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Anemia in Dogs

By Peter H. Holmes, BVMS, PhD, Dr HC, FRCVS, FRSE, OBE, Emeritus Professor and Former Vice-Principal, Faculty of Veterinary Medicine, University of Glasgow ; Nemi C. Jain, MVSc, PhD, Professor Emeritus of Clinical Pathology, Department of Veterinary Pathology, Microbiology, and Immunology, School of Veterinary Medicine. University of California ; David J. Waltisbuhl, BASc, MSc, Senior Scientist DPI&F Actest, Yeerongpilly Veterinary Laboratory ; Michael Bernstein, DVM, DACVIM, Director, Medical Services, Angell Animal Medical Center ; Karen L. Campbell, MS, DVM, DACVIM, DACVD, Professor and Section Head, Specialty Medicine, Department of Veterinary Clinical Medicine, College of Veterinary Medicine, University of Illinois ; Timothy M. Fan, DVM, PhD, DACVIM, Associate Professor, Department of Veterinary Clinical Medicine, University of Illinois ; Wayne K. Jorgensen, BSc, PhD, Science Leader Applied Biotechnology Livestock, Agri-Science Queensland ; Susan L. Payne, PhD, Associate Professor, Department of Veterinary Pathobiology, Texas A&M University

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Anemia occurs when there is a decrease in the number of red blood cells, which can be measured by red blood cell count or hemoglobin concentration. It can develop from loss, destruction, or lack of production of red blood cells. Anemia is classified as regenerative or nonregenerative. In a regenerative anemia, the bone marrow responds appropriately to the decreased number of red blood cells by increasing production of new blood cells. In a nonregenerative anemia, the bone marrow responds inadequately to the increased need for red blood cells. Anemias due to bleeding or the destruction of existing red blood cells are usually regenerative. Anemias that are caused by a decrease in the hormone that stimulates red blood cell production or by an abnormality in the bone marrow are nonregenerative.

Signs and Diagnosis

The signs of anemia in animals depend on the severity, the duration (short or longterm), and the underlying cause of the illness. Sudden anemia can result in shock and even death if more than a third of the blood volume is lost rapidly and not replaced. In severe blood loss, the animal usually has an increased heart rate, pale gums, and low blood pressure. The cause of the blood loss may be obvious, for example, a major injury. If no evidence of external bleeding is found, your veterinarian will look for a source of internal or hidden blood loss, for example, a ruptured tumor on the spleen, a stomach ulcer, or parasites. If red blood cells are being destroyed, the animal may appear jaundiced (a yellowish color of the whites of the eyes, skin, or gums). Animals with longterm anemia have had time to adjust, and their signs are usually slower to develop. These include loss of energy, weakness, and loss of appetite. Affected animals will have similar physical examination findings, such as pale gums, an increased heart rate, and possibly enlargement of the spleen or a heart murmur.

A complete medical history is an important part of diagnosing anemia. Questions a veterinarian may ask include how long signs have been present; if there is a history of exposure to toxins such as rodent poisons, heavy metals, or toxic plants; what drug treatments and vaccinations the pet has had; where the pet has traveled; and any prior illnesses.

A complete blood count is another diagnostic tool your veterinarian will use to provide information on the severity of the anemia, the degree of bone marrow response, and the condition of other types of blood cells. A test should be performed to evaluate red blood cell size and to check for red blood cell parasites (some of which are discussed later in this chapter).

Both blood and urine tests can be used to evaluate how well the internal organs are functioning. If blood loss within the stomach or intestines is suspected, an examination of the animal’s feces under a microscope for trace amounts of blood and parasites can be useful. X-rays can help identify hidden disease, such as a penny in the stomach of a puppy leading to zinc poisoning and anemia. Bruising or bleeding may be signs of a disease or condition affecting the blood’s ability to clot and indicate the need for a test called a coagulation profile. If hemolytic disease (a condition in which there is destruction of red blood cells) is suspected, other tests can be performed. A blood test for infectious agents may also be helpful in defining the cause of anemia.

