Anaemia

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File:Anaem1.jpg
Feline blood. Regenerative anemia. Immature RBCs are visible as larger erythrocytes that have blue- grey cytoplasm. These cells are termed macro- cytic polychromatophilic erythrocytes. Two NRBCs (arrows) are noted and are smaller than a lymphocyte (100x)

Anaemia in cats is defined as a decrease in red blood cells, haematocrit and haemoglobin. This results in reduced oxygen delivery to all organs and a subsequent decline in cell matabolism[1]. Anaemia is a frequently encountered clinical problem that has many causes ranging from parasites in kittens to chronic renal disease in geriatric cats.

Anaemia is due to either blood loss (haemorrhage), increased blood destruction (haemolysis) or decreased production (erythroid hypoplasia).

  • Regenerative anaemia (>60,000 reticulocytes /ml)
- Hereditary haemolytic anaemia ( pyruvate kinase deficiency, osmotic fragility, porphyria)
- Hypophosphatemia (after treatment of diabetic ketoacidosis, or secondary to hepatic lipidosis)
- Microangiopathic haemolytic anaemia
- Mycoplasma haemofelis / M. haemominutum, Cytauxzoon felis
- Immune-mediated haemolytic anaemia
- Drugs and toxins (acetaminophen, benzodiazepines) result in Heinz-body anaemia
- Blood loss - platelet abnormalities (thrombocytopenia), clotting factor abnormalities, hypertension (retinal haemorrhage, epistaxis)
  • Non-regenerative anaemia
- Chronic renal disease due to reduced erythropoetin production by the kidney
- viral diseases including FeLV, FIV, FIP
- Hypoadrenocorticism
- Hypothyroidism (iatrogenic, 2ry to treatment for hyperthyroidism)
- Iron deficiency, folic acid deficiency
  • Chronic diseases
- Myelophthitic diseases of neoplastic origin
- Ehrlichiosis, Anaplasmosis
- Drugs (e.g. NSAIDs, chloramphenicol)
- Immune-mediated myelophthisis

Anemia is one of the most frequent hematological abnormalities found in cats. Both regenerative and non-regenerative anemia is commonly observed, associated to a myriad of infectious and noninfectious diseases. Non-regenerative anemia is associated to chronic inflammatory processes, neoplasias, endocrinopathies such as diabetes mellitus, renal diseases, and bone marrow diseases. It also occurs as a consequence of feline leukemia virus (FeLV) or feline immunodeficiency virus (FIV) infection. Regenerative anemia usually develops after blood loss or hemolysis. The latter is frequently associated with oxidative damage of red blood cells (RBC), neolasias and primary or secondary immune-mediated syndromes. Many infectious agents as Babesia felis, Cytauxzoon felis and Mycoplasma spp target RBC and infect them, leading to premature destruction of infected cells,either intravascular or extravascularly[2].

In order not to overlook the many causes of anemia, causes of anemia can be grouped broadly into those resulting in decreased red blood cell (RBC) production, those causing blood loss, and those resulting in increased RBC destruction.

Anemia resulting from decreased red blood cell production is always non-regenerative. Blood loss and increased RBC destruction are generally followed by a regenerative response 3-5 days after the initial insult, although chronic gastrointestinal blood loss may become nonregenerative due to iron deficiency. The presence of a regenerative response is suggested by the presence of polychromasia, basophilic stippling, normoblastosis (the presence of nucleated red blood cells), anisocytosis, increased numbers of Howell-Jolly bodies following microscopic evaluation of blood smears. Reticulocytosis is evident following new methylene blue staining of blood smears, or automated counting using flow cytometric methods. Using visual methods, two types of reticulocytes can be identified following the regenerative response to anemia in cats: aggregate and punctate reticulocytes. Aggregate reticulocytes are the most immature form of reticulocytes. The presence of > 1% of these in the peripheral blood indicates active regeneration. Laboratories that report a single reticulocyte count for cats generally are reporting the aggregate reticulocyte count. Punctate reticulocytes are more mature and increased numbers (> 10%) suggest a previous regenerative response, generally within the last 1-2 weeks. Feline aggregate reticulocytosis may not always be very pronounced, even though regeneration is occurring.

Causes

The key feature is low or inadequate erythroid production or release. Unless RBC survival is concurrently shortened (eg, hemorrhage and hemolysis), the onset of anemia and its related signs is insidious. The anemia may be caused by a selective alteration in erythropoiesis (suggested by nonregenerative anemia with normal or normally-responding peripheral blood leukocytes or platelets) or generalized bone marrow injury (suggested by nonregenerative anemia with peripheral blood decreases or abnormal responses by leukocytes or platelets).

Mechanisms for selectively altered erythropoiesis in patients with nonregenerative anemia include deficient hormonal stimulation, deficient or defective nutriture, and disturbed metabolism in or destruction of precursors. Generalized bone marrow injury usually is caused by a toxin, infection, or infiltrative process.These distinctions are not absolute. For instance, a cat with FeLV infection can have nonregenerative anemia alone, pancytopenia, or leukemia/erythroleukemia.

Decreased red blood cell production

This generally reflects impaired bone marrow function. Causes in cats include:

  • Chronic renal disease - this results in a normocytic, normochromic anemia due to decreased secretion of erythropoietin.
  • Myelophthisis - Myelophthisic anemia results from replacement of the marrow by neoplastic cells or fibrosis. Usually deficiencies in other cell lines are present concurrently.
  • Iron deficiency - Iron deficiency anemia is classically microcytic and hypochromic, but occasionally a normocytic, normochromic anemia develops. The combination of low serum iron concentration, low ferritin concentration, and increased total iron binding capacity can be used to diagnose iron deficiency. However, because serum ferritin is an acute phase reactant protein, serum ferritin can increase with inflammatory disease, sometimes impairing the diagnosis of concurrent iron deficiency anemia. In dogs and humans, a lack of bone marrow stainable iron can be used in such situations to aid diagnosis of iron deficiency anemia. Unfortunately, normal cats lack stainable marrow iron. As a result,iron deficiency anemia may be difficult to confirm in some cats. One of the most

common causes of iron deficiency anemia in cats is chronic gastrointestinal blood loss.

