PATHOLOGY - Small Animal Anaemia Flashcards
What is anaemia?
Anaemia is the reduction in haemaglobin concentration in the blood
What is erythropoiesis?
Erythropoiesis is the process by which erthythropoietic stem cells develop into mature erythrocytes
Describe the physiological regulation of erythropoiesis
Decreased oxygen delivery to the kidneys stimulates the production and secretion of the erythropoietin (EPO) into the bloodstream to stimulate erythropoiesis
Which three components are required for haemaglobin production?
Iron
Vitamin B12 and folate
Functional bone marrow
What are the clinical signs of acute anaemia?
Tachycardia
Tachypnoea
Hyperpnoea
Pale mucous membranes
Bounding or weak pulses
Hypotension
What are the clinical signs of chronic anaemia?
Lethargy
Weakness
Exercise intolerance
Anorexia
Pale mucous membranes
What are the three main classifications of anaemia?
Non-regenerative anaemia
Regenerative anaemia
Pre-regenerative anaemia
What is pre-regenerative anaemia?
Pre-regenerative anaemia is when reticulocytes and other indicators of regeneration are not seen in the blood, but there has not been sufficient time for them to appear
What is non-regenerative anaemia?
Non-regenerative anaemia is where the bone marrow does not have an adequate response to decreased erythrocytes
What are the two main causes of non-regenative anaemia?
Primary bone marrow disease
Secondary failure of erythropoiesis
What are the distinguising clinical signs of anaemia caused by primary bone marrow disease?
Lethargy
Weakness
Exercise intolerance
Relatively bright alert responsive for degree of anaemia
Other cell lines may be affected (e.g. thrombocytopenia)
Clinical signs relate to a gradual reduction in O2 carrying capacity
List seven examples of primary bone marrow diseases
Aplastic anaemia
Red cell aplasia
Pancytopenia
Myelofibrosis
Bone marrow infiltration
Myelodysplastic syndrome
Precursor immune-mediated haemolytic anaemia
What is aplastic anaemia?
Aplastic anaemia is the immune mediated destruction of hematopoietic stem cells
What is red cell aplasia?
Red cell aplasia is the immune mediated destruction of erythrocyte progenitor cells
What is pancytopenia?
Pancytopenia is when there is a deficiency in all three celllular components of blood (erythrocytes, leukocytes, thrombocytes)
Caused by aplastic anaemia
Which neoplasia can cause pancytopenia?
Sertoli cell tumour in male intact dogs
What is myelofibrosis?
Myelofibrosis is a neoplastic disease where bone marrow is infiltrated and replaced with fibrotic tissue
What is myelodysplastic syndrome?
Myelodysplastic syndrome is a neoplastic condition in which hematopoietic stem cells do not correctly develop into mature blood cells
Which species is myelodysplastic syndrome more commonly seen in?
Cats as myelodysplastic syndrome can be caused by feline leukaemia virus (FeLV)
What is precursor immune-mediated haemolytic anaemia?
Precursor immune-mediated haemolytic anaemia is immune-mediated destruction of erythrocyte precursors within the bone marrow
List five examples of causes of secondary failure of erythropoiesis
Anaemia of inflammatory disease
Chronic renal disease
Endocrine disease
Haemaglobin synthesis defects (e.g. iron deficiency)
Nuclear maturation defects (e.g. cobalamin also known as vitamin B12 deficiency)
How does inflammatory disease cause secondary failure of erythropoiesis?
Inflammation triggers cytokine release and cytokines can prevent the release of intracellular iron which will prevent haemoglobin production
This is to prevent bacteria deriving energy from oxidising iron
How does chronic kidney disease cause secondary failure of erythropoiesis?
Chronic kidney disease will impair erythropoietin secretion into the bloodstream to trigger erythropoiesis
What are some of the clinical signs you would see in anaemia secondary to chronic renal disease?
Clinical signs of chronic anaemia
Polyuria
Polydipsia
Vomiting
Decreased appetite
Weight loss
i.e. signs of chronic renal disease
Give an example of an endocrine disease that causes secondary failure of erythropoiesis
Hypothyroidism
How does hypothyroidism cause secondary failure of erythropoiesis?
Hypothyroidism causes decreased thyroid hormone production which causes depression of bone marrow activity, iron deficiency and vitamin B12 and folate deficiency
What are some of the clinical signs you would see in anaemia secondary to hypothyroidism?
Clinical signs of chronic anaemia
Dermatological disease
i.e. signs of hypothyroidism
What are the main causes of iron deficiency anaemia?
Chronic external bleeding or internal gastrointestinal bleeding
Chronic inflammation
Which further testing should you do to investigate iron deficiency anaemia?
Parastite screening
Ultrasound to investigate for lesions
What is regenerative anaemia?
Regenerative anaemia is where the bone marrow responds to a decrease in erythrocytes through producing more erythrocytes and prematurely releases immature erythrocytes
What are the two main forms of regenerative anaemia?
