The Anaemic Patient
British Small Animal Veterinary Congress 2008
Kate F. Murphy, BVSc(Hons), DSAM, DECVIM-CA, MRCVS
Division of Companion Animals, Department of Clinical Veterinary Science, University of Bristol
Langford, North Somerset

This lecture aims to help the delegate reach a diagnosis in anaemic patients. It is beyond the scope of this lecture to discuss management of the many different causes of anaemia.

Anaemia is a common clinical presentation in small animal practice and should prompt the practitioner to investigate the patient further. A thorough history and full physical examination are the first steps in investigating anaemia. Some important considerations in the history include:

 Age of the patient (e.g., young animals could have congenital disease or have iron-deficiency anaemia secondary to gastrointestinal parasites or ectoparasites; middle-aged animals may be over-represented with immune-mediated disease; older animals may be at greater risk for malignancy-associated anaemia).

 Recent drug therapy or vaccination can be associated with haemolysis, bone marrow suppression or platelet disorders.

 Travel history (travel to areas with endemic red cell parasites or other tick-borne diseases which might cause secondary immune-mediated disease or affect bone marrow production of cells).

 Cats--multicat households, indoor/outdoor--may give indication of relative risk for feline leukaemia virus (FeLV)-or feline immunodeficiency virus (FIV)-associated disease.

 Dietary indiscretion/toxic access (onions, lead).

Typical clinical signs in anaemic patients include lethargy, tachycardia, tachypnoea, pale mucous membranes and bounding peripheral pulses. The severity of clinical signs depends upon the severity of the anaemia and the speed of development of the anaemia. Some patients can present with very low red cell counts, but minimal clinical signs because the anaemia is chronic and they have developed compensatory mechanisms to cope. Patients with immune-mediated disease are frequently pyrexic and animals with haemolytic disease may be icteric. Other clinical signs may give an indication of possible underlying aetiology, e.g., petechiation (Evan's syndrome, marrow failure, disseminated intravascular coagulation, vasculitis), lymphadenopathy (lymphoma, systemic infectious disease, e.g., ehrlichiosis). A systolic 'flow' murmur may be heard due to alteration in blood viscosity.

Anaemia is a physiological abnormality and not a diagnosis. The practitioner should always aim to make a final diagnosis and the first step involves assessing haematology (packed cell volume (PCV)/ automated haematology analyser and smear evaluation). Anaemia can be classified as regenerative (blood loss or haemolysis) or non-regenerative (reduced red cell production due to chronic disease or bone marrow failure, or pre-regenerative anaemia) (Figure 1).

Figure 1. The typical analytical features of the common types of anaemia.

 

Macrocytic anaemia

Microcytic anaemia

Normocytic anaemia

Haematocrit/haemoglobin/PCV/ RBC count

Decreased

Decreased

Decreased

Mean cell volume

Increased

Decreased

Normal

Mean cell haemoglobin concentration

Decreased (hypochromic)

Decreased (hypochromic)

Normal (normochromic)

Reticulocyte count
(It is important to remember that in cats both aggregate and punctate reticulocytes will be seen, but the most reliable indicator of regeneration is an absolute aggregate count)

Increased

Increased initially and then chronically normal

Normal

Typical features on smear evaluation

Anisocytosis and polychromasia suggesting regeneration.
Spherocytes: immune-mediated.
Heinz bodies: oxidative damage

Microcytosis, other abnormal shaped erythrocytes.
Polychromasia often present but less than expected for degree of anaemia

Normocytic and normochromic.
May have abnormal shaped erythrocytes

Possible aetiology

Haemorrhage
Haemolysis (immune-mediated/non-immune-mediated)

Iron-deficiency anaemia (chronic external blood loss)

Chronic disease (inflammatory, endocrine, renal)
Bone marrow disease
Pre-regenerative: acute blood loss or haemolysis

In addition to considering the red cell line, appropriate attention to the other cell lines (platelets and white cells) must be given. In patients with haemolytic disease it is not uncommon to see moderate to marked leucocytosis as part of the bone marrow response. In primary bone marrow disease there may be other cell lines affected (pancytopenia) in addition to the reduction in the red blood cells. If the only cell line affected in bone marrow disease is the red cells, it is important to look for evidence of immune-mediated attack against the red cell precursors to assist in the management of the patient.

Further diagnostics include:

 Serum biochemistry--assess for underlying disease. In acute haemorrhage, serum proteins may be decreased. In haemolytic anaemia there is often elevation of bilirubin and liver enzymes.

 Infectious disease screening--the diseases which are investigated will reflect geographical location of the patient and travel history and also be influenced by the clinical signs and type of anaemia. In cats, assessing viral status (FeLV and FIV) is important, as is screening for mycoplasma infections; polymerase chain reaction (PCR) is available for the three known species of mycoplasma: Mycoplasma haemofelis, Candidatus Mycoplasma haemominutum, Candidatus Mycoplasma turicensis. In travelled patients assessment for red cell parasites is important. Babesia is best diagnosed either by identifying the parasite on blood smear evaluation (preferably of capillary blood) and/or with positive PCR result. Other parasites should also be considered.