  • Anemia of inflammatory disease - this is usually a mild to moderate, normocytic, normochromic anemia. The hematocrit is seldom lower than 14-15%. Anemia of inflammatory disease is suggested by the presence of a decreased to normal serum iron concentration, increased total iron binding capacity, and normal to elevated ferritin concentration.
  • Infectious - The most common infectious cause of decreased red cell production in cats is FeLV infection.
  • Immune-mediated disease - at the level of red blood cell precursors.
  • Toxins - As with myelophthisic disease, toxic causes of anemia operating at the level of the marrow usually cause deficiencies in other cell lines. Examples include chloramphenicol and chemotherapeutic drugs.

Red blood cell loss

Red cell loss may be the result of bleeding from the GI tract, urinary tract, or internal hemorrhage, such as that due to splenic rupture, or hemothorax. Chronic gastrointestinal bleeding may be associated with thrombocytosis and an elevated BUN to creatinine ratio.

Causes of bleeding include:

a) Inherited coagulopathies and platelet disorders
- Haemophilia A (Factor VIII def.) - males, many cat breeds
- Haemophilia B (Factor IX def.) - males, many cat breeds
- Vitamin K-dependent coagulopathy - Devon rex
- Factor XII deficiency - Domestic shorthair, Oriental shorthair cats
- Thrombopathies (rare)
- von Willebrand's disease (rare)
b) Acquired coagulopathies and platelet disorders, including anticoagulant rodenticide toxicity, immune-mediated thrombocytopenia, and hepatopathies
c) Neoplasia, including hemangiosarcoma, intestinal lymphosarcoma, and intestinal adenocarcinoma
d) Severe ulcerative gastroenteritis, such as eosinophilic gastroenteritis
e) Trauma
f) Feline idiopathic lower urinary tract disease
g) Parasitic infections, in particular heavy flea and hookworm infestations

Clinical signs of blood loss include petechiae, ecchymoses, epistaxis, hematemesis, melena, hematomas and hemarthrosis. Internal hemorrhage may be manifest by abdominal distention or tachypnea.

  • Increased RBC destruction

Increased destruction of RBCs may result from:

a) Primary immune-mediated disease: This is less common in cats than in dogs.
b) Immune-mediated disease that is secondary to infection, neoplasia, or drugs: The most common secondary causes of immunemediated hemolytic anemia in cats are infectious.
c) Inherited RBC defects: Osmotic fragility defects and pyruvate kinase deficiency have been particularly recognized in Somali and Abyssinian cats, which may occasionally be misdiagnosed with immune-mediated hemolytic anemia.
d) Hypophosphatemia: Acute hemolysis following hypophosphatemia may occur following refeeding after prolonged anorexia, or with insulin therapy of diabetic ketoacidosis.
e) Toxic causes that result in oxidative damage to red blood cells including Heinz body formation. Feline erythrocytes are more sensitive to such oxidative insults than canine erythrocytes, because of the increased numbers of sulfhydryl groups on feline hemoglobin when compared with canine hemoglobin. Examples of oxidative toxins include acetaminophen, zinc, onions, garlic, and local anesthetics.
f) Microangiopathic damage to erythrocytes: Damage to the endothelium of small vessels results in fibrin deposition and platelet aggregation. As red blood cells travel through the damaged vessels, they are fragmented,

resulting in intravascular hemolysis, sometimes evidenced by the presence of schistocytes on blood smears.

Clinical signs

Clinical signs suggestive of hemolysis include splenomegaly, icterus, hemoglobinemia, and hemoglobinuria. Compared with canine RBCs, feline RBCs are smaller and lack central pallor, so spherocytes are not normally identified in the cat. There are several pathogenic microorganisms that may cause anemia in cats, the most widespread being feline leukemia virus and feline immunodeficiency virus infections, feline hemotropic mycoplasma infections, and feline infectious peritonitis virus infection.

The approach to diagnosis of these infections, and the mechanisms by which they cause anemia are outlined below. Other infectious causes of feline anemia that have a more restricted geographic distribution include the vector-borne protozoan parasites Cytauxzoon felis and Babesia felis. Cytauxzoon felis occurs in south-central and southeastern regions of the United States, and was recently detected in a cat in France. Babesia felis infects cats in coastal regions of South Africa. Other Babesia species have been identified in cats in Europe, India, other parts of Africa, and Israel.

Diagnosis

A diagnosis of anemia may be suspected when a cat presents with lethargy, decreased appetite and pale or white mucous membranes. Findings on physical examination may include tachycardia, tachypnea, or a systolic cardiac murmur as a result of decreased blood viscosity. Definitive diagnosis of anemia depends on the demonstration of a decreased hematocrit, hemoglobin, or total erthrocyte count.

Treatment

Primary treatment requires the establishment of a definable cause and addressing this issue. Supportive therapy such as blood transfusion, blood production stimulants (e.g. erythropoietin) and vitamin supplements are indicated.

References

  1. Chalhoub, S et al (2011) Anaemia of renal disease; What it is, what to do and what's new. JFMS 13:629-640
  2. Hagiwara, K (2009) Anemia in cats: Is it mycoplasma? WSAVA proceedings