Hematopoietic disorders and classification of anemia

Question 1

Function of RBC

Answer 1

Transport and protect hemoglobin
Transport O2 from the lungs to the tissues and CO2 from the tissues to the lungs to be expired
In a normal animal, the daily production of RBCs equals the daily loss due to the destruction of aged cells

Question 2

Anemia is and can be due to

Answer 2

Anemia is when the oxygen-carrying capacity of erythrocytes is reduced. This may be due to:
-Reduced numbers of circulating RBCs
-Reduced PCV
-Reduced hemoglobin concentration
-If RBC production is decreased or RBCs are being lost
It is only a symptom of another disease process, there is always an underlying cause

Question 3

Classification of anemia

Answer 3

There are a number of ways in which anemia can be classified:
By bone marrow response
By red blood cell size and hemoglobin concentration
MCV and MCHC
By the underlying etiology
Classification based on bone marrow response and RBC parameters will help to identify the cause of the anemia

Question 4

Tests used to determine the cause of anemia

Answer 4

Reticulocyte count
Erythrocyte indices
PCV
RBC morphology
Plasma color and turbidity
Total plasma protein concentration

Question 5

Specialty lab results used for diagnosis of anemia

Answer 5

Coombs test
Serum iron levels
Fecal examination for GI blood loss
Antigen or antibody tests for specific diseases
FeLV, FIV, EIA, feline hemotropic mycoplasmosis, blood borne parasites
Biochemical assays
Bone marrow evaluation

Question 6

How do you use the bone marrow response to classify anemia

Answer 6

The most clinically applicable classification system
Classifies the anemia as either regenerative or nonregenerative
The bone marrow’s response to anemia should be to increase RBC production and to release immature RBCs
Assessment of the bone marrow response is based on the number of immature RBCs present in circulation
Polychromatic RBCs or nucleated RBCs
Determined by performing a reticulocyte count

Question 7

Regenerative anemia is

Answer 7

The presence of reticulocytes means that the bone marrow is responding, therefore there is a regenerative response
Anemia is likely due to either hemorrhage or hemolysis
It takes about 4–7 days for immature RBCs to appear in peripheral blood after blood loss or destruction
The exception is in horses
A patient is considered to have an adequate bone marrow response when their reticulocyte count is equal to or greater than the expected value for the patient’s PCV

Question 8

Regenerative anemia in horses

Answer 8

Horses do not release polychromatic cells from the bone marrow, therefore a bone marrow aspirate is necessary to evaluate reticulocyte numbers
They will release macrocytic, normochromic cells
Reticulocyte counts of greater than 5% from the bone marrow aspirate indicates a regenerative anemia

Question 9

Nen-regenerative anemia

Answer 9

A nonregenerative anemia is defined as a low RBC mass with no evidence of a bone marrow response in the peripheral blood
No polychromasia or reticulocytes
RBCs are normochromic
A bone marrow aspirate is indicated after endocrine and metabolic causes of a nonregenerative anemia have been ruled out
Attributed to bone marrow dysfunction, or the inability of the bone marrow to produce RBCs
Further classified based on whether granulopoiesis and thrombopoiesis are also involved in the bone marrow dysfunction

Question 10

Some causes of nonregnerative anemia are

Answer 10

Iron deficiency
Ehrlichiosis
Drug toxicity
Histoplasmosis
Hypothyroidism
Renal insufficiency
Chronic disease
Chronic infection
Chronic liver disease
Nutritional deficiencies or intestinal malabsorption
Toxins-lead
Hormonal imbalances

Question 11

Classification by RBC Size and Hemoglobin Concentration

Answer 11

Classifies anemia as either normocytic, macrocytic, or microcytic
Uses MCV and MCHC
Macrocytic anemia
-Usually seen with regenerative anemia
Microcytic anemia
-Almost always the result of an iron deficiency
Animals with a normocytic anemia usually have a nonregenerative anemia or a preregenerative anemia
-Preregenerative- it is too early in the disease course to see a bone marrow response
Anemias can also be classified as either hypochromic or normochromic
-A hyperchromic state is not possible
Polychromatic RBCs contain less hemoglobin than a mature RBC, therefore they are technically considered hypochromic (though they don’t appear this way)
-They appear to be hyperchromic due to the staining of the nuclear remnants
Hypochromic, microcytic anemia is almost always due to iron deficiencies
-Low MCV and MCHC
All other anemias are normochromic

Question 12

Classification of etiology of anemia

Answer 12

Hemolytic
Hemorrhagic
Iron deficiency
Production disorders
Or combinations of the above

Question 13

Hemolytic anemia is and due to

Answer 13

Due to erythrocyte destruction
Theses animals usually develop a regenerative anaemia
During the pre regenerative phase they will have a normocytic, normochromic anemia
RBC destruction may be intravascular or extravascular
It is caused by immune-mediated destruction, erythrocyte parasites, bacterial and viral agents, and toxin exposure

