Chapter 5 Hematologic and Immunologic Diseases
Immune-mediated and hematologic disorders are commonly seen in veterinary practice. Although these diseases may be interrelated in some cases, this chapter discusses the most important diseases as individual entities. The technician is referred to a veterinary hematology text for review of the sequence of erythropoiesis and the function of the immune system; the introduction to this text also should be referenced. Knowledge of hematology and the functions of the immune system will assist the student in understanding these diseases.
Erythrocyte disorders are frequently diagnosed in the dog and cat and may be associated with decreased production, increased destruction, or inappropriate loss of red blood cells (hemorrhage). Included in this category of disorders are anemias, hemorrhage, and neoplasia.
Anemia is one of the most common laboratory findings encountered in veterinary medicine and is usually secondary to a primary disorder elsewhere in the body. The major causes of anemia are varied and include hemorrhage, hemolysis, blood parasites, iron deficiencies, immune-mediated disease, and toxins.
A systematic diagnostic approach to anemia is necessary and should include a good history, physical examination, and a complete blood count, including blood films. Treatment should be aimed at correcting the primary disorder and supporting the patient. Therefore it is important to establish whether the anemia is regenerative or nonregenerative. This can be done by evaluating the reticulocyte count. Regenerative anemias are usually the result of hemorrhage or hemolysis, whereas nonregenerative cases may involve the bone marrow.
Anemia Caused by Hemorrhage
The most common cause of hemorrhage is trauma, although platelet abnormalities and abnormal clotting chemistries must be considered when determining the diagnosis. Acute hemorrhage that occurs as a result of trauma or laceration is usually an easily diagnosable problem. With acute blood loss internally the hematocrit does not reflect the severity of the problem, and as fluid shifts occur to compensate for blood loss, shock may result. Treatment should consist of controlling the hemorrhage and volume replacement.
Thrombocytopenia accounts for many cases of generalized bleeding in pet animals. In these cases, it may be more difficult for the veterinarian to diagnose blood loss. Signs of platelet deficiency include petechial hemorrhages on earflaps, mucous membranes, and on nonhaired areas such as the abdomen. Treatment involves steroid therapy, platelet-rich or whole-blood transfusions, and avoidance of trauma.
Dogs experiencing chronic external blood loss can experience development of iron-deficiency anemia. Severe flea infestation, gastrointestinal parasites, gastric ulceration, and bleeding neoplasms can cause significant blood loss over time. The iron and hemoglobin lost with this external bleeding result in the formation of altered red blood cells with decreased life spans. Treatment consists of correcting the cause of the blood loss and supplementing iron orally for 30 to 60 days.
When immune components attach directly or indirectly to the red blood cell membrane, they alter its structure. The body, in an attempt to regain homeostasis, begins to remove these altered cells. Macrophages interact with the altered cells, resulting in extravascular hemolysis. This disease, when seen in the dog, appears to be related to the presence of an underlying inflammatory process. Affected animals acutely develop exercise intolerance, pale mucous membranes, tachycardia, and icterus if the condition is severe. In cats, the most common cause of hemolytic anemia is haemobartonellosis. Chronic infections with feline leukemia virus (FeLV) may also stimulate immunohemolytic disease in the cat.
Treatment is aimed at suppressing the immune system (steroid therapy) and supportive therapy. Transfusion should be considered if the hematocrit of the cat declines to life-threatening levels. Tetracycline should be used to treat cats with haemobartonellosis.
A special form of immune-mediated hemolytic disease is seen in neonates. This occurs in horses and, rarely, in cats and dogs. The dam passes antibodies against fetal red blood cells in her colostrum. The neonate’s red blood cells are attacked and lysed because they are coated with these antibodies. This problem can be avoided by blood-typing breeding animals and by fostering young born to incompatible dams.
Several commonly seen blood parasitic diseases produce anemia through hemolysis. Mycoplasma hemofelis is a common cause of anemia in cats. The parasite attaches to the erythrocyte membrane, causing increased destruction of the cells. Animals that have nonspecific signs of weight loss, anorexia, fever, hepatomegaly, and splenomegaly should have blood films examined for the presence of this microorganism. Some of these animals may be icteric on examination.
Babesia canis and Babesia gibsoni both produce hemolytic disease in the dog (Fig. 5-1). The brown dog tick Rhipicephalus sanguineus transmits these parasites. The presence of this intracellular parasite results in hemolysis of the infected red blood cells. Diagnosis is accomplished by finding the intracellular organism on blood films or by serology testing. Symptoms exhibited in the dog include hemoglobinuria, dehydration, fever, anorexia, and depression. Treatment involves tetracycline administration (for M. hemofelis) and supportive care.
