Hyperchromic Anemias

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In patients with clear signs of anemia, e.g., a "sickly pallor," atrophic lingual mucosa, and sometimes also neurological signs of bathyanesthesia (loss of deep sensibility), even just a cursory examination of the blood smear may indicate the diagnosis. Marked poikilocytosis and anisocytosis are seen, and the large size of the erythrocytes is particularly conspicuous in comparison with the lymphocytes, whose diameter they exceed (mega-locytes). These are the hallmarks of macrocytic, and, with respect to bone marrow cells, usually also megaloblastic anemia, with a mean cell diameter greater than 8 ^m and a cell volume (MCV) usually greater than 100^m3. Mean cell Hb content (MCH) is more than 36 pg (1.99 fmol) and thus indicates hyperchromic anemia.

Only when there is severe pre-existing concomitant iron deficiency is a combination of macrocytic cells and hypochromic MCH possible ("dimorphic anemia").

Table 26 Most common causes of hyperchromic anemias

Vitamin-B12 deficiency

Folic acid deficiency

Nutritional deficits, e.g.

Nutritional deficits

- Goat milk

- Chronic abuse of alcohol

- Vegetarian diet

- Alcoholism

Impaired absorption

Impaired absorption

- Genuine pernicious anemia

- E. g., sprue (psilosis)

- Status after gastrectomy

- Ileum resection

Increased requirement

- Crohn disease

- Pregnancy

- Celiac disease, sprue (psilosis)

- Hemolytic anemia

- Intestinal diverticulosis

Interference/antagonism

- Insufficiency of the exocrine pancreas

- Phenylhydantoin

- Fish tapeworm

- Cytostatic antimetabolic drugs

- Trimethoprim (antibacterial combination drug)

- Oral contrazeptives

- Antidepressants

- Alcohol

Although other rare causes exist (Table 26), almost all patients with hyperchromic anemia suffer from vitamin B12 and/or folic acid deficiency. Since a deficiency of these essential metabolic building blocks suppresses DNA synthesis not only in erythropoiesis, but in the other cell series as well, over time more or less severe pancytopenia will develop.

Conspicuous large erythrocytes suggest hyperchromic macrocytic anemia, usually megaloblastic in the bone marrow a c

Vacuolization Alcohol Erythroblasts

Fig. 53 Hyperchromic anemia. a Marked anisocytosis. In addition to normal-sized erythrocytes (1), macrocytes (2) and large ovoid megalocytes are seen (3). Hypersegmented granulocyte (4). b In hyperchromic anemia, red cell precursors may be released into the peripheral blood: here, a polychromatic erythroblast. c and d Bone marrow in megaloblastic anemia: slight (1) or marked (2) loosening up of the nuclear structure, in some cases with binuclearity (3). Giant forms of band granulocytes and metamyelocytes (4) are often present.

Fig. 53 Hyperchromic anemia. a Marked anisocytosis. In addition to normal-sized erythrocytes (1), macrocytes (2) and large ovoid megalocytes are seen (3). Hypersegmented granulocyte (4). b In hyperchromic anemia, red cell precursors may be released into the peripheral blood: here, a polychromatic erythroblast. c and d Bone marrow in megaloblastic anemia: slight (1) or marked (2) loosening up of the nuclear structure, in some cases with binuclearity (3). Giant forms of band granulocytes and metamyelocytes (4) are often present.

With hypersegmentation, i.e. > 4-5 segments/nucleus, the segmented granulocytes show all the indications of a maturation disorder. In addition, the reticulocyte count is increased (but it may also be normal), and the iron content is elevated or normal.

Megaloblastic anemias show the same hematological picture whether they are caused by folic acid deficiency or by vitamin B12 deficiency.

Table 26 lists possible causes. It should be emphasized that "genuine" pernicious anemia is less common than megaloblastic anemia due to vitamin B12 deficiency. In pernicious anemia a stomach biopsy shows atrophic gastritis and usually also serum antibodies to parietal cells and intrinsic factor.

Among the causes of folic acid deficiency is chronic alcoholism (with insufficient dietary folic acid, impaired absorption, and elevated erythrocyte turnover). On the other hand, many alcoholics with normal vitamin B12 and folic acid levels develop severe hyperchromic anemia with a special bone marrow morphology, obviously with a pathomechanism of its own (pyridoxine [Be] deficiency, among others).