Question 14

Clinical signs of hemolytic anemia

Answer 14

Lethargy
Splenomegaly
Fever
Icterus
Pale mucous membranes
Dyspnea
Tachycardia
Systolic heart murmur
Syncope

Question 15

Laboratory findings with hemolytic anemia

Answer 15

Decreased PCV
Decreased red blood cell count
Decreased hemoglobin concentration
Inflammatory leukogram
Hemoglobinemia, hemoglobinuria, hyperbilirubinemia & bilirubinuria
Positive Coomb’s Test
With immune mediated forms of hemolytic anemia

Question 16

Immune mediated hemolytic anemia is and due to

Answer 16

Due to increased red cell destruction
Occurs as a result of antibodies directed against the RBC itself or immune complexes that attach to the RBC
It will produce a marked regenerative anemia
This is the most common cause of hemolytic anemia in dogs
Common in Cocker Spaniels, Poodles & Collies
Has also been seen in horses, cattle and cats

Question 17

What does a blood smear with immune mediate hemolytic anemia look like

Answer 17

Spherocytes**
Agglutination
+/- Thrombocytopenia
Increased polychromasia

Question 18

Neonatal isoerythrolysis is and due to

Answer 18

A form of IMHA
Due to antibodies from the dam against the neonate’s RBCs
In most species, there must be either previous exposure to blood products or a previous pregnancy
Mismatched blood transfusions cause a similar reaction
Most common in horses & mules, also seen in kittens
Neonates are healthy when born and become weak, lethargic, pale, anemic, icteric and dyspneic within 12 hours to 4 days post partum

Question 19

Lab findings for neonatal isoerytholysis

Answer 19

Coomb’s test positive
Dam can be tested 2 weeks prior to parturition to predict the likelihood of neonatal isoerythrolysis
Equine–mares most frequently develop antibodies to blood types Aa and Qa
Feline–type A or AB kittens born to type B queens

Question 20

Erythrocyte parasites common in sk are

Answer 20

Mycoplasma haemofelis
Anaplasma
Babesia
Ehrlichia

Question 21

Common infectious agents that cause anemia

Answer 21

Most of these pathogens can cause at least two types of anemia
FeLV
Leptospira
EIA virus

Question 22

Heinz body anemia is and caused by

Answer 22

Oxidative damage to the RBC
Cats are more susceptible than other domestic species
Can be due to medications, chemicals, plants, inherited enzyme deficiencies and nutritional deficiencies or toxicities

Question 23

Plants that may cause heinz body anemia

Answer 23

Allium family: onions & garlic
Brassica family: cabbage, kale & canola seed

Question 24

Common drugs that cause heinz body anemia

Answer 24

Acetaminophen
Propylene glycol
Zinc and copper toxicity
Methylene blue

Question 25

Other conditions that may cause heinz bodies

Answer 25

Diabetes
Hyperthyroidism
Lymphoma
Hypophosphatemia
EIA
Bacterial infections (clostridial)
Inherited membrane defects
Metabolic disorders

Question 26

Hemorrhagic anemia is caused by

Answer 26

Can be external or internal
External blood loss causes loss of RBCs, iron and plasma proteins
Internal blood loss does not lead to loss of protein or iron
Some RBCs will be re-absorbed and return to circulation
Chronic or acute

Question 27

Common causes of hemorrhagic anemia

Answer 27

Trauma
Surgical losses
Parasites (fleas, ticks, hookworms)
Coagulopathy, thrombocytopenia, thrombopathia
Neoplasia
Cystitis
Bleeding lesions– GI ulceration, IBD

Question 28

Lab findings with hemorrhagic anemia

Answer 28

Decreased PCV
+/- Decreased plasma proteins
Increased polychromasia–not acutely
Normal RBC morphology–acute cases

Question 29

Hemangiosarcoma is

Answer 29

Malignant vascular tumours
Most commonly located in the spleen, liver & right atrium
Spreads quickly to the lungs & other organs

Question 30

Lab results with hemangiosarcoma

Answer 30

Polychromasia
Transient hypoproteinemia
Acanthocytes and schistocytes
Thrombocytopenia
Possibly DIC-BAD

Question 31

Iron deficiency anaemia is

Answer 31

Chronic blood loss results in iron deficiency anemia
In adults, iron deficiency anemia is almost always due to blood loss
In neonates, iron deficiency anemia is almost always due to insufficient iron intake
Affects all neonatal domestic species
Piglets are at a highest risk because they do not have access to iron rich soil–often given injections shortly after birth
Common in dogs
Rare in cats and horses

Question 32

Laboratory Findings With Iron Deficiency Anemia

Answer 32

Decreased MCV**
Decreased MCHC
Increased total iron binding capacity (TIBC)– referred out test
Measurement of serum ferritin levels– reflects total iron stores in the body

Question 33

Blood smear will show what with iron deficiency anemia

Answer 33

Increased central pallor
Pale RBCs, often with just a ring of hemoglobin
Keratocytes
Schistocytes
Folded RBCs
Microcytosis
Thrombocytosis in ≈ 50% of cases