Haemolytic anaemia
Haemorrhagic anaemia
What are the distinguising clinical signs of haemolytic anaemia?
Jaundice
Haemaglobinuria
Hepato-splenomegaly
Pyrexia
Chocolate brown mucous membranes (oxidative damage)
What are the two forms of haemolysis?
Extravascular haemolysis
Intravascular haemolysis
What is extravascular haemolysis?
Extravascular haemolysis is where erythrocytes are engulfed by macrophages in the spleen and liver
What is intravascular haemolysis?
Intavascular haemolysis is where erythrocytes are bound to by complement and lysed by the membrane attack complex (MAC), which is a series perforin proteins which forms pores in the erythrocyte membrane causing haemolysis
What is a key clinical sign of intravascular haemolysis?
Haemaglobinuria as when erythrocytes are lysed within the blood vessel haemoglobin will be released into the blood and excreted in the urine
List five possible causes of haemolytic anaemia
Immune-mediated
Infection
Oxidative injury
Metabolic disorders
Congenital disorders
What is the difference between primary immune-mediated haemolytic anaemia (IMHA) and secondary immune-mediated haemolytic anaemia (IMHA)?
Primary IMHA is an autoimmune response against the natural antigens present on the erythrocytes, whereas secondary IMHA is caused by molecular mimicry where infectious or chemical agents trigger autoimmunity by binding to the erythrocytes
Which bacteria can cause secondary immune-mediated haemolytic anaemia (IMHA)?
Leptospirosis
Haemoplasma
Which two parasites can cause secondary immune-mediated haemolytic anaemia (IMHA)?
Babesia
Leishmania
Which two drugs can cause secondary immune-mediated haemolytic anaemia (IMHA)?
Sulphonamides
Penicillin
Which three neoplasias can cause secondary immune-mediated haemolytic anaemia (IMHA)?
Lymphoma
Leukaemia
Multiple myeloma
What is feline infectious anaemia?
Feline infectious anaemia is a haemolytic anaemia caused by mycoplasmas and haemoplasmas which cause secondary immune-mediated haemolysis and direct haemolysis
Which three mycoplasmas cause feline infectious anaemia?
Mycoplasma haemofelis
Mycoplasma haemonintum
Mycoplasma turicenis
How do you diagnose feline infectious anaemia?
Blood smears
PCR
What would you see on blood smear from a cat with feline infectious anaemia?
Mycoplasma within the erythrocytes
It is important not to get these confused with Howell-jolly bodies which are nucleur remnants seen in reticulocytes
(T/F) Cats with feline infectious anaemia can test Coombs positive
TRUE. Thus it is important to also do a blood smear and PCR to detect if there are any mycoplasma present so you can treat the mycoplasmas appropriately and not just the IMHA
What are two key signs of oxidative injury induced haemolytic anaemia on bloods smears?
Eccentrocytes
Heinz bodies
Both signs of denatured haemoglobin
What is another name used to describe haemolytic anaemia caused by oxidative injury?
Heinz body anaemia
What is a key clinical sign of oxidative injury induced haemolytic anaemia?
Chocolate brown blood and mucous membranes due to methaemaglobinaemia
List things that can cause oxidative injury if ingested
Paracetamol toxicity
Onion toxicity
Garlic toxicity
Zinc toxicity
Propofol toxicity (in cats)
Diabetes mellitus (rare)
Hepatic lipidosis (rare)
Which congential disease can cause haemolytic anaemia?
Erythrocyte enzymopathies
Very rare
What are the distinguishing clinical signs of haemorrhagic anaemia?
External bleeding - such as meleana and haematuria
Internal bleeding - such as signs of haemoabdomen, haemothorax
Hypovolaemia
Evidence of a haemostatic disorder - ecchymoses, petechiae, haematomas
Which six questions should you consider when diagnosing anaemia in small animals?
How severe is the anaemia?
Is the anaemia regenerative or non-regenerative?
What do the erythrocytes look like on a blood smear?
Could the anaemia be secondary to a haemostatic disorder?
Are any other cell lines affected?
Is there biochemical evidence of underlying disease?
Which laboratory test can be done to determine the severity of an anaemia?
Packed cell volume (PCV)
It is important to combine this with assessing the clinical signs
Which PCV range indicates a mild anaemia?
PCV of 30 - 39%
Which PCV range indicates a moderate anaemia?
PCV of 20 - 30%
Which PCV range indicates a severe anaemia?
PCV of less than 20%
What are signs of non-regenerative anaemia on a blood smear?
There are often no changes on a blood smear in patients with non-regenerative anaemia
What are three key signs of regenerative anaemia on a blood smear?
Anisocytosis
Polychromasia
Nucleated erythrocytes
What is anisocytosis?
Anisocytosis is a term used to describe when red blood cells are of different sizes on a blood smear
What is polychromasia?