In megaloblastic anemia (Fig. 53) the cell density in the bone marrow is always remarkably high. Large to medium-sized blasts with round nuclei dominate the erythrocyte series. They are present in varying sizes, their chromatin is loosely arranged with a coarse "sandy" reticular structure, there are well-defined nucleoli, and the cytoplasm is very basophilic with a perinuclear lighter zone. These cells can be interpreted as proerythroblasts and macroblasts whose maturation has been disturbed. As these disturbed megaloblastic cells appear along a continuous spectrum from the less mature to the more mature, they are all referred to collectively as megaloblasts.

In the granylocytic series, anomalies become obvious at the myelocyte stage; characteristic giant cells with loosely structured nuclei develop which may tend to be classified as myelocytes/stab cells, but which in fact probably are myelocytes in which the maturation process has been disturbed. As in peripheral blood smears, segmented granulocytes are often hypersegmented. Megakaryocytes also show hypersegmentation of their nuclei or many individual nuclei. Iron staining reveals increased number of iron-containing reticular cells and sideroblasts, and a few ring sidero-blasts may develop. All these changes disappear after vitamin B12 supplementation, after just three days in the erythrocyte series and within one week in the granulocyte series. In the differential diagnosis, in relation to the causes listed in Table 26, the following should be highlighted: toxic alcohol damage (vacuolized proerythroblasts), hemolytic anemia (elevated reticulocyte count), myelodysplasia (for bone marrow morphology see Fig.37, p. 109).

In older patients, myelodysplastic syndrome should be the first item in the differential diagnosis of hyperchromic anemias a

Myelodysplastic Syndrome Bone Marrow

Fig. 54 Myelodysplastic syndrome (MDS) as differential diagnosis in hyperchromic anemia. a Strongly basophilic stippling in the cytoplasm of a macrocyte (in myelodysplasia). b Myeloblast with hyperchromic erythrocyte as an example of a myelodysplastic blood sample in the differential diagnosis versus hyperchromic anemia. c A high proportion of reticulocytes speaks against megaloblastic anemia and for hemolysis (in this case with an absence of pyruvate kinase activity). d Bone marrow in myelodysplasia (type RAEB), with clinical hyperchromic anemia.

Fig. 54 Myelodysplastic syndrome (MDS) as differential diagnosis in hyperchromic anemia. a Strongly basophilic stippling in the cytoplasm of a macrocyte (in myelodysplasia). b Myeloblast with hyperchromic erythrocyte as an example of a myelodysplastic blood sample in the differential diagnosis versus hyperchromic anemia. c A high proportion of reticulocytes speaks against megaloblastic anemia and for hemolysis (in this case with an absence of pyruvate kinase activity). d Bone marrow in myelodysplasia (type RAEB), with clinical hyperchromic anemia.

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Responses

  • Tiblets
    What causes hyperchromic rbc?
    8 years ago
  • nebay
    What are hyperchromic megakaryocytes?
    7 years ago
  • agatino
    Is there hyperchromic anemia?
    7 years ago
  • birikti ambessa
    What is hyperchromatic and clustering forms?
    7 years ago
  • askalu
    What anemias are hyperchromic?
    7 years ago
  • Faramir Lightfoot
    Why do rbc in megaloblaatic anemia appear hyperchromic?
    3 years ago
  • kayla
    What is hyperchronic in kidiney?
    3 years ago
  • antonino
    Why hyperchromic anaemia is not possible?
    2 years ago
  • RUTA
    What is mycrocytic hyperchromic anaemia?
    2 years ago
  • patrick
    How does folate lead to hyperchromic anemia?
    2 years ago
  • tewelde
    Why are erythrocytes macrocytic in pernicious anemia?
    9 months ago
  • marco finkel
    What can cause hyperchromic red cells?
    9 months ago
  • segan massawa
    Is MCH diagnostic for hyperchromic anemia?
    6 months ago
  • Brayden
    What causes hyperchromatism?
    2 months ago
  • Eric
    Why mchc in not hyperchromic?
    5 days ago

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