128 Erythrocyte and Thrombocyte Abnormalities

Clinically Relevant Classification Principle for Anemias: Mean Erythrocyte Hemoglobin Content (MCH)

In current diagnostic practice, erythrocyte count and hemoglobin content (grams per 100 ml) in whole blood are determined synchronously. This allows calculation of the hemoglobin content per individual erythrocyte (mean corpuscular hemoglobin, MCH) using the following simple formula (p. 10):

Hb (g/dl) · 10

Ery (106/µl)

The mean cell volume, hematocrit, MCH, and erythrocyte size can be used for various calculations (Table 22; methods p. 10, normal values Table 2, p. 12). Despite this multiplicity of possible measures, however, in routine diagnostic practice the differential diagnosis in cases of low Hb concentration or low erythrocyte counts relies above all on the MCH, and most forms of anemia can safely be classified by reference to the normal data range of 26–32 pg Hb/cell (1.61–1.99 fmol/cell) as normochromic (within the normal range), hypochromic (below the), or hyperchromic (above the norm). The reticulocyte count (p. 11) provides important additional pathophysiological information. Anemias with increased erythrocyte production (hyper-regenerative anemias) suggest a high reticulocyte count, while anemias with diminished erythrocyte production (hyporegenerative anemias) have low reticulocyte counts (Table 22).

It should be noted that hyporegenerative anemias due to iron or vitamin deficiency can rapidly display hyper-regeneration activity after only a short course of treatment with iron or vitamin supplements (up to the desirable “reticulocyte crisis”).

The practical classification of anemia starts with the MCH:

—26–32 pg = normochromic

—Less than 26 pg = hypochromic

—More than 32 pg = hyperchromic

Hypochromic Anemias

Iron Deficiency Anemia

Most anemias are hypochromic. Their usual cause is iron deficiency from various causes (Fig. 44). To distinguish quickly between real iron deficiency and an iron distribution disorder, iron and ferritin levels should be determined.

130 Erythrocyte and Thrombocyte Abnormalities

Table 22 Diagnostic findings and work-up for the most important disorders of the red cell series

Diagnostic steps proceed from left to right. The next step is usually unnecessary; :. the next step is optional; #the next step is obligatory. n = normal value, != lower than normal, "= elevated, ( ) = test not relevant, BSG = erythrocyte sedimentation rate.

""

PTT n

132 Erythrocyte and Thrombocyte Abnormalities

Table 23 Normal ranges for physiological iron and its transport proteins

TIBC = Total iron binding capacity.

This usually renders determination of transferrin and total iron binding capacity (TIBC) unnecessary. If samples are being sent away to a laboratory, it is preferable to send serum produced by low-speed centrifugation, since the erythrocytes in whole blood can become mechanically damaged during shipment and may then release iron. Table 23 shows the variation of serum iron values according to gender and age.

It is important to note that acute blood loss causes normochromic anemia. Only chronic bleeding or earlier serious acute blood loss leads to iron deficiency manifested as hypochromic anemia.

Iron Deficiency and Blood Cell Analysis Focusing on the erythrocyte morphology is the quickest and most efficient way to investigate hypochromic anemia when the serum iron has dropped below normal values. In hypochromic anemia with iron and hemoglobin deficiency (whether due to insufficient iron intake or an increased physiological iron requirement), erythrocyte size and shape does not usually vary much (see Fig. 45). Only in advanced anemias (from approx. 11 g/dl, equivalent to 6.27 mmol/l Hb) are relatively small erythrocytes (microcytes) with reduced MCV and MCH and grayish stained basophilic erythrocytes (polychromatic erythrocytes) seen, indicating inadequate hemoglobin content. Cells with the appearance of relatively large polychromatic erythrocytes are reticulocytes. The details of their morphology can be seen after supravital staining (p. 141). A few target cells (p. 139) will be seen in conditions of severe iron deficiency.

In severe hemoglobin deficiency (! 8 g/dl, equivalent to 4.96 mmol/l) the residual hemoglobin is found mostly at the peripheral edge of the erythrocyte, giving the appearance of a ring-shaped erythrocyte.

Small, hemoglobin-poor erythrocytes indicate iron deficiency

a b

c d

Fig. 45 Iron deficiency anemia. a and b Erythrocyte morphology in iron deficiency anemia: ring-shaped erythrocytes (1), microcytes (2) faintly visible target cells (3), and a lymphocyte (4) for size comparison. Normal-sized erythrocytes (5) after transfusion. c Bone marrow cytology in iron deficiency anemia shows only increased hematopoiesis and left shift to basophilic erythroblasts (1). d Absence of iron deposits after iron staining (Prussian blue reaction). Megakaryocyte (1).

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