In this section, the following will be covered:
- Overview of anemia (see below) with examples of how indices and severity can help us identify the mechanism and cause of anemia.
- Assessment of regeneration
- Mechanisms of anemia
- Causes of anemia
- Anemia summary: Summary of the mechanisms and causes (not exhaustive) of anemia.
Anemia is defined as a decreased hematocrit (HCT) or hemoglobin. Packed cell volume (PCV), which is readily measured in clinical practice, can be used as a surrogate for hematocrit (a calculated value from the mean cell volume and red blood cell [RBC] count) and hemoglobin concentration, which are provided by automated analyzers. Note, that splenic relaxation (anesthetic agents, tranquilizers) can result in an apparent anemia due to sequestration of RBC in the spleen (up to 30% of RBC may be sequestered in the spleen). Also, young animals frequently have a physiologic anemia (due to rapid growth rate with hemodilution from plasma volume expansion, dilutional from ingested colostrum, destruction of fetal RBC, decreased production due to low erythropoietin concentrations) in the first few months of life (generally < 4 months old).
In general terms, anemia is characterized by severity, RBC indices and regenerative response. This characterization is useful in helping to determine the mechanism and cause of an anemia.
- Severity: This is determined by the degree of decrease in the HCT and will vary between species, depending on the lower limit of a the reference interval. Guidelines on severity of the anemia in the dog and cat are given below. These guidelines are arbitrary and subjective. In other species, a HCT <15% is considered a severe anemia. Severity can help rule in or out a specific cause of anemia. For instance, a severe anemia should not be attributed alone to anemia of inflammatory disease, which typically only causes a mild to moderate non-regenerative anemia. However, inflammatory disease combined with hemorrhage or hemolysis may manifest as a severe anemia.
|Grade of anemia||Canine||Feline|
|None (reference interval)||41-58||31-48|
- Red blood cell indices: RBC indices include mean corpuscular volume (MCV) and mean corpuscular hemoglobin concentration (MCHC). This allows categorization of an anemia on the basis of cell volume and hemoglobin concentration. Changes in RBC indices also provide clues as to the cause of the anemia, e.g. microcytic hypochromic anemias (regenerative or not) are often due to iron deficiency (see RBC indices interpretation).
- Macrocytic: MCV above the reference interval.
- Normocytic: MCV within the reference interval.
- Microcytic: MCV below the reference interval.
- Hyperchromic: MCHC above the reference interval. Usually a false increase (not a true in vivo finding), e.g. lipemia can falsely increase the hemoglobin concentration relative to the HCT, thus falsely increasing the MCHC.
- Normochromic: MCHC within the reference interval.
- Hypochromic: MCHC below the reference interval
- Regenerative response: Assessment of regeneration is the very first step in evaluating an anemia. If an anemia is regenerative, it is due to hemorrhage or hemolysis. However, if the anemia is non-regenerative, then decreased bone marrow production is causing the anemia, although hemorrhage or hemolysis could also be occurring. Remember that the bone marrow takes 3 to 5 days to respond to an anemia, therefore an acute hemorrhagic or hemolytic anemia may initially appear non-regenerative. In such cases, evidence of regeneration should become apparent within 4-5 days.
There are also species differences in the regenerative response. In general, to determine if an animal is responding to an anemia, we usually examine a blood smear for the presence of immature anucleate RBC, i.e. polychromatophils. This works for most species, except equidae who do not usually release polychromatophils into the circulation (but do release macrocytes). In dogs and cats, we can also quantify the regenerative response by counting reticulocytes. Because immature anucleate RBC are frequently larger and contain less hemoglobin than mature RBC, a regenerative anemia may have macrocytic (high MCV) hypochromic (low MCHC) RBC indices and a high red blood cell distribution width (RDW). The RDW is an electronic measurement of the variation in RBC volume or the electronic equivalent of anisocytosis on a blood smear, thus a high RDW indicates more variation than normal (in a regenerative anemia, this is usually due to the presence of larger RBC than normal). However if these changes are not present on a hemogram, they do not rule out a regenerative response. Conversely, a high MCV, low MCHC, and high RDW can be seen in causes other than a regenerative anemia, so their presence on a hemogram does not indicate regeneration. Rather, evaluation of a blood smear for immature anucleate RBC (and quantifying reticulocytes in dogs and cats) is key in determining if an anemia is regenerative or not. A recent study has shown that less than a third of regenerative anemias in dogs and cats are characterized by macrocytic hypochromic RBC, confirming that these features should not be relied upon.
Other features that may be seen in blood smears of animals with a regenerative response but are not specific for regeneration alone (they can occur as a consequence of other conditions or diseases) are:
- Anisocytosis: Variation in RBC size occurs because immature anucleate RBC are usually larger than mature RBC
- Increased numbers of nRBC
- Basophilic stippling: These are blue dots in the cytoplasm of RBC in routinely stained blood smears, which correspond to aggregates of ribosomes and polyribosomes. This is especially seen in ruminants but can also be seen in dogs and cats.
- Increased numbers of RBC containing Howell-Jolly bodies (remnants of the nucleus).
- RBC indices interpretation: How RBC indices help identify mechanism (and potential cause) of an anemia