The anemias. Normocytic normochromic anemias

The term normocytic normochromic anemia is applied to those forms of anemia in which the mean size and hemoglobin content of the red cells are within normal limits. Usually microscopic examination of the red cells shows them to be much like normal cells. In other cases there may be marked variations in size and shape, but these are such as to equalize one another, thus resulting in normal mean values. The normocytic anemias are a miscellaneous group, by no means as homogeneous as the megaloblastic anemias.

Anemia caused by the sudden loss of blood is necessarily normocytic at first, since the cells that remain in the circulation are normal. The blood loss stimulates increased production, and the young cells that enter the blood in response are larger than those already present in the blood. If the young cells are present in sufficient number, the anemia temporarily becomes macrocytic (but not megaloblastic).

The many causes of acute blood loss include trauma, peptic ulceration of the stomach or bowel, and ulcerative lesions of other types. Treatment includes replacement, by transfusion,of the blood lost and appropriate steps directed against the cause.

A common form of anemia is that occurring in association with various chronic infections and in a variety of chronic systemic diseases. As a rule the anemia is not severe, although the anemia associated with chronic renal insufficiency (defective functioning of the kidneys) may be extremely so. Most normocytic anemias appear to be the result of impaired production of red cells, and in renal failure there is a deficiency of erythropoietin, the factor inthe body that normally stimulates red cell production. In these states, the life span of the red cell in the circulation may be slightly shortened, but the mechanism of production of the anemia is failure of red cell production. The anemia of chronic disorders is characterized by abnormally low levels of iron in the plasma in the face of excessive quantities in the reticuloendothelial cells (cells whose function is ingestion and destruction of other cells and of foreign particles) of the bone marrow. Successful treatment depends on the possibility of eliminating or relieving the underlying disorder.

The mild anemias associated with deficiencies of the anterior pituitary, thyroid, adrenocortical, and testicular hormones usually are normocytic. As in the case of anemia associated with chronic infections or various systemic diseases, the symptoms usually are those of the underlying condition, although sometimes anemia may be the most prominent sign. Unless complicated by deficiencies of vitamin B12 or iron, these anemias are abolished by appropriate treatment with the lacking hormone.

Invasion of bone marrow by cancer cells carried by the bloodstream, if sufficiently great, is accompanied by anemia, usually normocytic in type but associated with abnormalities of both red and white cells. It is thought that such anemia is due to impaired production of red cells through mechanical interference. Whether this is true or not, a characteristic sign in the peripheral blood is the appearance of many irregularities in the size and shape of the red cells and of nucleated red cells; these young cells normally never leave the bone marrow but appear when the marrow's structure is distorted by invading cells.

In aplastic anemia the normally red marrow becomes fatty and yellow and fails to form enough of its three cellular products—red cells, white cells, and platelets. Anemia with few or no reticulocytes, reduced levels of the types of leukocytes formed in the bone marrow (granulocytes), and reduced platelets in the blood are characteristic. Manifestations of aplastic anemia are related to these deficiencies and include weakness, increased susceptibility to infections, and bleeding manifestations. In some cases the onset of aplastic anemia has been found to have been preceded by exposure to such organic chemicals as benzol, insecticides, or a variety of drugs, including especially the antibiotic chloramphenicol. While it is well established that certain agents may produce aplastic anemia, most persons exposed to these agents do not develop the disease and most persons with aplastic anemia have no clear history of exposure to such agents. There are other agentsthat produce aplasia in a predictable way. These include some of the chemotherapeutic agents used in the treatment of cancer, lymphoma, and leukemia, as well as irradiation treatment for these diseases. Because of this fact, blood counts are frequently checked anddoses of drugs or irradiation modified in patients being treated. Withdrawal of medication is followed by recovery of the bone marrow in such cases. On the other hand, in those patients who develop aplastic anemia as a result of exposure to other toxic agents, cessation of exposure may not result in recovery of the marrow, or at best the marrow may be indolent andincomplete.

Treatment of aplastic anemia is a twofold process. First, the patient must be supported through complications of the disease: infection calls for vigorous treatment with antibiotics; symptoms due to anemia call for red cell transfusions; bleeding calls for platelets. Second, efforts should be directed toward inducing bone marrow recovery. Based on the hypothesis that one of the mechanisms of production of the aplasia is autoimmunity, medication to suppress the immune response, such as the administration of antithymocyte globulin, is occasionally successful. An important and effective treatment is transplantation of bone marrow from a normal, compatible donor, usually a sibling. This treatment is limited by the availability of compatible donors and also by the fact that the recipient is increasingly prone to serious complications with advancing age.