Polychromasia describes a variation in colour of red blood cells on a blood smear, indicating the presence of prematurely released immature red blood cells - typically reticulocytes
What should the absolute reticulocyte count be for there to be an appropriate regenerative response?
More than 60 x 10^9/litre
What should the reticulocyte percentage be for there to be an appropriate regenerative response?
The reticulocyte percentage should be more than 50% of the expected response
i.e if the PCV is 20%, the reticulocyte percentage should be 10% or over
What are red cell indicies?
Mean corpuscular volume (MCV)
Mean corpuscular haemoglobin concentration (MCHC)
What is mean corpuscular volume (MCV)?
MCV is the average size of the erythrocytes
What can MCV be classified as?
Macrocytic
Normocytic
Microcytic
What is mean corpuscular haemoglobin concentration (MCHC)?
MCHC is the average concentration of haemaglobin per erythrocyte
What can MCHC be classified as?
Normochromic
Hypochromic
Which red cell indicies can indicate anaemia secondary to iron deficiency?
Microcytic hypochromic
What is a key signs of anaemia secondary to iron deficiency on blood smear?
Area of central pallor on the erythrocytes
What are the distinguishing laboratory features of anaemia caused by primary bone marrow disease?
Non-regenarative anaemia on blood smear
Severe anaemia on PCV
Normocytic, normochromic red cell indicies
Maybe pancytopenia or bicytopenia
Which further test would you do if you suspect anaemia due to primary bone marrow disease?
Bone marrow assessment
What are the distinguishing laboratory features of immune-mediated haemolytic anaemia (IMHA)?
Regenerative anaemia on blood smear
Spherocytosis on blood smear
Macrocytic, hypochromic red cell indicies
Leukocytosis IMHA is an inflammatory disease process
Hyperbilirubinaemia
Evidence of organ dysfunction
Why does immune-mediated haemolytic anaemia (IMHA) present with macrocytic, hypochromic red cell indicies?
Immune-mediated haemolytic anaemia (IMHA) is a regenerative anaemia meaning there are going to be larger, immature cells explaining the macrocytosis and these immature cells tend to have a lower concentration of haemoglobin, explaining the hypocromic value
Which two tests can you do to confirm a diagnosis of immune-mediated haemolytic anaemia (IMHA)?
Slide-agglutination test
Coombs test
What further investigation can you do after diagnosing immune-mediated haemolytic anaemia (IMHA)?
Identify and address any underlying disease processes that could be causing the IMHA, such as screening for parasites, thoracic and abdominal radiographs to detect any neoplasia, urinalysis, culture and sensitivity, PCR, drug history
How do you manage and treat immune-mediated haemolytic anaemia?
Blood transfusion if necessary
Immunosuppresive drug therapy
Oxygen supplementation
Goal directed fluid therapy
Administer clopidogrel, heparin or low dose aspirin to prevent the risk of thromboembolisms
Treat underlying cause if a secondary IMHA
How do glucocorticoids work as immunosuppressive drug therapy for managing immune-mediated haemolytic anaemia (IMHA)?
Glucocorticoids interfere with the expression and function of Fc receptors on macrophages and thus reduce phagocytosis of erythrocytes
Which two glucocorticoids are used as first line immunosupporesive therapy for immune-mediated haemolytic anaemia (IMHA)?
IV dexamethosone (for acute emergency treatment)
Oral prednisolone (for management treatment),
Which second line immunosuppressive drugs can be used to prevent further antibody production against erythrocytes?
Ciclosporin (si-clo-sporin)
Azathioprine
Mycophenolate mofetil
Which second line immunosuppressive drug is liscenced in the UK?
Ciclosporin
What can you use as immunosuppressive therapy for refractory cases of immune-mediated haemolytic anaemia (IMHA)?
Human intravenous immunoglobulins
What is the prognosis for immune-mediated haemolytic anaemia (IMHA)?
Mortality rate of 25 - 70%
What are the causes of death due to immune-mediated haemolytic anaemia (IMHA)?
Refractory to treatment
Hypoxaemia
Pulmonary thromboembolism
Disseminated intravascular coagulation (DIC)
Why are IMHA patients prone to thromboembolisms and DIC?
Immune-mediated haemolytic anaemia (IMHA) is an inflammatory disorder which results in a hypercoagulable state which increases the risk of thromboembolisms and disseminated intravascular coagulation (DIC)
What are the distinguishing laboratory features of haemorrhagic anaemia?
Regenerative or pre-regenerative anaemia on blood smear
Schistocytosis on blood smear
Hypoproteinaemia due to losing whole blood
Evidence of a haemostatic disorder e.g. thrombocytopenia, prolonged clotting times
What is present on this haematology slide?
Rouleaux
What is indicated by rouleaux?
Rouleaux are commonly seen in cats, and can indicate high globulin levels
What is present on this haematology slide?
Autoagglutination
What is indicated by autoagglutination?
Autoagglutination indicates immune mediated disease
