The Microcytic Anemias



F.A. Rice,  ART, CLS  
March 1, 1996
Please send comments to: F.A. Rice


Outline:

 

	


DEFINITION of ANEMIA

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.


CLASSIFICATION of ANEMIA

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.


PHYSIOLOGIC EFFECTS of ANEMIA

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.


LABORATORY DIAGNOSIS of ANEMIA

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.

LABORATORY ERRORS