Bone marrow evaluation is typically done for any animal with an unexplained, nonregenerative anemia. Sampling the bone marrow will require anesthetizing your pet, which may mean it will need to stay at the veterinary hospital overnight.

Blood Loss Anemia

Sudden and severe blood loss can lead to shock and even death if more than 30 to 40% of the total blood volume is lost and the condition is not treated quickly with intravenous fluids or blood transfusions, or both. Causes of severe loss include major injury or surgery. If the reason for blood loss is not obvious, your veterinarian will look for other causes, such as conditions affecting the blood’s ability to clot, bleeding tumors, stomach ulcers, or parasites. Internal parasites, such as hookworms in dogs, can lead to severe blood loss, especially in puppies. Low-grade, longterm blood loss eventually results in iron-deficiency anemia. This leads to abnormally small red blood cells and a lack of hemoglobin. In young animals this is often caused by parasites (for example, fleas, lice, or intestinal worms), but in older animals, bleeding from stomach ulcers or tumors is more common.

Hemolytic Anemia

Hemolytic anemias occur when red blood cells are destroyed. They are usually regenerative. Toxins, red blood cell trauma, infections, immune system defects, and red blood cell membrane defects can all cause hemolytic anemias.

Immune-mediated Hemolytic Anemia

In dogs, the most common cause of hemolytic anemia is immune mediated. This type of anemia can occur on its own or as a result of tumors, infection, drugs, or vaccinations. The body no longer recognizes red blood cells as self and develops antibodies to circulating red blood cells, leading to their destruction.

Dogs with immune-mediated hemolytic anemia are usually jaundiced, sometimes have a fever, and may have an enlarged spleen. They can show mild, slow--developing signs and not appear to be in any pain, or they can suddenly be in severe crisis. Your veterinarian will tailor treatment to the animal’s signs. Any underlying infections will be treated and unnecessary drug therapy discontinued. Fluid therapy may be started and supplemented with blood transfusions if necessary. Drugs are also given to suppress the immune system in order to stop the destruction of red blood cells.

Blocking of a blood vessel in the lungs by a piece that has broken away from a blood clot (known as pulmonary thromboembolism) is a risk for dogs with immune-mediated hemolytic anemia. The underlying cause is unknown, but the risk may be reduced by supportive care with fluids and blood transfusions. Fluids are important to keep kidneys functioning properly and to protect the kidneys from the high concentrations of circulating bilirubin (the reddish yellow pigments in blood that cause jaundice). If the risk for forming blood clots is high, anticoagulant medication may also be given.

Alloimmune Hemolysis

Alloimmune hemolysis is the production of antibodies that are directed against red blood cells of another individual of the same species. Neonatal isoerythrolysis is an example of such a disease and is seen rarely in dogs. It is caused when pups nurse from a mother whose colostrum (the yellowish fluid rich in antibodies and minerals that is produced after giving birth and before producing true milk) contains antibodies to the newborn’s red blood cells. The antibodies develop in the mother during unmatched blood transfusions. Newborns with neonatal isoerythrolysis are normal at birth but develop severe hemolytic anemia within 2 to 3 days and become weak and jaundiced. A veterinarian can perform tests to confirm the diagnosis. Treatment consists of stopping any colostrum while giving supportive care with transfusions. Neonatal isoerythrolysis can be avoided by withholding colostrum from the puppy’s own mother and giving colostrum free of the antibodies. A veterinarian can perform a test to check for alloimmune hemolysis before the newborn is allowed to receive maternal colostrum.

Microangiopathic Hemolysis

Microangiopathic hemolysis occurs when red blood cells are damaged due to turbulent flow through abnormal blood vessels. It can be seen in dogs after having severe heartworm infection, blood vessel tumors (for example, hemangiosarcoma), twisting of the spleen, and disseminated intravascular coagulation, a condition in which small blood clots develop throughout the bloodstream, blocking small blood vessels and depleting the platelets and clotting factors needed to control bleeding. Treatment requires correcting the underlying disease.