Figure 5-1 Trophozoites of Babesia canis within canine red blood cells.
(From Hendrix CM, Robinson E: Diagnostic parasitology for veterinary technicians, ed 3, St Louis, 2006, Mosby, by permission.)
Cytauxzoon felis is a protozoal organism from the southern United States (Florida to Texas and Oklahoma) that is responsible for a fatal disease in cats. The intracellular form of the disease produces an anemia, whereas the extracellular form proliferates within the macrophages lining the vascular system, resulting in blood stasis and vascular occlusion. Cats die within days of the development of clinical signs.
Toxin-Induced Anemias/Heinz Body Anemias
Drugs can be the source of anemias in small animals. Exposure of the erythrocyte to oxidants in plasma can result in the formation of reversible and nonreversible hemichromes. When the nonreversible form is present, hemoglobin denaturation continues, forming aggregates of the irreversible hemichromes called Heinz bodies. These aggregates may be seen as large eccentric pale structures within the red blood cell of the cat, or as multiple small structures within the canine red blood cell. Cats are considered to be more susceptible to Heinz body formation because of the structure of their hemoglobin. One of the most common causes of Heinz body anemia in the dog is onion toxicity, primarily from owners treating the dog to table scraps. Clinical signs may appear several days after ingestion and they are usually those of a mild anemia. Acetaminophen toxicity also results in methemoglobinemia and anemia in dogs and cats. Toxic doses are usually the result of the owner medicating the animal. As little as half a tablet can result in clinical signs. Methylene blue, which is a urinary antiseptic used in cats, has long been known to produce Heinz body anemia when given to healthy cats. Specific diseases of clinical significance include immune-mediated hemolytic anemia (IMHA), immune-mediated thrombocytopenia (IMTP), ehrlichiosis, and von Willebrand’s disease (vWD).
Immune-Mediated Hemolytic Anemia
Although the specific cause of IMHA is unknown, the accelerated red blood cell destruction occurs because of the presence of antibodies that attach to the red blood cell membrane. These cells are then removed by the immune system, resulting in anemia. The antibodies may bind directly to the cell membrane or may attach to a microorganism or drug that has previously been bound to the membrane receptor sites. Adherence of these antibodies activates the complement system, causing agglutination and destruction of the red blood cell.
IMHA is found most commonly in dogs 2 to 8 years of age. A breed predisposition exists in poodles, Old English sheepdogs, Irish setters, and cocker spaniels. The disease is four times more prevalent in female than male dogs.
Clinical syndromes seen with IMHA include immune-mediated extravascular hemolysis, intravascular hemolysis, and cryopathic IMHA.
Spherocytes are commonly found on CBC.
As in IMHA, IMTP occurs when platelets become coated with antibodies or complement-antibody complexes. Destruction may occur in the spleen, bone marrow, or liver. The inciting cause is usually unknown, but some drugs such as sulfonamide, chlorothiazide, arsenicals, digitoxin, and quinidine have been associated with the development of IMTP. The disease typically appears in dogs 5 to 6 years of age; female dogs are twice as likely to be affected as male dogs.
As platelet numbers decline to less than 30,000 thrombocytes/mm3 blood, bleeding problems develop. Animals are usually presented for bleeding, most commonly epistaxis. Petechial hemorrhages may appear on mucous membranes, earflaps, and other mucocutaneous surfaces. Bloody stool or blood in vomitus is seen occasionally.
Ehrlichia canis was first recognized in the United States in 1963. The disease gained prominence because of the large losses among military working dogs stationed in Vietnam. The disease is seen primarily in tropical and subtropical environments throughout the world.
This rickettsial disease is spread by the tick vector Rhipicephalus sanguineus, the brown dog tick, and is most commonly diagnosed in dogs living in the southeastern and southwestern United States, which are areas with large tick populations. Infection occurs when the organism is transmitted via the tick saliva during a blood meal. It may also be transmitted by blood transfusion from an infected to a noninfected animal. After infection, the organism multiplies within mononuclear cells, both circulating and fixed (liver, spleen, and lymph nodes). The infected circulating cells can infect other organs. Infection results in vascular endothelial damage, platelet consumption, and erythrocyte destruction. Suppression of the bone marrow also occurs, resulting in aplastic anemia.
Dogs unable to mount an adequate immune response become chronically infected.