F.A. Rice, ART, CLS March 1, 1996 Please send comments to: F.A. Rice
A great deal of the work in a hematology department is directed to the study of patients with anemia. Anemia can be defined as a reduction in the hemoglobin, hematocrit or red cell number. In physiologic terms an anemia is any disorder in which the patient suffers from tissue hypoxia due to decreased oxygen carrying capacity of the blood. It is therefore possible for a patient to be physiologically anemic and still have a normal or even raised hemoglobin, hematocrit and or red cell number, this is referred to as a relative anemia. We usually use the term "anemia" to refer to an absolute anemia, ie a reduction in red cell or hemoglobin mass.
A review of the normal components of blood and hemopoiesis in general is available here. To review the identification of normal peripheral blood cells click here. Note, this site may take several minutes to load. A set of review slides is available here.
Anemia is usually classified according to:
1. ETIOLOGIC This is classification by cause. An anemia may be due to blood loss which may be due to many causes, eg. excessive vaginal bleeding due to functional menorrhagia, malignancy or endometriosis. 2. PATHOPHYSIOLOGIC This classification is based on the actual red cell defect ie decreased red cell production or increased red cell destruction. In other words the anemia can be classified as:
In many cases both defects are operative or there is uncertainty as to the exact defect which is operative. 3. MORPHOLOGIC This is a classification based on cell size and color. This classification is usually used in the laboratory as we actually see the cells. It is not entirely satisfactory as an anemia due to chronic bleeding may be normocytic at one point, microcytic later and microcytic hypochromic even later. In fact the most often used classification system is a combination of the pathophysiologic and morphologic.
MORPHOLOGIC CLASSIFICATION
1. Macrocytic Anemia The macrocytic anemias may be further subdivided based upon the degree to which the MCV is raised and the presence of megaloblastic production in the bone marrow. slight increase in MCV: MCV >100 and <105 fl - due to the presence of retics - in some instances of aplastic anemia - myxedema In all cases the red cell precursors in the marrow are normal in morphology. moderate increase in the MCV: MCV >105 and <110 fl - liver disease marked increase in the MCV: MCV > 110 fl - megaloblastic due to the lack of vitamin B-12 or folic acid. 2. Normocytic Anemia These are due to either an increased rate of red cell destruction or a failure in red cell production. The presence of specific poikilocytes are often diagnostic.
3. Microcytic Anemia These are associated with an inability to produce hemoglobin. Hemoglobin consists of iron inserted into the prtoporphyrin ring complex to form heme which in turn is inserted into the globin chain. Hence these anemias are seen in:
For Tom DeLoughery' excellent review of anemia click here.
The pathophysiologic effects of anemia depend upon the rate at which the anemia progresses. In an acute hemorrhage the arterial pressure falls, cardiac output decreases, peripheral vasculature collapses and the patient rapidly enters hypovolemic shock. The sudden, rapid loss of 30% of the total blood volume often results in death unless there is immediate medical intervention. In a slowly developing anemia cardiac output increases, blood is shunted from non vital organs and hemoglobin oxygen affinity decreases due to increased levels of 2-3-DPG and the Bohr effect. Total blood volume remains remarkably constant. More than 50% of the red cell mass can be lost slowly with minimal effect. It must be remembered that anemia is NOT a disease, rather it is a sign of disease. The clinical effects include tiredness, lassitude, weakness, pallor and perhaps pyrexia and shock. Dyspnea and anginal pain are not uncommon after exercise. Jaundice may occur in some anemias.
In most laboratories the initial investigation and tentative diagnosis is made with a relatively small number of tests. The precise diagnosis is made with further special tests. Screening is usually done with the CBC or "complete blood count". The exact procedures in a CBC depends upon the instrumentation in the laboratory. Most laboratories now use automated, multiparameter instruments which will provide results for the following parameters:
A stained blood film should be examined whenever any of the above parameters are abnormal. Examination of the blood film can identify a large range of erythrocyte, leukocyte and thrombocyte changes. The presence of red cell inclusions indicates abnormal erythropoiesis or an increased rate of red cell destruction while poikilocytes indicate a severe red cell abnormality. In some instances poikilocytes can suggest a specific diagnosis. Changes in leukocytes and platelets can provide a clue as to the etiology of an anemia. Some of these changes will be detected by current automated instrumentation. Once a tentative diagnosis is made special tests can be performed to confirm the diagnosis. These include iron studies, vitamin studies, hemoglobin studies, enzyme levels, bone marrow aspirate or biopsy, red cell survival studies etc.