Hematopoietic disorders and classification of anemia Flashcards
Function of RBC
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
Anemia is and can be due to
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
Classification of anemia
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
Tests used to determine the cause of anemia
Reticulocyte count
Erythrocyte indices
PCV
RBC morphology
Plasma color and turbidity
Total plasma protein concentration
Specialty lab results used for diagnosis of anemia
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
How do you use the bone marrow response to classify anemia
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
Regenerative anemia is
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
Regenerative anemia in horses
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
Nen-regenerative anemia
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
Some causes of nonregnerative anemia are
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
Classification by RBC Size and Hemoglobin Concentration
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
Classification of etiology of anemia
Hemolytic
Hemorrhagic
Iron deficiency
Production disorders
Or combinations of the above
Hemolytic anemia is and due to
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
Clinical signs of hemolytic anemia
Lethargy
Splenomegaly
Fever
Icterus
Pale mucous membranes
Dyspnea
Tachycardia
Systolic heart murmur
Syncope
Laboratory findings with hemolytic anemia
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
Immune mediated hemolytic anemia is and due to
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
What does a blood smear with immune mediate hemolytic anemia look like
Spherocytes**
Agglutination
+/- Thrombocytopenia
Increased polychromasia
Neonatal isoerythrolysis is and due to
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
Lab findings for neonatal isoerytholysis
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
Erythrocyte parasites common in sk are
Mycoplasma haemofelis
Anaplasma
Babesia
Ehrlichia
Common infectious agents that cause anemia
Most of these pathogens can cause at least two types of anemia
FeLV
Leptospira
EIA virus
Heinz body anemia is and caused by
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
Plants that may cause heinz body anemia
Allium family: onions & garlic
Brassica family: cabbage, kale & canola seed
Common drugs that cause heinz body anemia
Acetaminophen
Propylene glycol
Zinc and copper toxicity
Methylene blue
Other conditions that may cause heinz bodies
Diabetes
Hyperthyroidism
Lymphoma
Hypophosphatemia
EIA
Bacterial infections (clostridial)
Inherited membrane defects
Metabolic disorders
Hemorrhagic anemia is caused by
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
Common causes of hemorrhagic anemia
Trauma
Surgical losses
Parasites (fleas, ticks, hookworms)
Coagulopathy, thrombocytopenia, thrombopathia
Neoplasia
Cystitis
Bleeding lesions– GI ulceration, IBD
Lab findings with hemorrhagic anemia
Decreased PCV
+/- Decreased plasma proteins
Increased polychromasia–not acutely
Normal RBC morphology–acute cases
Hemangiosarcoma is
Malignant vascular tumours
Most commonly located in the spleen, liver & right atrium
Spreads quickly to the lungs & other organs
Lab results with hemangiosarcoma
Polychromasia
Transient hypoproteinemia
Acanthocytes and schistocytes
Thrombocytopenia
Possibly DIC-BAD
Iron deficiency anaemia is
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
Laboratory Findings With Iron Deficiency Anemia
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
Blood smear will show what with iron deficiency anemia
Increased central pallor
Pale RBCs, often with just a ring of hemoglobin
Keratocytes
Schistocytes
Folded RBCs
Microcytosis
Thrombocytosis in ≈ 50% of cases
Production disorders cause anemia by
Due to reduced rates of erythropoiesis or defective erythropoiesis
Generally results in a normochromic anemia
Nonregenerative
What production disorders can cause anemia
Chronic renal disease, hypothyroidism, hypoadrenocorticism, bracken fern poisoning, iron and copper deficiency, parvovirus, and lead toxicity
Chronic renal failure and anmeia
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
Hypothyroidism and anemia
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
Hypoadrenocorticism and anemia
Results in a mild, nonregenerative, normocytic anemia
Often masked by dehydration
Dehydration causes the PCV to be artificially increased
Reticulocytes are
Reticulocytes →immature RBCs that contain organelles
What do reticulocytes look like
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
2 types of reticulocytes
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
Normal reticulocyte values in health:
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%
What is reticulocyte counts used for
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
How to see reticulocytes
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
How to stain to see reticulocytes and how to estimate
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
How to calculate reticulocyte counts
% of RBCs that are reticulocytes
% Reticulocytes = Number of retics counted/1000 RBCs x 100
How are reticulocytes results read
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
How to preform a corrected reticulocyte count
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%
Reticulocyte production index (RPI) is
RPI = Corrected Reticulocyte Count/Reticulocyte Maturation Time
Requires the use of the following reference chart
45% PCV means what maturation time
1
35% PCV means what maturation time
1.4
25% PCV means what maturation time
2
15% PCV means what maturation time
2.5
Polycythemia is
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
Polycythemia can be due to
May be due to dehydration, splenic contraction (exercise or epinephrine release–fear, pain, or excitement), hypoxia, or increased erythropoietin production
polycythemia looks like and most common in
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
