CAP TODAY Pathology/Laboratory Medicine/Laboratory Management
Karen Titus
December 2014—Anemia is in the eye of the classifier. While that’s not as elegant as the “beauty-beholder” saying, it’s much more important. To be able to effectively treat and diagnose anemia, “You have to know what is causing the decrease in red cells,” said Sherrie Perkins, MD, PhD, speaking at an AACC workshop this year.
There are plenty of definitions to choose from, said Dr. Perkins, of the University of Utah/ARUP Laboratories, Salt Lake City. At the most basic level, she noted, anemia is a pathologic condition marked by a reduced capacity of blood to transport and deliver adequate oxygen to tissues. In short, anemia is a manifestation of disease, not a disease itself.
Dr. Perkins
The most common CBC parameters used to establish anemia include hemoglobin concentration, hematocrit, red blood cell concentration, and mean corpuscular hemoglobin. “That will give us some very good information,” but it’s far from perfect, she said, since hemoglobin concentration and hematocrit utility may be affected by altered plasma volumes, chronic oxygenation status, and hemoglobin variants/hemoglobinopathies.
The NHANES definition uses the lower limit of normal adult hemoglobin (from 10 to 44 years): 13.2 g/dL in men, 11.7 g/dL in women. The WHO, relying on a technique common among checkbook balancers, “tends to round to make things a little bit easier” and bases its definition on 13.0 g/dL in men and 12.0 g/dL in women. Beyond this, Dr. Perkins said, it’s well understood that acceptable levels are lower in children and in women during pregnancy; the African-American population also tends to have slightly lower (0.5 to 0.6 g/dL) values. Men tend to have slightly higher hematocrit levels than women—also considered to be “completely normal,” she said.
Anemia is dependent on the RBC lifespan. To understand it, “We have to know where the red cells come from.” Under normal conditions, bone marrow erythroid production is constant. The normal 70-kg adult RBC mass is about 2,000 mL, or 300 × 109 RBCs/kg. The normal RBC lifespan is 100 to 120 days, so any alterations that affect RBC production or lifespan may cause anemia. Replenishment requires adequate bone marrow hematopoietic pools, nutrients, and stimulation of proliferation by factors such as erythropoietin.
On a practical level, the various definitions and symptoms create an interesting classification challenge. Historically, noted Dr. Perkins, people used CBC data and red cell morphology, primarily the mean corpuscular volume (i.e. RBC size). Under this scheme, anemias were determined to be microcytic (95 fL). This remains a common diagnostic approach because it provides useful pathophysiologic insights.
Another useful way to think about anemia classification is pathogenetically. Anemias can occur because of impaired proliferation or maturation. This could be related to the bone marrow, such as in diseases like aplastic anemia or myelodysplastic syndromes. Tumors can also cause bone marrow infiltration, leading to less bone marrow capacity for red cell production. Other possible culprits include vitamin deficiencies; marrow suppression from drugs, radiation, or infections; and chronic disease/inflammation.
On the other hand, anemia can be caused by increased destruction (i.e. hemolysis) of red cells. Shortened RBC lifespan often results from inherent abnormalities of the red cells, such as membrane or enzyme defects. It can also be caused by hemoglobinopathies, immune-based hemolytic anemia, infections of red cells (e.g. malaria), or splenic removal. Finally, there’s plain old blood loss.
Dr. Perkins divided pathogenetic classification into three basic categories: