Reticulocytes are immature anuclear erythrocytes. They contain RNA and mitochondria which aggregate into a reticular pattern, hence the name reticulocyte. Reticulocytes typically reside in the bone marrow for 2 days before release into the circulation where they become mature erythrocytes after about a day. When there is accelerated erythropoiesis, reticulocytes are released from the bone marrow early and thus remain in the immature form for longer in the circulation. The number of reticulocytes in circulation is used as an index of bone marrow activity in response to anemia. After induction of anemia, it takes 48-72 hours before reticulocytosis will be evident, with a maximum response at about 7 days.
There are several ways to enumerate reticulocytes, one of the most common of which is the absolute reticulocyte count. An absolute recticulocyte count can be overestimated by automated hemotology analyzers in patients with Heinz bodies, Howell-Jolly bodies or punctate reticulocytes. Therefore, reticulocyte counts from automated systems should always be confirmed with a manual count. An absolute reticulocyte count of greater than 80,000/ul in dogs or 60,000/ul in cats indicates a regenerative response.
Hemolysis and blood loss are the two general pathologic mechanisms that can lead to a regenerative anemia. Blood loss can be either external (e.g. external trauma, GI, urinary or respiratory tract) or internal (e.g. hemothorax, hemoperitoneum, hemopericardium, fracture site hemorrhage) in nature. There are many causes of blood loss including coagulopathy, trauma, neoplasia, parasitism, inflammatory lesions and ulceration. There is an extensive list of disease processes that can lead to hemolytic anemia including hemoglobin disorders, cell membrane fragility, erythroenzymopathies, immune-mediated hemolytic anemia, alloimmune hemolytic anemia, infection-induced hemolysis, oxidative damage and microangiopathic hemolytic anemia.
When reticulocytosis is noted with a normal hematocrit, care should be taken to insure that hemoconcentration is not masking the presence of anemia. In a situation where the patient appears clinically normal, yet a reticulocytosis is note on a routine laboratory evaluation (i.e. wellness exam), a complete evaluation of the patient’s history, physical examination, CBC, serum biochemical analysis and UA should be performed with a particular focus on identifying evidence of or risk factors for hemolysis or blood loss. A blood smear should be evaluated and a manual reticulocyte count performed to confirm the presence of a regenerative response. If no evidence of blood loss or hemolysis is noted and the patient appears to be otherwise healthy, the patient should be carefully monitored and the reticulocyte count and CBC repeated in 5-7 days. Persistent reticulocytosis should alert the clinician to possible low grade or clinically inapparent blood loss or hemolysis and appropriate diagnostic steps should be taken to identify the source of the problem.