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ANEMIA – GENERAL DIAGNOSTIC APPROACH

ANEMIA – GENERAL DIAGNOSTIC APPROACH

ANEMIA is a decrease in the red blood cell mass that results in decreased oxygenation of tissues. On complete blood count (CBC), it can be diagnosed by red blood cell (RBC) count, hematocrit (HCT) or hemoglobin (Hb) below the reference values. Remember, in some situations, normal values of individual animal can be above (sight hounds) or below (pregnancy, puppy) the reference range for the species.

Clinical signs of anemia are consequence of decreased oxygenation or compensatory mechanisms. The main manifestation are pale or icteric mucous membranes, lethargy, exercise intolerance and decreased activity. Additionally, tachypnea or dyspnea, tachycardia, heart murmur, petechiae, blood in the stool, hematuria (evidences of bleeding), pigmented urine, lymphadenopathy, spleno- and hepatomegaly can be noticed. Signs can be acute or chronic – acute blood loss results in acute presentation, but chronic blood loss or marrow dysfunction usually have chronic onset of clinical signs. Compensatory mechanisms can keep animals with chronic anemia asymptomatic for a longer period, until HCT drops too low, compensation fails and animals develop acute signs.

The degree of anemia and severity of clinical signs may be helpful in establishing its cause: bleeding, iron deficiency and anemia of chronic or renal disease usually don’t cause a severe decrease in HCT. Animal with severe anemia (HCT below 18% in dogs and 14% in cats) and mild clinical signs more likely has chronic bone marrow disorder, but severe anemia with severe clinical signs suggests, that the course of disease is too acute for adaptive compensatory mechanisms to occur, which happens in case of acute hemolysis.

Important and simple additional tests for diagnosing mechanism of anemia are reticulocyte count, examining plasma for evidence of icterus or hemolysis, measuring protein content in plasma (blood loss usually results in hypoproteinemia, hemolysis does not), performing slide agglutination test and examining blood smear (evaluating RBC size and morphology, numbers and morphology of WBCs and platelets, the presence of autoagglutination, nucleated RBCs, polychromasia, RBC parasites).

Anemia is not a primary diagnosis – attempt should always be made to identify its mechanism and underlying disorder, because appropriate therapy and prognosis depend on it.

Important information, one should obtain from the owner of anemic cat or dog:

  • current medication: some drugs can cause hemolysis, bone marrow hypoplasia or gastrointestinal bleeding;
  • signs of blood loss or dark stool: gastrointestinal bleeding from ulcer or tumor;
  • noticing any fleas or ticks and protection against them: severe flea infestation can cause iron deficiency anemia, ehrlichiosis – marrow hypoplasia, babesiosis – hemolysis;
  • FeLV, FIV status: infection with retroviruses can cause bone marrow hypoplasia, myelodysplasia or leukemia;
  • recent vaccinations: modified live vaccines can cause platelet dysfunction, thrombocytopenia and immune-mediated hemolysis;
  • disruption of pregnancy: estrogen derivates can cause bone marrow aplasia or hypoplasia;
  • detailed travel history: certain infectious diseases that cause anemia, may have geographic distribution.

For clinical purposes, anemia can be classified by erythrocyte size and hemoglobin concentration or bone marrow response.

Classification of anemia based on erythrocyte size and hemoglobin concentration

By measuring erythrocyte volume (MCV) we can describe anemia as microcytic when erythrocytes are small, normocytic when they are normal size or macrocytic when they are larger than normal reference. Amount of hemoglobin within erythrocytes (MCHC) determines anemia as hypochromic when erythrocytes contain less than normal hemoglobin or normochromic, when hemoglobin concentration is normal. Hyperchromic anemia doesn’t occur – MCHC can be falsely increased in case of hemolysis, lipemia or presence of Heinz bodies.

  • Microcytic anemia: most common with iron deficiency; microcytosis also possible with portosystemic shunt, normal in Akita, Shiba Inu
  • Normocytic anemia: usually non- or preregenerative (may also be regenerative)
  • Macrocytic anemia with polychromasia: functional bone marrow response – regeneration
  • Macrocytic anemia without polychromasia: FeLV, myelodysplasia, poodle macrocytosis
  • Hypochromic anemia: increased concentration of immature cells (regeneration), occasionally iron deficiency

Classification of anemia based on bone marrow response

Based on number of circulating immature erythrocytes, anemia can be defined as regenerative or nonregenerative. Those values are obtained by measuring reticulocyte count or evaluating blood smear for the presence of polychromasia. Reticulocyte count should always be interpreted in connection with HCT (number of reticulocytes should be higher with lower HCT).

  • In regenerative anemias increased numbers of immature erythrocytes are released into the circulation, indicating functional bone marrow. The causes are hemolysis (immune-mediated, blood parasites, chemicals that produce oxidative damage resulting in Heinz body formation, hereditary membrane defects or enzyme deficiencies leading to metabolic disorders, hypophosphatemia) or blood loss (trauma, bleeding lesions, hemostatic disorders, parasites). An increased concentration of reticulocytes is usually seen within 2–4 days after erythrocyte loss. Acute onset of regenerative anemia requires aggressive therapy.
  • Nonregenerative anemias are diagnosed by lack of circulating reticulocytes in the face of anemia and are evidence of bone marrow dysfunction. They are caused by bone marrow disorders (aplastic anemia, pure red cell aplasia, myelodysplastic syndromes, myelophthysis, myelofibrosis) or can be secondary to disorders, extrinsic to bone marrow (chronic disease, renal disease, endocrine disorders, nutritional deficiencies). Most nonregenerative anemias are chronic, which allows physiologic adaptation to the decreased erythrocyte mass. Therefore, they may be incidental finding during routine evaluation of asymptomatic animal. Acute hemolysis and blood loss are also nonregenerative in the first 2–4 days, before bone marrow reacts with regenerative response.
  • Iron deficiency anemia is usually classified as nonregenerative, but it can show mild regeneration, depending upon the magnitude of iron loss (greater iron deficiency limits regeneration). RBC indices are different as in other nonregenerative anemias.

LITERATURE:

Thrall M. A., Weiser G., Allison R. W., Campbell T. W.: Veterinary Hematology and Clinical Chemistry. 2nd Ed. Wiley-Blackwell, 2012

Nelson R. W., Couto C. G.: Small Animal Internal Medicine, 4th Ed. Mosby Elsevier, 2009