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. 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. 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). Treatment depends on the underlying cause, but may include fluid therapy, removal of any external causes (such as drugs or foods), and blood transfusions. Prognosis depends on the cause, but in many cases, continued transfusions may be required.

Regenerative anemia is a type of anemia where the bone marrow acts as it is supposed to by releasing reticulocytes (immature red blood cells) in an attempt to make up for the absence of red blood cells. This loss of red blood cell mass can be caused by blood loss, poisoning, decreased bone marrow production, or genetics, among other causes. Symptoms include tachycardia, hypotension, lethargy, and weakness. 

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

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.

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 anemia can be caused by poisoning, infection, trauma, or other conditions that may cause a loss of blood or hemolysis (shortened life span of erythrocytes). Some of these possible causes include:

• Oxidation
• Blood loss
• Immune-mediated hemolysis: This is the most common cause of regenerative anemia in dogs, where the body identifies red blood cells as foreign and therefore, begins to destroy them
• Hemolysis
• Decreased marrow production
• Ehrlichia spp infection
• Babesia spp infection
• Alloimmune hemolysis: The production of antibodies directed against red blood cells of another in the same species, this is seen in newborns where the mother’s colostrum (yellowish fluid produced after giving birth and before milk production) contains antibodies to the red blood cells of the newborn
• Microangiopathic hemolysis: Damage occurs to red blood cells from speeding through abnormal blood vessels; can be found in dogs following heartworm infection, blood vessel tumors, twisting of the spleen, or blocking small blood vessels and depleting platelets
• Hemolysis caused by phosphorous deficiency, seen in dogs with diabetes, hepatic lipidosis, and refeeding syndrome
• Genetic causes: Pyruvate kinase (enzyme) deficiencies occur in Basenjis, Beagles, West Highland White Terriers, and Cairn Terriers. Phosphofructokinase (enzyme) deficiencies occur in English Spring Spaniels

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. Some of these treatments may include:

• Fluid therapy
• Blood transfusions, in severe cases
• In newborns with alloimmune hemolysis, stopping colostrum intake
• Supplementation of phosphorous, particularly in metabolic cases
• Removal of any drugs or irritants that could be causing the anemia (such as acetaminophen, aspirin, naproxen, penicillin, oak, red maple, and bracken fern, fava beans and onions, or heavy metals)
• Most genetic diseases have no real treatment

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.