rarely needed in cases of hypochromic anemia.

Bone marrow cytology is rarely strictly indicated after all other available diagnostic methods have been exhausted (Table 22, p. 130). However, in doubtful cases it can usually at least help to rule out malignant disease.

In iron deficiency anemias of the most various etiologies, erythropoiesis is stimulated in a compensatory fashion, and the distribution of the markers shows the expected increase in red cell precursors. The erythropoiesis to granulopoiesis ratio increases in favor of erythropoiesis from 1:3 to 1:2, but rarely further. The red cell series shows a left shift, i.e., there are more immature red cell precursors (erythroblasts and proerythroblasts) (for normal values, see Table 4). Usually, these red cell precursors do not show any clearly atypical morphology, but the cytoplasm is basophilic even in normoblasts, according with the poor hemoglobinization. Iron staining of the bone marrow shows no sideroblasts (normoblasts containing iron granules), or only very few (!10%, norm 30–40%). A constant finding in anemia stemming from exogenous iron deficiency is absence of iron in the macrophages of the bone marrow reticulum.

Megakaryocyte counts are almost always increased in iron deficiency due to chronic hemorrhaging, but can also show increased proliferation in iron deficiency from other causes (which can lead to increased thrombocyte counts in states of iron deficiency).

In infectious or toxic (secondary) anemia, unlike exogenous iron deficiency anemia, erythropoiesis tends to be somewhat suppressed. There is no left shift and no specific anomalies are present. Granulopoiesis predominates and often shows nonspecific “stress phenomena” and a dissociation of nuclear and cytoplasmic maturation (e.g., cytoplasm that is still basophilic with promyelocytic granules in mature, banded myelocyte nuclei).

Depending on the trigger of the anemia, the monocyte, lymphocyte, or plasma cell counts are often moderately increased, and megakaryocyte counts are occasionally slightly elevated. The important indicator is iron staining of the bone marrow. The “iron pull” of the RES leads to intensive iron storage in macrophages, while the red cell precursors are almost ironfree. However, combinations do exist, when a pre-existing iron deficiency means that the iron depositories are empty even in an infectious or toxic process. Moreover, not every secondary anemia is hypochromic. Where there is concomitant alcoholism or vitamin deficiency, secondary anemia may be normochromic or hyperchromic.

Hypochromic Sideroachrestic Anemias

(Sometimes Normochromic or Hyperchromic)

In a sideroachrestic anemia existing iron cannot be utilized (achrestic = useless). This is a suspected diagnosis when serum iron levels are raised or in the high normal range, and when the erythrocytes show strong anisocytosis, poikilocytosis (with reduced average MCV), polychromophilia, and in some cases also basophilic stippling (Fig. 46). This suspicion can be further illuminated by bone marrow analysis. Unlike in infectious/toxic anemias, the red cell series is well represented. Iron staining of the bone marrow is the decisive diagnostic test, causing the iron-containing red precursor cells (sideroblasts) to stand out (hence the term “sideroblastic anemia.”) The iron precipitates often collect in a ring around the nucleus (“ringed sideroblasts”).

By far the majority of the “idiopathic sideroachrestic anemias,” as they used to be called, are myelodysplasias (see p. 106). Only a few of them appear to be hereditary or have exogenous triggers (alcoholism, lead poisoning).