Alan H. Rebar
Senior Associate Vice President for Research, Executive Director, Discovery Park, Purdue University
West Lafayette, IN, USA
Quantitative red cell data includes red cell count, hemoglobin, hematocrit, and red cell indices--mean cell volume (MCV), mean cell hemoglobin concentration (MCHC), and red cell distribution width (RDW). Total protein is also included in red cell data. Red cell count, hemoglobin, and hematocrit are all measures of red cell mass. Total protein provides information about state of hydration. Elevations of total protein most commonly result from dehydration which can also falsely elevate indicators of red cell mass.
Qualitative red cell data is red cell morphology on the blood film. In particular red cell size, shape, and color are evaluated. Variation in red cell size is anisocytosis, variation in red cell shape is poikilocytosis, variation in red cell color includes polychromasia (increased numbers of immature red cells) and hypochromasia (reduced hemoglobin in red cells).
Key red cell questions include the following:
1. Is red cell mass increased (polycythemia), decreased (anemia), or within reference intervals?
2. If decreased, is anemia regenerative or non-regenerative?
3. If regenerative, is the mechanism blood loss or hemolysis?
4. If non-regenerative can the mechanism be determined without bone marrow evaluation?
5. If red cell mass is increased, is the polycythemia relative or absolute?
6. If absolute, is the polycythemia primary or secondary?
Each of these major questions will be answered in turn in the paragraphs that follow.
Is Red Cell Mass Increased, Decreased, or Within the Reference Interval?
This question is answered simply by evaluating the indicators of red cell mass. These include red cell count, hemoglobin, and hematocrit.
If Decreased, is the Anemia Regenerative or Non-regenerative?
Evaluation of the blood film is the first step in differentiating regenerative from non-regenerative anemias. Increased numbers of polychromatophilic erythrocytes on the blood film indicates red cell regeneration. Regeneration is confirmed by doing absolute reticulocyte counts. In dogs and cats, absolute reticulocyte counts of greater than 80,000/μl indicate regeneration.
If Regenerative, is the Mechanism Blood Loss or Hemolysis?
History, signs, and physical examination are key to differentiation. Most causes of blood loss will be recognized in this way. Hemoglobinemia and/or hemoglobinuria indicate hemolysis but are not uniformly present in hemolytic conditions. Very high reticulocyte counts (>200,000/μl) are also highly suggestive of hemolysis. Whenever hemolysis is suspected, red cell morphology should be scrutinized for abnormal red cells which are characteristic of certain hemolytic disorders. These include: spherocytosis associated with immune-mediated hemolytic anemia, Heinz bodies and eccentrocytes which are associated with oxidant induced hemolysis, schistocytes associated with microangiopathic hemolysis, etiologic agents such as Mycoplasma felis, and ghost cells associated with hemolysis in general.
If Non-regenerative, Can the Mechanism be Determined Without Bone Marrow Evaluation?
Several non-regenerative anemias are characteristic enough that bone marrow evaluation is not needed to confirm the diagnosis. For example, the most common anemia of the dog and cat is the anemia of inflammatory disease. This anemia is a mild to moderate normocytic normochromic non-regenerative anemia (hematocrits as low as 30 in the dog and 25 in the cat). When such an anemia is present in conjunction with an inflammatory leukogram, additional diagnostic procedures are not necessary.
Similarly, iron deficiency anemias present with characteristic peripheral blood finding. On the blood film, red cells are smaller than normal and have pronounced areas of central pallor. Poikilocytosis and red cell fragmentation are common. Red cell indices often indicate microcytosis and hypochromasia.
Megaloblastic anemias (nuclear maturation defect anemias) often have occasional giant red cells (macrocytes) in circulation. Megaloblasts (large nucleated red cells with fully or nearly fully hemoglobinized cytoplasm but immature reticulated nuclei) may also be seen on blood films. These findings are highly suggestive of megaloblastosis but should be confirmed with bone marrow findings. The most common cause of megaloblastosis in companion animals is feline leukemia infection in cats.
Occasionally, dogs and cats with severe non-regenerative anemias also present with leukopenia and poikilocytosis characterized by dacryocytosis (tear-drop shaped erythrocytes) and ovalocytes. Platelet numbers may be elevated or reduced. These findings are suggestive of myelofibrosis but require bone marrow examination for confirmation.
Finally, occasional non-regenerative anemias characterized by large numbers (>10/100 WBC counted) of nucleated red cells on blood films in the absence of polychromasia (an inappropriate nucleated red cell response) are seen in both dogs and cats. These peripheral blood findings are indicative of bone marrow stromal damage. In dogs this is most suggestive of lead poisoning while in cats, feline leukemia virus infection is the most likely cause.
All other non-regenerative anemias have nonspecific hemogram findings and can only be further assessed via bone marrow evaluation.
If Red Cell Mass is Increased, is Polycythemia Relative or Absolute?
Relative polycythemia (due to dehydration) is by far the most common form of polycythemia. It is characterized by increased red cell mass and total protein as well as serum chemical indicators of dehydration (increased sodium, potassium, chloride, total protein and albumin). When relative polycythemia is ruled out, the remaining cases are absolute polycythemias.
If Absolute, is Polycythemia Primary or Secondary?
Secondary polycythemia is associated with a variety of underlying conditions. These include cardiovascular disease (reduced tissue oxygenation), pulmonary disease (reduced oxygen delivery to red cells and therefore tissues), renal disease (primarily renal neoplasms which can cause increased erythropoietin levels), and Cushing's disease (increased androgen production results in increased red cell production). When these potential causes are ruled out, polycythemia is suspected to be primary.
Primary polycythemia is due to the myeloproliferative disorder polycythemia vera. Polycythemia vera is characterized by normal circulating erythropoietin levels and normal tissue oxygenation (normal arterial blood gas) with significant increases in red cell mass (hematocrits 65 or greater). Bone marrow findings may be normal or indicate red ell hyperplasia.