Metabolic Causes of Hemolysis

A deficiency of phosphorus in the blood, leading to destruction of red blood cells, is seen in dogs with diabetes, hepatic lipidosis (a disorder of fat metabolism in the liver), and refeeding syndrome (chemical and fluid abnormalities that occur during recovery from fasting or starvation). Providing additional phosphorus, either by mouth or by injection depending on the severity of the illness, is the recommended treatment.

Toxins (Drugs, Plants, Chemicals)

Many classes of drugs can cause anemia if they are ingested accidentally or if their prescribed use is not closely monitored. These include common human and animal drugs such as acetaminophen, aspirin, naproxen, penicillin, and many other antibiotic and antiparasitic agents. Other anemia-causing toxins include plants such as oak, red maple, and bracken fern; foods such as fava beans and onions; chemicals; and heavy metals such as copper, lead, and zinc. It is always important to give as complete a history as possible to the veterinarian when anemia is suspected, in order to help pinpoint the cause.

Infections

Many infections—caused by bacteria, viruses, or other organisms—can lead to anemia, by direct damage to red blood cells (leading to their destruction) or by effects on the elements that produce red blood cells in the bone marrow. In dogs, for example, infections involving certain organisms in the genuses Ehrlichia and Babesia are known to cause anemia.

Inherited Diseases

Several inherited red blood cell disorders cause anemia. Pyruvate kinase (enzyme) deficiencies are seen in Basenjis, Beagles, West Highland White Terriers, Cairn Terriers, and other breeds. Phosphofructokinase (enzyme) deficiency occurs in English Springer Spaniels. Deficiencies in these enzymes lead to shortened red blood cell life span and a regenerative anemia. In dogs with phosphofructokinase deficiency, the sudden destruction of red blood cells is caused by a high blood pH created after excessive excitement or exercise. If such situations are minimized, these dogs may have a normal life expectancy. There is no treatment for pyruvate kinase deficiency, and affected dogs will have a shortened life span due to abnormalities of the bone marrow.

Nonregenerative Anemias

Nonregenerative anemias can be caused by nutritional deficiencies, chronic disease, kidney disease, or bone marrow diseases.

Nutritional Deficiencies

Nutritional deficiency anemias develop when the nutrients needed for red blood cell formation are not present in adequate amounts. Anemia develops gradually and may initially be regenerative, but ultimately becomes nonregenerative. Starvation causes anemia by a combination of vitamin and mineral deficiencies as well as a negative energy and protein balance. The deficiencies most likely to cause anemia are iron, copper, vitamin B12, vitamin B6, riboflavin, niacin, vitamin E, and vitamin C.

Iron deficiency is the most common deficiency seen in dogs. It is rarely nutritional in origin—it most commonly occurs after blood loss (see Anemia in Dogs : Blood Loss Anemia). Young animals do not have much stored iron, and milk contains very little iron. Your veterinarian may recommend oral iron supplements for anemic newborns. Your veterinarian will also look for any hidden source of blood loss and treat it if needed.

B vitamin deficiencies are rare. Some drugs, such as anticonvulsants and drugs that interfere with B vitamin metabolism, may cause anemia. Poor absorption of vitamin B12 has been reported in Giant Schnauzers. These dogs respond to injections of vitamin B12.

Anemia of Chronic Disease

Anemia caused by a longterm (chronic) disease is usually classified as mild to moderate and nonregenerative. It is the most common form of anemia seen in animals. The anemia can occur after a longterm inflammation or infection, a tumor, liver disease, or hormonal disorders such as hyper or hypoadrenocorticism (disorders of the adrenal gland) or hypothyroidism (an underactive thyroid gland). Proteins called cytokines, which are produced by inflammatory cells, lead to decreases in iron availability, red blood cell survival, and the bone marrow’s ability to regenerate, resulting in anemia. Treatment of the underlying disease leads to correction of the anemia.

