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Especially: thalassemia Hb electro- phoresis and further tests " n "/(n) n/" (!/n) Aplastic ane- mia or bone marrow carci- nosia Search for trig- ger or tumor Hypoplasia of all cell series, or car- cinoma cells p. 146, 148, 150 n n n/" Vitamin B12 folic acid ! (!) Megaloblastic anemia Gastroscopy, determination of antibodies, possibly Schilling test ........................ Erythropoietic megaloblasts p. 152 n/! n ! " " Polyeythemia, DD: hypergam- maglobuline- mia ALP, progress- ion Erythropoiesis" p. 162 n n ! duration of hemor- rhaging "" PTT n – Thrombocyto- penic purpura (ITP) Search for trig- gers, possibly also for anti- bodies Elevated mega- karyocyte count p. 166 Hypochromic Anemias 132 Table 23 Normal ranges for physiological iron and its transport proteins Old units SI units Serum iron Newborns 150–200µg/dl 27–36µmol/l Adults Female 60–140µg/dl 11–25µmol/l Male 80–150µg/dl 14–27µmol/l TIBC 300–350µg/dl 54–63µmol/l Transferrin 250–450µg/dl 2.5–4.5 g/l Serum ferritin 30–300µg/l (15–160µg/l premenopausal) TIBC = Total iron binding capacity. Erythrocyte and Thrombocyte Abnormalities This usually renders determination of transferrin and total iron binding capacity (TIBC) unnecessary. If samples are being sent away to a labora- tory, it is preferable to send serum produced by low-speed centrifugation, since the erythrocytes in whole blood can becomemechanically 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 ane- mia. 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 mor- phology is the quickest andmost efficientway to investigate hypochromic anemia when the serum iron has dropped below normal values. In hypo- chromic anemia with iron and hemoglobin deficiency (whether due to in- sufficient iron intake or an increased physiological iron requirement), erythrocyte size and shape does not usually varymuch (see Fig.45). Only in advanced anemias (from approx. 11 g/dl, equivalent to 6.27mmol/l Hb) are relatively small erythrocytes (microcytes) with reduced MCV and MCH and grayish stained basophilic erythrocytes (polychromatic eryth- rocytes) seen, indicating inadequate hemoglobin content. Cells with the appearance of relatively large polychromatic erythrocytes are reticulo- cytes. The details of theirmorphology 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 (! 8g/dl, equivalent to 4.96mmol/l) the residual hemoglobin is found mostly at the peripheral edge of the erythrocyte, giving the appearance of a ring-shaped erythrocyte. 133 a c b d Small, hemoglobin-poor erythrocytes indicate iron deficiency Fig. 45 Iron deficiency anemia. a and b Erythrocyte morphology in iron deficien- cy 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 in- creased hematopoiesis and left shift to basophilic erythroblasts (1). d Absence of iron deposits after iron staining (Prussian blue reaction). Megakaryocyte (1). 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 re- sults from another disorder, it is also called secondary anemia. TheMCH is hypochromic, or in rare instances, normochromic, and therefore erythro- cytemorphology is particularly important to diagnosis. In contrast to exo- genous iron deficiency anemias, the following phenomena are often ob- served, depending on the severity of the underlying condition: " Anisocytosis, i.e., strong variations in the size of the erythrocytes, be- yond 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 addi- tion 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 gray- blue staining of the erythrocytes, indicating severely diminished hemoglobin content of these immature cells. " Basophilic cytoplasmic stippling in erythrocytes is a sign of irregular re- generation and often occurs nonspecifically in secondary anemia. The reticulocyte count is usually reduced in infectious or toxic anemia, un- less there is concomitant hemolysis or acute blood loss. Bone marrow analysis in secondary anemia usually shows reduced erythropoiesis and granulopoiesiswith a spectrumof immature cells (“in- fectious/toxic bone marrow”). The information is so nonspecific that usu- ally bone marrow aspiration is not performed. So long as all other labora- tory methods are employed, bone marrow cytology is very rarely needed in cases of hypochromic anemia. 135 a b c Hypochromic erythrocytes of very variable morphology indicate secondary anemia, usually in cases of infectious disease or tumor Fig. 46 Secondary anemia. a and b Erythrocyte morphology in secondary hypo- chromic anemia: the erythrocytes vary greatly in size (anisocytosis) and shape (1) (poikilocytosis), and show basophilic stippling (2). Burr cell (3), which has no spe- cific 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). 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 cy- tology 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 themost various etiologies, erythropoiesis is stimulated in a compensatory fashion, and the distribution of the markers shows the expected increase in red cell precursors. The erythro- poiesis 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 proeryth- roblasts) (for normal values, see Table 4). Usually, these red cell precursors do not show any clearly atypical morphology, but the cytoplasm is ba- sophilic even in normoblasts, accordingwith the poor hemoglobinization. Iron staining of the bonemarrow shows no sideroblasts (normoblasts con- taining 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
