Heme/Onc: understanding anemia

When admitted to the hospital almost all patients will receive a standard battery of blood tests, which includes a Complete Blood Count (CBC).  Often a primary care office will order such work for their patients simply to have a baseline, and many specialists will do so as a means to monitor drug reactions and overall health.  A CBC includes the measurement of many different components of blood, including the number of red blood cells, white blood cells, platelets, hemoglobin, hematocrit, and mean corpuscular volume.  The shorthand of the CBC looks like this:

On the left is the number of white blood cells; on the right- platelets; the H & H is in the middle, referring to the hemoglobin and hematocrit, with the hemoglobin on top.  For anemia the Hemoglobin (Hgb) matters most.  While it doesn't appear in the shorthand form of the CBC, the Mean Corpuscular Volume (MCV) also matters since it allows for an easy classification of anemia.  

Anemia results from a decreased oxygen delivery by the blood.  Symptoms can include many different manifestations including fatigue, lethargy, cold intolerance, and even passing out!  Anyone can address the symptoms, but only in knowing the type and cause of the anemia can one hope for an overall cure.  This does not mean that the anemia can't self resolve.  Many people may become transiently anemic yet never know it, but if seeking medical attention the patient will want as much information as possible.  

Mean Corpuscular Volume refers to the average red blood cell volume.  An anemia will very often affect this number thus allowing for a very simple classification, based on whether the number occurs within normal limits.  The normal value for an MCV ranges between 80 - 100.  The system of classification is as follows:

• Normocytic: MCV between 80 - 100
• Microcytic: MCV less than 80
• Macrocytic: MCV greater than 100

Knowing the type of anemia starts the search for a cause, but in no way gives a definitive answer on its own.  But at least you can sound smart by beginning with a classification of the anemia.  

Microcytic anemias, those with an MCV below 80, often have red blood cells which look pale compared to normal--a phenomenon known as hypochromasia.  Numerous causes exist for a microcytic anemia, but keep in mind that while a microcytic state may point in one direction it is still important to consider causes which typically present as normocytic or macrocytic.  That said, the most typical causes include: 

• Iron deficiency
• Thalassemia
• Sideroblastic anemia
• Anemia of chronic disease

To understand the entities which compromise microcytic anemias requires an understanding of hemoglobin--the oxygen carrying compound in red blood cells.  Hemoglobin has two components:

• Heme: the iron containing molecule of hemoglobin
• Globin chains: four subunit chains defined as either alpha, beta, gamma, or delta

These components must come together correctly in order to have a properly functioning hemoglobin.  While iron deficiency affects heme, it is thalassemia which affects the globin chains.  Thalassemia results from a genetic mutation affecting the formation of the globin chains.  Normal adult hemoglobin has two alpha and two beta chains, and normal fetal hemoglobin has two alpha and two gamma chains; the condition is named for the chain it affects.  Thus alpha thalassemia affects the formation of the alpha chain, and so on.  

One must also understand sideroblastic anemia, a condition which results when the bone marrow makes ringed sideroblasts rather than typical red blood cells.  While it sounds confusing just understand that ringed sideroblasts are basically red blood cells which have nuclei as well as iron deposits.  Any number of things can cause a sideroblastic anemia, but four particular causes to know:

• Alcohol
• Pyridoxine deficiency
• Lead poisoning
• Myelodysplasia

A prussian blue stain, which will pick up the iron, may appear as follows:

Normocytic anemias occur within the normal limits of the MCV value.  Again keep in mind that causes between the different anemias may overlap:

• Aplastic anemia
• Sideroblastic anemia
• Anemia of chronic disease
• Fluid overload

Aplastic anemia occurs when the bone marrow does not respond adequately to the need for new RBC production.  To measure this look at the reticulocyte count, which is normally less than 2.  During times in which the bone marrow must make new RBCs the reticulocyte count should rise above 2, if it does not consider that the bone marrow has not appropriately responded to the stimulus for more production.  

Macrocytic anemias occur when the MCV has surpassed 100.  When thinking of this type of anemia think of diet induced.  Although not always true it covers the three most important causes:

• Vitamin B12 deficiency
• Folate deficiency
• Alcohol

Thus comes the biggest question: how does one evaluate an anemia after looking at the MCV?  

Simple: order more tests!  

Absolutely standard tests for anemia should include a measure of serum iron, a ferritin level, and the calculated Total Iron Binding Capacity (TIBC), as well as a Serum Protein Electro Phoresis (SPEP), Urine Protein Electro Phoresis (UPEP), and a level of B12 and folate.  

Other tests to order may include a Lactate DeHydrogenase (LDH), which is released during cell destruction and serves as a particularly useful marker for RBC destruction.  

I can go into further detail if anyone would want that.  Just message me.  In the meantime I find an interesting article, which I have cited, in the AMA's Archives of Internal Medicine.  Written in 1958, it describes the clinical application of SPEP, something taken for granted today.  You may find it a waste of time to read, but it is interesting to see how science has progressed!

 

Robert Wall (1958). The Use of Serum Protein Electrophoresis in Clinical Medicine Archives of Internal Medicine, 618-658