Kidney Disease

Longterm kidney disease is a common cause of nonregenerative anemia in animals. Animals with kidney disease produce less of a kidney hormone that stimulates development of red blood cells in the bone marrow, leading to anemia. A synthetic form of the hormone has been used for treatment. Animals receiving the treatment require supplemental iron to support red blood cell production.

Bone Marrow Diseases

Bone marrow disease or failure from any cause can lead to nonregenerative anemia and a reduction in the number of all types of blood cells—red, white, and platelets. With widespread marrow involvement, white blood cells are affected first, followed by platelets, and finally red blood cells.

Aplastic anemia (anemia in which the ability of bone marrow to generate all blood cells is reduced) has been reported in dogs. Most cases have no known cause, but some are caused by infections, drug therapy, toxins, or total body irradiation. To treat the condition, the underlying cause must be determined and eliminated. Supportive care such as antibiotics and transfusions may also be needed. Drugs that stimulate the bone marrow can be used until the marrow recovers. If the disease has no known cause or if marrow recovery is unlikely (for example, phenylbutazone poisoning in dogs), bone marrow transplantation is helpful if a suitable donor is available.

In pure red cell aplasia, only the red blood cells or the elements that produce the red blood cells are affected. It is characterized by a nonregenerative anemia with severe reduction of the elements that produce the red blood cells in the bone marrow. It has been reported in dogs. Cases that are immune-related often respond to therapy that suppresses the immune system. A synthetic hormone that stimulates blood cell production has been reported to cause pure red cell aplasia in some dogs. Stopping the hormone treatment may eventually lead to recovery.

Primary leukemias are a type of cancer in which abnormal white blood cells replace normal blood cells. This leads to anemia and a lack of normal white blood cells and platelets. Primary leukemias are uncommon, but they have been reported in dogs. Leukemias can develop in bone marrow or the lymphatic system and are classified as acute (sudden and often severe) or chronic (long-lasting, with signs that are generally less severe). Acute leukemias, in which the marrow is filled with immature blood cells, generally respond poorly to chemotherapy. In animals that do respond, remission times are usually short. In dogs, the response rate to chemotherapy for the most common type of acute leukemia is about 30%, with about half the dogs surviving for at least 4 months. Other types of acute leukemia are less common and even less responsive to treatment. Chronic leukemias, in which there is greatly increased production of one blood cell line, are less likely to cause anemia and are more responsive to treatment.

Myelodysplasia (also called myelodysplastic syndrome) is a bone marrow disorder in which growth and maturation of blood-forming cells in the bone marrow is defective. This leads to nonregenerative anemia or shortages of white blood cells or platelets. It is considered a preleukemic syndrome (occurring before leukemia fully develops). Myelodysplasia occurs in dogs, cats, and humans. The disease can occur as the result of mutations in stem cells or be caused by tumors in other organs or drug therapy. Some dogs respond to treatment with synthetic hormones and steroids. Supportive care with transfusions may be helpful. Survival rates vary because myelodysplasia can progress to leukemia. Many animals with this condition are put to sleep or die of infection, bleeding, or anemia.

Myelofibrosis is a progressive disease leading to anemia and enlargement of the spleen and liver. It brings on bone marrow failure after it causes normal marrow elements to be replaced with fibrous tissue. It can be the initial disease or occur as a result of cancer, immune-mediated hemolytic anemia (see Anemia in Dogs : Immune-mediated Hemolytic Anemia), whole body irradiation, or hereditary anemias. Diagnosis can be made by bone marrow biopsy, a procedure requiring anesthesia and often an overnight stay at the veterinary hospital. Treatment depends on the underlying cause but usually involves suppressing the immune system. Because suppressing the immune system increases the chances that your pet will catch other diseases, carefully follow your veterinarian’s recommendations for controlling exposure to disease-causing agents.

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