Douglas J. Weiss,     St. Paul, Minnesota

Evaluation of Nonregenerative Anemias

Nonregenerative anemias are caused by a variety of primary and secondary disease processes that must be differentiated before determining a prognosis or instituting a therapeutic plan. A diagnostic plan for evaluation of anemic disorders is outlined in Web Box 30-1. Initial evaluation of the animal should include a careful history to exclude drug or toxin exposure that may have caused the hematologic dyscrasia. Initial evaluation of the anemia should include a complete blood count, blood smear examination, and reticulocyte count. In addition, immune-mediated and infectious causes of anemia should be evaluated with appropriate diagnostic testing. Mild-to-moderate nonregenerative anemias (packed cell volume [PCV] 20% to 37% in dogs and 14% to 26% in cats) frequently occur secondary to inflammatory neoplastic, renal, hepatic, and certain endocrine disorders. Appropriate testing should be performed to detect these conditions. If a definitive diagnosis is not achieved based on the initial evaluation, bone marrow aspiration cytology and core biopsy are indicated. The combination of bone marrow aspiration cytology and core biopsy is essential to evaluate fully cytologic details and histopathologic alterations. Bone marrow evaluation may result in a clinical diagnosis (e.g., acute myelogenous leukemia, myelodysplastic syndrome). In these situations, treatment usually can be pursued without further diagnostic evaluation. Other bone marrow reports may provide only a pathologic diagnosis (e.g., aplastic anemia, myelofibrosis, myelonecrosis). Each of these pathologic diagnoses have multiple causes, and additional testing is needed to define the underlying cause and establish an approach to treatment and a prognosis. For example, myelofibrosis can be caused by immune-mediated hemolytic anemia, systemic bacterial infections, endotoxemia, drug-induced bone marrow toxicity, and malignant neoplasia.

Drug-Induced Hematologic Dyscrasias

A growing number of drugs are associated with hematologic disorders in animals. Some drugs, most notably chemotherapeutic agents and oxidant compounds, cause dose-dependent hematologic disorders (type A adverse drug reactions) frequently at or near the therapeutic doses. Other drugs induce idiosyncratic hematologic dyscrasias (type B adverse drug reactions). The most frequent types of idiosyncratic hematologic drug reactions are immune-mediated hematologic reactions and toxic injury to bone marrow. Drugs most frequently reported to induce hematologic dyscrasias include chemotherapeutic agents (dog, cat), estrogenic compounds (dogs), phenylbutazone (dog), acetaminophen (dog, cat), trimethoprim/sulfadiazine (dog), phenobarbital (dogs), azathioprine (dog, cat), propylthiouracil (cats), methimazole (cats), and griseofulvin (cat). Other drugs associated with hematologic dyscrasias include phenacetin (dog), benzocaine (dog, cat), propofol (cat), methylene blue (dog, cat), diphenylhydrazine (dog) DL-methionine (cat), phenazopyridine (cat), cephalosporins (dog), carprofen (dog), chloramphenicol (dog), primidone (dog), naproxen (dog), phenytoin (dog), metronidazole (dog), levamisole (dog), albendazole (dog, cat), fenbendazole (dog), thiacetarsamide (dog), amiodarone (dog), captopril (dog), quinidine (dog), colchicine (dog), and mitotane (dog).

Hematologic Disorders Secondary to Other Disease Processes

Inflammatory diseases are accompanied consistently by a mild-to-moderate normocytic, normochromic, nonregenerative anemia, a condition termed anemia of inflammatory disease (AID). The hematocrit drops within the first few days to weeks after onset of inflammation and then stabilizes. Anemia also frequently accompanies large or metastatic malignancies. Multiple causes of anemia may be involved, including AID and acute or chronic blood loss. Chronic blood loss can cause iron deficiency that further impairs erythropoiesis. Microangiopathic hemolytic anemia can result from damage to vascular endothelium or from fibrin deposition within the vessels. The hallmark of this process is the presence of schistocytes and keratocytes in the blood of affected animals. In most animals with AID the anemia is mild and does not require treatment. The anemia usually resolves with successful treatment of the underlying disease. The anemia is, however, responsive to erythropoietin (EPO) therapy.

Chronic renal disease/renal failure consistently results in normocytic, normochromic, nonregenerative anemia. The anemia, although complex, is primarily the result of decreased EPO production by the kidney. Although the anemia is initially mild to moderate in severity, it can become severe in the late stages of the disease. AID associated with canine and feline chronic renal failure is responsive to EPO replacement therapy. A side effect of administration of recombinant human EPO is bone marrow erythroid hypoplasia or pure red cell aplasia due to development of antibodies against the recombinant EPO that neutralizes the animals’ own EPO. Species-specific recombinant EPO should be used if it is available.

Infectious Diseases