Clinical approach to anemia

The typical clinical signs of anemia are weakness, exercise intolerance, inappetance or anorexia, pale mucous membranes, tachypnea, and icterus. The degree to which these clinical signs are manifested are dependent on the speed at which the anemia develops and the severity of the anemia. A patient with myelofibrosis that develops anemia over the course of many weeks may be surprisingly asymptomatic at a hematocrit of 18%, whereas a dog with acute immune-mediated hemolytic anemia and a hematocrit of 20% may be critical.

Physical examination findings in patients with anemia can be variable depending on the cause, but the clinician should look carefully for any of the following signs: icterus, which is an indication of hemolysis; splenomegaly, which can be seen in immune-mediated disease, hemotropich mycoplasma infection, Babesia, neoplasia (hemangiosarcoma and lymphoma), and extra-medullary hematopoiesis; purpura, which suggests that thrombocytopenia may be present and responsible for the anemia; and heart murmur, which is secondary to decreased blood viscosity with severe anemia.

There are a variety of oddities and miscellaneous points of interest when evaluating the complete blood count and hemogram. For instance: cat platelets are almost the same size as cat red cells and are often times counted as RBCs by most machines—this does not appreciably affect the RBC count, but the platelet counts are usually very low; cat RBCs cannot be detected in machines dedicated for counting human RBCs; Akitas normally have lower MCVs; some poodles may have very high MCVs (poodle macrocytosis); in the presence of anemia, macrocytosis usually reflects current or recent accelerated erythropoiesis; markedly regenerative anemias in dogs are usually accompanied by modest increases in MCV, whereas cats often have MCVs two times normal; prominent macrocytosis may be seen in FeLV-associated anemias whether regenerative or not and has also been seen in nonregenerative anemia in FIP; macrocytosis from Vitamin B12 deficiency (Cobalamin deficiency) is seen in a few breeds (esp. Giant schnauzer and Border collie); microcytosis is a feature of iron deficiency in adult dogs and cats; puppies are born with high MCV and hematocrit—the MCV is normal by 2-3 months, but the hematocrit declines to approximately 30% by 4-6 weeks and gradually increases to normal values by 6-12 months; kittens are born with hematocrit values of ~35% which fall to 25% by 3-4 weeks, and increase to normal by 16 weeks.

Red blood cell morphology can sometimes be indicative of specific disease processes. Some items to keep in mind include: polychromasia indicates increased release of immature cells; nucleated RBCs may accompany reticulocytosis, but are also seen in myeloproliferative disease, dysmelopoiesis, and extramedullary hematopoiesis; basophilic stippling, the spontaneous aggregation of ribosomes and organelles into basophilic granules, should lead to a suspicion of lead toxicity; Heinz bodies, which are hemoglobin precipitated by oxidative injury and are seen frequently in cats and are probably normal in cats in small numbers; spherocytes, red blood cells that are smaller and have lost their central pallor, which are formed when part of the RBC membrane is removed in an immune-mediated process and are the hallmark of immune-mediated hemolytic anemia; and acanthocytes, irregularly shaped RBCs, which are seen in liver disease, hemangiosarcoma, hypercholesterolemia, and feline hepatic lipidosis.

After detemining that a patient is anemic (low hematocrit/PCV/RBC mass), the first question to ask is: Is this regenerative or non-regenerative anemia? Determination of RBC regeneration is made by evaluating the reticulocyte count. The presence of nucleated RBCs and polychromasia are not reliable indicators of regeneration. Remember that with recent blood loss or hemolysis less than 2-4 days old, the regenerative response may be inapparent or inadequate. The easiest and best way to determine if the anemia is regenerative is to calculate the absolute reticulocyte count. This is done by multiplying the percent of reticulocytes by the RBC count. The absolute reticulocyte count should be >60,000 in cats and >100,000 in dogs (some use >60,000 in dogs).

Regenerative anemia is more common and is broadly categorized as hemolytic or hemorrhagic disease. Hemorrhage is characterized by evidence of external blood loss and low total protein, but this may not be true in all cases. With hemolysis, one often sees icterus, hemoglobinuria, bilirubinuria, and normal or increased total protein. When thrombocytopenia is present, remember that it typically requires a platelet count <50,000 in dogs and <10,000 in cats to have spontaneous hemorrhage associated with thrombocytopenia. The most common acquired cause of hemorrhage is a coaguloapthy associated with anticoagulant rodenticides. The identification of iron deficiency anemia should prompt the investigation of GI blood loss, such as from hookwork infestation or bleeding GI neoplasms.

Causes of hemolysis include immune-mediated hemolytic anemia; ehrlichiosis, secondary to vasculitis associated with the infection (a form of microangiopathic hemolytic anemia); Mycoplasma haemofelis, which can produce recurrent, cyclic hemolysis; babesiosis; cytauxzoonosis; oxidative injury which can lead to methemoglobinemia, Heinz body formation, and damage to membrane proteins and is caused by onions and acetaminophen, among other things; pyruvate kinase deficiency, , which is characterized by chronic, severe hemolyis and terminal myelofibrosis by 1-3 years; phosphofructokinase deficiency, which is characterized by mild to moderate chronic hemolysis with superimposed episodes of severe hemolysis precipitated by vigorous exercise or panting associated with overheating; microangiopathic disease, which is seen with hemangiosarcoma, heartworm disease, splenic torsion, disseminated intravascular coagulation, and other neoplasia; zinc toxicity, which is associated with the ingestion of pennies minted after 1983 and other zinc objects; and hypophosphatemia, which can be seen in re-feeding syndromes and during therapy for diabetic ketoacidosis.

Non-regenerative anemia can be caused by extra-marrow disease that inhibits erythropoiesis, either by the inhibition of EPO production, sequestration of iron, or secretion of cytokines that inhibit erythropoiesis. The presence of bicytopenias (non-regenerative anemia with thrombocytopenia or leukopenia) or pancytopenias (all cell lines decreased) supports the presence of intra-marrow disease. Causes of non-regenerative anemia include: anemia of chronic disease, which is the most common form of non-regenerative anemia and is usually mild; chronic renal failure; hypothyroidism and hypoadrenocorticism; FeLV infection; aplastic anemia, which is characterized by severe marrow depopulation and pancytopenias and can be caused by FeLV, estrogen toxicity, phenylbutazone toxicity, trimethoprim-sulfa, chemotherapy, canine ehrlichiosis, or may be idiopathic; myelodysplasia, which is most common in the cat; myeloproliferative disease, which is caused by purposeless, neoplastic proliferation of cells in the marrow; myelofibrosis and osteosclerosis, which are commonly a response to injury to the marrow; lymphoprolierative disorders; and chloramphenicol toxicity, which is less severe in animals than in people and is reversible in dogs and cats.