Non-Regenerative Anemia in Dogs

Anemia is a decrease in the mass of red blood cells, the result of lack of production, loss of red blood cells, or destruction of red blood cells. There are two types of anemia: regenerative and non-regenerative. With regenerative anemia, alternatively, the bone marrow responds to the anemia by increasing production of red blood cells and releasing reticulocytes (immature red blood cells that don’t have a nucleus). Regenerative anemia can be caused by a hemorrhage or hemolysis (the rupture or destruction of blood cells). In non-regenerative anemia, the cause is usually a decrease in erythropoietin (a hormone controlled by the kidneys that influences red blood cell production as a response to low oxygen in tissues) or bone marrow abnormalities. The bone marrow does not effectively respond to the decrease levels of red blood cells. 

Non-regenerative anemia is a deficiency of the red blood cells where the bone marrow is not appropriately addressing the deficiency by increasing red blood cell production and releasing reticulocytes. Symptoms include lethargy, jaundice, fever, pale mucous membranes, and abnormal pulses.

Symptoms vary depending on the degree, duration, and cause of the anemia, but may include:

• Tachycardia (fast heart rate)
• Pale mucous membranes
• Abnormal peripheral pulses
• Hypotension (low blood pressure)
• Lethargy
• Weakness
• Anorexia
• Splenomegaly (enlarged spleen)
• Abdominal distension
• Heart murmur
• Jaundice
• Fever
• Shock
• Death

Types

Non-regenerative: Non-regenerative anemia is determined by the absence of reticulocytosis, indicating that erythropoiesis (red cell production) is not functioning properly. Non-regenerative anemia develops slowly and has many potential causes. 

Regenerative: Regenerative anemia is characterized by reticulocytosis, a condition where reticulocytes (immature red blood cells) are increased in circulation. This indicates that the body is responding appropriately to the anemia by releasing red blood cells (before they have matured) to compensate for the lower levels in the blood stream. These reticulocytes are polychromatophilic (they have an affinity to multiple acid, neutral and/or basic stains) on routine blood tests.

• Anemia of chronic disease/anemia of inflammation: This is the most common cause of non-regenerative anemia, typically shares similarities with iron deficiencies
• Absolute iron deficiency: This cause of iron deficiency in dogs is typically caused by chronic blood loss such as in gastrointestinal disease, hookworms, neoplasia, and ulcerations (can cause hemorrhages which lead to iron deficiency)
• Chronic renal failure: In cases of chronic renal failure, a decrease in erythropoietin may cause non-regenerative anemia
• Neoplasia: Non-regenerative anemia can be a complication of cancer, though this is not the case for all cancers; anemia related to cancers is the result of bleeding or hemolysis caused by the neoplasia
• Endocrinopathies: Endocrine diseases such as hypothyroidism, diabetes mellitus, and hypoadrenocorticism, can be associated with non-regenerative anemia
• Liver disease: Non-regenerative anemia caused by liver disease occurs most regularly in cases of chronic liver disease
• Infection of erythropoietic cells: Some viruses can cause infection in the erythropoietic cells, causing non-regenerative anemia
• Disease or toxic injury to bone marrow: Any affliction to bone marrow can cause non-regenerative anemia because it inhibits the bone marrow’s ability to produce red blood cells

Your veterinarian will likely ask questions to establish a complete medical history. Some of these questions may focus on symptoms, exposure to certain toxins (such as rodenticides, heavy metals, or toxic plants), current drug treatments, vaccinations, history of travel, or previous illnesses. In addition, the following diagnostic tests may be used:

• Physical exam
• Complete blood count, particularly with focus on abnormalities and possible red blood cell parasites 
• Urinalysis
• Bone marrow evaluation

Analysis of red blood cells will focus on size and hemoglobin concentration. Complete analysis of the red blood cells will help to identify or rule out potential causes, including macrocytosis (increase in mean corpuscular volume) which suggests regenerative anemia, microcytosis (decrease in mean corpuscular volume) which indicates anemia from iron deficiency, lead poisoning established through abnormalities in hemoglobin concentration, and oxidative injury indicated by Heinz body formation.

Treatment depends on the underlying cause and severity of the regenerative anemia, as well as any underlying conditions that are causing or influencing the anemia, which may include cancer, liver disease, and renal failure. Treatment could include fluid therapy and, in many cases, blood transfusions. Treatment of the cause will need to be considered, and may need to be addressed before the anemia. Recovery will likely include periodic blood transfusions, though that depends on the cause of the non-regenerative anemia. Prognosis varies, ranging from good to poor.

• Fluid therapy
• Blood transfusions, in severe cases
• Removal of any drugs or irritants that could be causing the anemia, especially in instances where the drug is toxic to the bone marrow
• Most genetic diseases have no real treatment
• Treatment of the underlying causes of the anemia, including liver disease, chronic renal failure, and endocrine diseases

Recovery and management will depend largely on the underlying condition. If the anemia cannot be completely treated, your veterinarian will likely require multiple follow up visits for blood transfusions or supplemental therapy to help with the anemia. Depending on the cause, treatment, as well as post-treatment recovery, will vary—cause and follow up treatment will influence prognosis.