Question 34

Production disorders cause anemia by

Answer 34

Due to reduced rates of erythropoiesis or defective erythropoiesis
Generally results in a normochromic anemia
Nonregenerative

Question 35

What production disorders can cause anemia

Answer 35

Chronic renal disease, hypothyroidism, hypoadrenocorticism, bracken fern poisoning, iron and copper deficiency, parvovirus, and lead toxicity

Question 36

Chronic renal failure and anmeia

Answer 36

Usually results in a moderate to severe anemia
Nonregenerative
Normocytic
The more severe the kidney failure, the more severe the anemia
Occurs due to lack of erythropoietin production by the kidneys, particularly in dogs and cats

Question 37

Hypothyroidism and anemia

Answer 37

Results in a mild, nonregenerative, normocytic anemia
Hematocrit of ≈ 0.30 L/L
Once the hypothyroidism is addressed, the anemia will resolve
Believed to be due to a lower metabolic rate

Question 38

Hypoadrenocorticism and anemia

Answer 38

Results in a mild, nonregenerative, normocytic anemia
Often masked by dehydration
Dehydration causes the PCV to be artificially increased

Question 39

Reticulocytes are

Answer 39

Reticulocytes →immature RBCs that contain organelles

Question 40

What do reticulocytes look like

Answer 40

Cells are macrocytic and blue-purple staining with Wrights stain-polychromasia
New Methylene Blue stain makes the organelles stain dark blue and the cell appears green

Question 41

2 types of reticulocytes

Answer 41

punctate and aggregate
It is aggregate reticulocytes that appear as polychromatophilic cells on blood smears (Wright’s stain)
Cats generally have higher numbers of punctate reticulocytes than aggregate reticulocytes

Question 42

Normal reticulocyte values in health:

Answer 42

Bovine, Ovine and Caprine–0%
Equine– 0%
Porcine– 0-2%
Canine– 0.5-1.5%
Feline– 0.5-1%
Rabbit, Guinea Pig, Rat, Mouse– 2-4%

Question 43

What is reticulocyte counts used for

Answer 43

Used to determine whether the animal is responding to an anemic event
Regenerative Anemia–the bone marrow is responding by releasing immature RBCs
Non- Regenerative Anemia– the bone marrow is not responding to the anemia

Question 44

How to see reticulocytes

Answer 44

Always report any increase of polychromasia or lack of polychromasia
A reticulocyte stain should be performed on all anemic animals (except horses)
Performed by some automated analyzers

Question 45

How to stain to see reticulocytes and how to estimate

Answer 45

Place a few drops of blood and an equal number of drops of new methylene blue stain in a small test tube
Let sit for 10-15 minutes
Use a drop of the solution to prepare a blood smear
Examine the smear as is, or counterstain with Wright’s stain
1000 RBCs are counted under the oil immersion lens

Question 46

How to calculate reticulocyte counts

Answer 46

% of RBCs that are reticulocytes
% Reticulocytes = Number of retics counted/1000 RBCs x 100

Question 47

How are reticulocytes results read

Answer 47

Results are interpreted according to the degree of anemia for the following reasons:
Anemic animals have fewer mature erythrocytes
Reticulocytes are released earlier and persist longer in anemic animals

Question 48

How to preform a corrected reticulocyte count

Answer 48

Corrected Reticulocyte Count = Reticulocyte % x (PCV/Normal PCV)
Use a normal PCV of 45% for dogs, and 35% for cats
Example: A dog has an observed reticulocyte percentage of 12% and a PCV of 15%. What is the corrected reticulocyte count?
Corrected Reticulocyte Count = 12% x (15%÷45%)= 4%

Question 49

Reticulocyte production index (RPI) is

Answer 49

RPI = Corrected Reticulocyte Count/Reticulocyte Maturation Time
Requires the use of the following reference chart

Question 50

45% PCV means what maturation time

Answer 50

1

Question 51

35% PCV means what maturation time

Answer 51

1.4

Question 52

25% PCV means what maturation time

Answer 52

2

Question 53

15% PCV means what maturation time

Answer 53

2.5

Question 54

Polycythemia is

Answer 54

Refers to an increase in the concentration of erythrocytes in the blood (increased PVC, increased red cell count, or increased hemoglobin concentration)
Erythrocytosis is the preferred term when only the RBCs are affected

Question 55

Polycythemia can be due to

Answer 55

May be due to dehydration, splenic contraction (exercise or epinephrine release–fear, pain, or excitement), hypoxia, or increased erythropoietin production

Question 56

polycythemia looks like and most common in

Answer 56

In some instances, the RBCs proliferate uncontrollably
There is a normal maturation sequence and normal proportions of immature to mature cell numbers, but the total number of RBCs is increased
Most commonly seen in dogs and cats, but also affects horses, cattle and llamas
Always make note if the patient is DEHYDRATED, EXCITED, FEARFUL OR PAINFUL at the time that the sample was collected to help to identify the reason for an increased PCV