In a process called hematopoiesis, all blood cell types are produced through pathways that begin with multipotent stem cells called hemocytoblasts and hemoblasts. Figure 2.1 illustrates the hematopoietic pathways for each blood cell type. Each cell lineage undergoes a series of proliferative phases (mitotic division) and maturation phases, after which they enter a storage pool of mature cells for release into general circulation and, in the case of some leukocytes, distribution to the body. All blood cell types except thrombocytes undergo a series of mitotic divisions followed by several maturation stages during which they shrink in size. Thrombocyte production is unique in that the marrow precursor cells undergo polyploidy without cell division. This results in very large cells with multilobed nuclei that then break up into hundreds of platelets. Hematopoiesis primarily occurs in the bone marrow but it can also occur in the spleen and liver, especially in laboratory mice and rats. The rodent spleen produces mostly erythrocytes but it can also produce granulocytes and megakaryocytes.

Flow cytometry (FCM) is the preferred method for counting RBCs, WBCs, reticulocytes, and platelets. Reticulocyte counts can also be made by counting ≥1,000 erythrocytes in a smear stained with new methylene blue. Hemoglobin is measured by the cyanmethemoglobin method. Wright-stained blood smears are used to microscopically evaluate erythrocyte, leukocyte, and platelet abnormalities, leukocyte counts, differential leukocyte counts, parasites, platelet counts, and bacteria. Wet mounts are preferred for morphology studies since erythrocyte shape is unaltered, and artifacts are minimized. Erythrocyte morphology is further described in the Hematology Diagnosis chapter and the Hematology Glossary. An increase in a cell count has the suffix—philia or—osis (e.g. neutrophilia, monocytosis). A decrease in a cell count has the suffix—penia (e.g. lymphopenia).

Figure 2.1 illustrates the hematopoietic pathways by which various blood cells are produced from multipotent stem cells. Each step of this process is regulated by the cytokines and growth factors adjacent to the yellow arrows. [This illustration was created by proteinlounge.com and is used with their kind permission.]

Approximately one million senescent erythrocytes are replaced every second in the dog. In response to anemia, such as from blood loss or disease, a healthy dog’s bone marrow can produce erythrocytes at 6–8 times the normal rate. The factors needed for erythrocyte production are erythropoietin (EPO, the key cytokine for regulating RBC production), globulins, iron, cobalt, copper, hematopoietic factor, protoporphyrin, vitamins B₂, B₆, and B₁₂, niacin, folic acid, and thiamine. The lack of any of these can lead to anemia, polycythemia, and abnormal erythrocytes.

Anemia is a decrease in the erythrocyte count, hematocrit, and/or hemoglobin. Anemia is not a disease, but rather a sign of disease or trauma. There are four general causes of anemia:

Anemias are either regenerative or non-regenerative (sometimes called responsive or non-responsive anemias). In regenerative anemias, the bone marrow increases erythrocyte production to replace lost or hemolyzed cells, and releases large (macrocytic) immature RBCs such as nucleated erythrocytes and reticulocytes. This response is not seen in non-regenerative anemias.

Table 2.1 shows how anemias can be morphologically classified using two erythrocyte indexes—mean corpuscular volume (MCV) and mean corpuscular hemoglobin concentration (MCHC). Typically, macrocytic anemias are regenerative (responding), normocytic anemias are non-regenerative (non-responding), and microcytic anemias may be either.

The opposite of anemia—erythrocytosis or polycythemia—is an increase in erythrocyte mass in the blood. Both terms are used interchangeably. The most common causes for erythrocytosis in laboratory studies are stress-induced splenic contraction or hemoconcentration (relative erythrocytosis) when an animal is deprived of water. Erythrocytosis may have primary or secondary causes:

A common finding in toxicity studies is hemolysis, the lysing (bursting) of erythrocytes with the release of hemoglobin. Hemolysis occurs naturally in the spleen, liver, and lymph nodes, which each have abundant macrophages. Hemolysis in peripheral blood can be caused by many conditions, diseases, toxicities, pharmaceuticals, and sampling errors, as demonstrated in Table 2.2.