Anaemia is a common clinical and laboratory finding, which in itself does not constitute a diagnosis. It is an absolute decrease in erythrocyte numbers in the body, reflected in a decrease in haematocrit (HCT), haemoglobin concentration (Hgb), and red blood cell count (RBC). A relative anaemia occurs with an increase in plasma volume (overhydration). The major significance of anaemia is decreased oxygen-carrying capacity to tissues. When the anaemia develops suddenly, the body does not have time to adjust and a relatively small decrease in red cell mass will result in severe clinical signs. When the anaemia develops over a longer time period, the body has time to adjust and can cope better with the anaemia. Clinical signs associated with anaemia reflect the decreased oxygen-carrying capacity and include exercise intolerance, weakness, depression, and tachypnoea.

There are 3 common classification systems for anaemia:

Morphologic Classification Using Erythrocyte Indices

This system is based on erythrocyte volume (mean corpuscular volume; MCV) and haemoglobin concentration (mean corpuscular haemoglobin concentration; MCHC), as well as the examination of erythrocytes on a Wright-stained blood smear. MCV is the volume per average erythrocyte and expressed in femtoliters. MCHC (or CHCM) is the cellular 'Hgb' per average erythrocyte expressed as g/dL. In most blood samples, not all erythrocytes are the same, and it is therefore important to remember that the MCV and MCHC represent the averages for all erythrocytes in the sample. MCV, together with [RBC], is used to calculate HCT, and in turn MCHC is calculated from the measured blood [Hgb] and calculated HCT.

MCV and MCHC (or CHCM) suggest the type of erythrocyte that is being produced by the marrow of the anaemic patient:

 Normocytic - erythroid cell maturation not defective

 Macrocytic - presence of young erythrocytes; defective erythrocyte maturation

 Microcytic - mitosis during erythropoiesis may create smaller cells

 Normochromic - Hgb synthesis is complete

 Hypochromic - Hgb synthesis is incomplete (reticulocytes or defective synthesis)

 Hyperchromic - erythrocytes were not hyperchromic when produced; either they lost volume (in vivo or in vitro) or there is an erroneous MCHC (haemolysis)

Because MCV and MCHC are averages, blood smear examination is a more sensitive method of detecting macrocytic, microcytic, and hypochromic cells.

The red cell distribution width (RDW) is a calculated value (expressed as %) that reflects the amount of variation in erythrocyte volume (anisocytosis). The RDW may therefore be an early indicator of a change in erythrocyte volume before it is reflected by MCV.

Normocytic Normochromic Anaemias

Most anaemias begin as normocytic normochromic, until the marrow releases sufficient larger or smaller erythrocytes with normal or decreased Hgb. Persistent normocytic normochromic anaemias are considered nonregenerative.

Macrocytic Hypochromic Anaemias

Concurrent macrocytosis and hypochromasia support the presence of immature erythrocytes and one can expect to see polychromasia on the blood smear. Anaemia is probably due to blood loss or haemolysis. As previously mentioned, HCT is calculated from measured MCV and [RBC], and MCHC is a calculation of [Hgb] and HCT. Thus, if MCV is falsely increased, then the calculated MCHC will be falsely decreased.

Macrocytic Normochromic Anaemias

Common with regenerative anaemias due to blood loss or haemolysis. Can also be associated with defective erythropoiesis (e.g., FeLV infection, folic acid and cobalamine deficiencies, poodles with poodle marrow dyscrasia, and erythroleukemia). The MCV may also be increased due to certain sample or patient conditions such as erythrocyte agglutination, cell swelling during storage before testing, in vivo hyperosmolar states (e.g., hypernatraemia) leading to increased intracellular osmolality, and excess dipotassium-EDTA anticoagulant resulting in erythrocyte swelling.

Microcytic Hypochromic Anaemias

Typically due to defective Hgb production caused by iron deficiency (copper and vitamin B6 deficiencies have also been implicated).

Microcytic Normochromic Anaemias

Early or mild iron deficiency prior to causing a microcytic hypochromic anaemia; hepatic failure due to hepatic disease or portosystemic shunts (most likely due to defective iron transport to erythrocyte precursors); dyserythropoiesis in English springer spaniels; and seen as a normal finding in some dog breeds (e.g., Akitas, Shibas, and other Asian breeds).

Normocytic Hypochromic Anaemias

Very uncommon, but may be seen when erythrocytes are hypochromic and the MCV has not changed enough to be outside the reference interval.