 Urine is important in identifying a potential source of external blood loss, identifying haemoglobinuria/bilirubinuria in patients with haemolysis and confirming inadequate urine-concentrating ability in patients with anaemia caused by chronic renal failure.

 Faecal analysis for evidence of gross blood loss (melaena or haematochezia) or occult blood loss (must be fed meat-free diet for at least 3 days) is useful. Faecal parasitology is indicated in patients with confirmed intestinal blood loss (along with other investigations of gastrointestinal disease).

 Diagnostic imaging of the thorax and abdomen is often used to screen for underlying disease, e.g., neoplasia. Usually a combination of radiography and ultrasonography provides the most useful information. If abnormal organs/ masses are identified, fine-needle aspiration can be a helpful adjunctive test.

 A coagulation profile might be performed if a primary coagulopathy is considered or if secondary disseminated intravascular coagulation is suspected.

 A bone marrow aspirate and core biopsy may be performed in non-regenerative or poorly regenerative anaemia. In cats consider PCR analysis of bone marrow for viral disease.

 Erythropoietin may be measured in patients with anaemia secondary to chronic renal failure.

 Oestrogen toxicity is a reported cause of non-regenerative anaemia. In male dogs with testicular neoplasia and anaemia consider submitting blood to measure oestrogen levels. Oestrogen is sometimes used therapeutically (e.g., misalliance, urinary incontinence) and should be considered potentially toxic.

 Genetic tests are available for certain hereditary erythrocyte defects.

 Iron stores can be assessed by measuring serum iron, serum ferritin, total iron-binding capacity (TIBC), percentage transferrin saturation and ultimately by bone marrow haemosiderin stores (Figure 2). This can be useful to help differentiate mild/moderate microcytic hypochromic or normochromic anaemia, which could be caused by iron deficiency, from anaemia of chronic inflammatory disease. Severe microcytic hypochromic anaemia is almost certainly due to iron deficiency.

 Anaemia can occur secondary to nutritional deficiencies, e.g., folate or cobalamin, which can result in macrocytic normochromic anaemia. Therefore measurement of vitamin B12 and folate is indicated in patients with this type of anaemia.

 If anaemia is suspected to be secondary to endocrine disease, the tests appropriate for the diagnosis of that disease should be performed, e.g., adrenocorticotrophic hormone (ACTH) stimulation test for hypoadrenocorticism, T4/thyroid-stimulating hormone (TSH) for hypothyroidism.

 Blood typing/cross-matching should be considered in any patient likely to require blood transfusion.

 If haemolytic anaemia is suspected a slide agglutination test and/or Coomb's test can be performed to provide evidence for an immune-mediated (primary or secondary) aetiology; it must always be remembered than an underlying disease may have resulted in immune-mediated haemolysis.

Blood loss anaemia often presents the practitioner with a diagnostic challenge to identify the source of blood loss. Some further guidelines on this type of anaemia are given; if the patient has blood loss anaemia the history and laboratory data should help the practitioner to differentiate between acute and chronic blood loss. Acute haemorrhage can occur because of trauma, during or after surgery, rupture of vascular tumour, bleeding gastrointestinal ulcers/tumours or with bleeding disorders/coagulopathy (e.g., rodenticide intoxication), Angiostrongylus vasorum infection. Chronic external blood loss typically results in iron-deficiency anaemia (young animals become iron deficient more quickly because they have low iron stores and their bone marrow is less able to increase the rate of haematopoiesis). Chronic external blood loss can result from blood loss into the gastrointestinal tract (ulceration, parasitism, neoplasia, inflammatory bowel disease (IBD)), into the urogenital (neoplasia, chronic infectious/inflammatory, idiopathic renal haemorrhage) or respiratory (nasal or pulmonary, frequently due to neoplasia) tracts or from the skin surface (ectoparasites). Blood loss can occur due to abnormalities of the haemostatic mechanisms, e.g., thrombocytopenia, thrombocytopathia, vasculitis, coagulopathies (as discussed above, many potential causes).

Figure 2. A simplistic approach to iron profiles.

 

Iron-deficiency anaemia

Anaemia of chronic inflammatory disease

PCV

Can be mildly or severely decreased

Mild to moderate anaemia only

Serum iron

Low

Low

Total iron-binding capacity

Normal or high

Low

% Transferrin saturation

Low

High

Bone marrow iron stores

Low

High

Speaker Information
(click the speaker's name to view other papers and abstracts submitted by this speaker)

Kate F. Murphy, BVSc(Hons), DSAM, DECVIM-CA, MRCVS
Division of Companion Animals, Department of Clinical Veterinary Science
University of Bristol
Langford, North Somerset, UK


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