CHAPTER 32. Hematology
Rebecca S. McConnico
ANEMIA
I. Regenerative anemia
A. Horses do not release reticulocytes into circulation in response to an acute hemorrhagic or hemolytic episode
B. Increased mean cell volume and red cell distribution width after hemorrhage or hemolysis are unreliable indicators of regeneration
C. Best method of assessing the equine erythroid regenerative response is determination of bone marrow myeloid-erythroid (M:E) ratio or bone marrow reticulocyte count
1. M:E ratio of 0.5 is consistent with erythrocyte regeneration
a. Normal equine marrow contains approximately 3% reticulocytes
b. Following acute severe hemorrhage, this may increase to 66%
2. If bone marrow analysis is not an option, peripheral blood packed cell volume (PCV) may be monitored to assess regeneration. Accelerated bone marrow red cell production should be evident by 3 to 7 days after acute hemorrhage, with an average increase in PCV of 0.5% to 1.0% per day
II. Causes of regenerative anemia
A. Blood loss
B. Red blood cell (RBC) destruction
1. Immune mediated
2. Neonatal isoerythrolysis
3. Heinz body anemia (oxidative damage)
4. RBC parasites
III. Intravascular vs. extravascular hemolysis
A. Intravascular hemolysis
1. Hemoglobin from the lysed erythrocytes is released directly into the plasma
2. Excess hemoglobin is bound to haptoglobin
3. As the binding capacity of haptoglobin is exceeded, gross hemoglobinemia develops
4. Some excess hemoglobin is taken up by mononuclear phagocytes and metabolized to bilirubin
5. Other hemoglobin is filtered through the renal glomerulus, resulting in hemoglobinuria and potential renal tubular damage
6. Plasma hemoglobin concentrations are approximately one third of the PCV
7. Intravascular hemolysis → plasma hemoglobin concentration exceeds one third of the PCV and plasma bilirubin concentrations are increased
8. Intravascular hemolysis → increased mean corpuscular hemoglobin (MCH) and MCH concentration
B. Extravascular hemolysis
1. Damaged RBCs are removed from circulation by mononuclear phagocytes
2. Gross hemoglobinemia and hemoglobinuria do not occur
3. Hemoglobin is degraded directly into bilirubin inside the phagocytic cell, and serum bilirubin concentrations increase
IV. Blood loss
A. There are many causes of blood loss; most are evident
B. Treatment of acute severe hemorrhage (loss of 15% to 30% of total blood volume)
1. The most important aspects of therapy are controlling the hemorrhage and replacing blood volume
a. Apply direct pressure to the site or ligate the offending vessel(s)
b. Control of internal hemorrhage
2. Use some form of volume replacement therapy if the horse is tachycardic with poor peripheral perfusion
a. Hypertonic saline: Hypertonic saline at 4 to 6 mL/kg administered IV over 15 minutes, followed within a few hours by isotonic fluid administration in sufficient quantity to replace estimated total body fluid deficits
b. Isotonic fluids: Total volume should exceed the estimated volume of blood loss by a factor of 2 to 3
c. Whole-blood transfusion: ∼1 mL of whole blood/lb of body weight should increase the recipient horse’s PCV by 1%. Therefore, 1 L of whole blood should increase the PCV of a 450 kg horse by approximately 1%
V. Heinz body anemia
A. Acute or chronic RBC destruction
1. Caused by oxidative denaturation of hemoglobin with subsequent formation of Heinz bodies within the RBCs
2. Produces cells that are readily removed from the circulation by either intravascular hemolysis or via macrophages as part of the reticuloendothelial system
1. Known toxins, drugs, and chemicals associated with Heinz body production function as electron acceptors and act as an artificial link between cell components and the direct oxidative action of molecular O 2 in the RBCs
2. Denatured hemoglobin formed through this reaction precipitates in the form of Heinz bodies and attaches to the RBC membrane, causing either loss of critical ionic composition with resultant intravascular hemolysis or deformability changes with subsequent premature RBC removal by the spleen
C. Clinical signs
1. May affect any age, sex, or breed but is uncommon in adults
2. Exercise intolerance
3. Weakness
4. Pale or icteric mucous membranes
5. With or without fever
6. With or without tachypnea
7. With or without tachycardia
8. Holosystolic heart murmur
9. Abdominal pain (ischemia)
10. Hemoglobinuria
11. Rectal examination: Enlarged spleen
12. Severe debilitation and death in severe cases
13. Necropsy: Enlarged liver and spleen; pale or icteric tissues
D. Causes
1. Toxicosis
a. Phenothiazine
b. Wilted red maple leaves
(1) Leaves contain an uncharacterized toxin that oxidizes ferrous (Fe++) iron in the normal hemoglobin molecule to the ferric (Fe++) form
(2) Ferric form of hemoglobin, known as methemoglobin, is incapable of carrying oxygen to the tissues
(3) Normal blood methemoglobin concentration is less than 1%. Horses that have ingested wilted red maple leaves may have methemoglobin concentrations greater than 25%. Excess methemoglobin results in a brownish discoloration to blood and tissues. Oxidant stress to erythrocytes also results in the formation of disulfide linkages in the protein component of the hemoglobin molecule with resultant denaturation and precipitation of the molecule. Denatured hemoglobin is seen as spherical, refractile Heinz bodies attached to the erythrocyte membrane. Heinz bodies increase osmotic fragility, resulting in intravascular hemolysis and may also enhance cell clearance from circulation by mononuclear phagocytes
c. Wild onions
2. Antigen: RBCs
E. Diagnosis
1. Differential diagnosis
a. Hemorrhage
b. Heinz body anemia (red maple leaf toxicosis, onion toxicosis, phenothiazine toxicosis)
c. Equine infectious anemia
d. Equine piroplasmosis
e. Equine granulocytic ehrlichiosis
f. Lymphosarcoma
g. Purpura hemorrhagica
2. Complete blood cell count (CBC), biochemistry, and urinalysis
a. PCV less than 20%
b. Heinz bodies on direct blood smear
c. With or without neutrophilic leukocytosis
d. Negative Coombs’ test
e. Elevated total bilirubin (indirect >>>> direct)
f. Increased MCH suggests the presence of intravascular hemolysis
g. Bilirubinuria
h. Occult blood positive (no microscopic hematuria)
3. Other laboratory tests
a. Negative direct antiglobulin test (Coombs’)
b. Increased osmotic fragility
c. Bone marrow aspirate reveals a diffuse regenerative erythron (M:E ratio less than 0.5)
d. Heinz bodies are best visualized with new methylene-blue stain of a wet-mount preparation of blood (Heinz bodies appear as bluish green, oval-to-serrated refractile granules located near RBC margin or protruding from the cell)
e. Elevated blood urea nitrogen (BUN) level if hemoglobinuric nephrosis is present
f. Methemoglobin test if mucous membranes or urine are brown-tinged
4. Imaging
a. Splenic-hepatic ultrasound: Splenic or hepatic enlargement; may show hyperechoic or hypoechoic. Some loss of architecture as a result of increased fluid component
b. Radiographs: Thorax is usually within normal limits
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