Macrocytic (or Normocytic) Hyperchromic Anaemias

Typically, the MCHC is falsely increased, most likely due to in vivo or in vitro haemolysis or spectral interference during measurement of Hgb by lipid droplets (lipaemic samples), pigments in markedly icteric samples, and Heinz bodies, etc.

Microcytic Hyperchromic Anaemias

False low MCV and high MCHC may be seen when erythrocytes are in hypo-osmolar plasma (e.g., hyponatraemia and hypochloraemia).

Classification by Marrow Responsiveness

This classification is primarily based on the presence or absence of reticulocytes in blood. There are 3 common methods of enumerating blood reticulocytes:

 Reticulocyte concentration/absolute reticulocyte count (ARC) - concentration of reticulocytes in blood expressed as the number/µL (or L). This is the preferred method for evaluating marrow response to anaemia.

 Reticulocyte percentage (RP) - percentage of erythrocytes that are reticulocytes in a blood sample. Does not take into account the HCT of the patient.

 Reticulocyte production index (RPI) - with increasing severity of anaemia, reticulocytes spend less time maturing in the marrow and more time in circulation before maturing; therefore the reticulocyte percentage may be increased because of increased life span and not necessarily increased production. Application of RPI requires that erythrocyte maturation times are known for species during normal and accelerated erythropoiesis. Therefore, it is recommended to use ARC to assess regenerative status.

Absolute increase in reticulocytes indicates a responding bone marrow (regenerative anaemia) and that the cause of the anaemia is extra-marrow (i.e., blood loss or haemolysis). An ARC > 60 cells/L in the dog and > 40 cells/L in the cat indicates a regenerative response. Reticulocytosis is more intense in haemolytic anaemias - iron from disrupted erythrocytes is more readily available for erythropoiesis than iron stored as haemosiderin. Reticulocytosis does not become clearly evident until 48 to 72 hours after the occurrence of anaemia. Dogs have a greater reticulocyte response than cats. Lack of reticulocyte response (nonregenerative anaemia) may be due to insufficient time for reticulocytosis to occur, a deficiency in the existing reticulocyte response, or defective erythropoiesis. Most nonregenerative anaemias are normocytic normochromic without poikilocytosis or other erythrocyte abnormalities.

Pathophysiologic Classification

This classification is based on the underlying pathologic mechanism or process that produced the anaemia. This classification system is frequently used as a differential diagnosis list or to group specific diseases based on the method or methods by which they cause anaemia.

Multiple pathologic processes may contribute to anaemia

 Blood loss anaemia

 Acute (hours to days) - The HCT often does not reflect the severity of the process with peracute blood loss. Compensatory fluid shifts take several hours to occur.

 Chronic (weeks to months) - The anaemia occurs mainly as a result of iron deficiency that develops and not the amount of blood lost. Once iron deficiency is present, erythrocyte regeneration is impaired.

 External - Erythrocytes are lost from body or into the urinary or intestinal tract.

 Internal - Erythrocytes move from the intravascular to the extravascular space (peritoneal or pleural cavities).

 Haemolytic anaemia

 Intravascular haemolysis - Erythrocyte destruction occurs in the blood within the blood vessels and is clinically recognised by haemoglobinaemia and haemoglobinuria.

 Extravascular - Erythrocyte destruction occurs outside of the blood vessels through macrophages in the spleen, liver, and bone marrow. Haemoglobinaemia and haemoglobinuria are absent.

 Anaemias caused by decreased erythrocyte production

 Inflammatory disease

 Renal disease

 Marrow hypoplasia or aplasia

 Erythroid hypoplasia or ineffective erythropoiesis

References

1.  Stockham SL, Scott MA, eds. Fundamentals of Veterinary Clinical Pathology. 2nd ed. Ames, IA: Blackwell Publishing; 2008.

2.  Tvedten H. Laboratory and clinical diagnosis of anemia. In: Weiss DJ, Wardrop KJ, eds. Schalm' s Veterinary Hematology. 6th ed. Ames, IA: Wiley-Blackwell; 2010.

3.  Villiers E. Disorders of erythrocytes. In: Villiers E, Blackwood L, eds. BSAVA Manual of Canine and Feline Clinical Pathology. 2nd ed. Gloucester, UK: British Small Animal Veterinary Association; 2005.

4.  Thrall MA. Classification and diagnostic approach to anaemia. In: Thrall MA, Weiser G, Allison RW, Campbell TW, eds. Veterinary Hematology and Clinical Chemistry. 2nd ed. Oxford, UK: Wiley-Blackwell; 2012.