Exam 2: Regenerative Anemia - Hemolysis

Question 1

What are the signs of intravascular hemolysis?

Answer 1

Reticulocytosis
Normal to increased PP
Neutrophilia
Monocytosis
Platelet abnormalities
Hyperbilirubinemia
Splenomegaly
Heinz bodies, RBC parasites, poikilocytes

Question 2

What are the signs of extravascular hemolysis?

Answer 2

Decreased RBC deformability
Decreased RBC metabolism
Increased macrophage phagocytosis
Immune-mediated disease

Question 3

What causes decreased erythrocyte deformability?

Answer 3

Fragmentation hemolysis (DIC, HW, vasculitis, hemangiosarcoma, schistocytes)
Spherocytes
Oxidative damage (Heinz bodies, keratocytes, eccentrocytes)
Parasites

Question 4

What causes decreased erythrocyte metabolism?

Answer 4

Aging
Phosphofructokinase deficiency
Pyruvate kinase deficiency

Question 5

What causes increased macrophage phagocytic activity?

Answer 5

Hypersplenism
Hemophagocytic syndromes
Malignant histiocytosis

Question 6

What is the basis behind IMHA?

Answer 6

Ab and complement bind Ag on RBCs
Type II Hypersensitivity Reaction

Question 7

What are the signs of “warm” IMHA?

Answer 7

Depression, lethargy
Weakness, syncope
Pale mm, icterus
Spleno-hepatomegaly
Lymphadenopathy
Pyrexia
Vomiting
PTE, DIC

Question 8

What are the signs of “cold” IMHA?

Answer 8

Cyanosis
Necrosis
Gangrene
Occurs on ear tips, nose, tail, distal extremities

Question 9

What are the 3 subcategories of IMHA and how does each work?

Answer 9

Alloimmune: antibody from another member of the same species reacts with an antigen on the affected individual’s cells
Primary: antibody is directed against a self-antigen
Secondary: antibody is directed against an absorbed antigen on the cells

Question 10

What are the 2 main examples of alloimmune hemolytic anemia and how do they work?

Answer 10

Mismatched blood transfusions: Ab in the donor’s serum binds to the recipient’s RBCs, minor cross match agglutinates
Neonatal isoerythrolysis: maternal Ab reacts to paternally derived antigens on neonate’s RBCs

Question 11

What is primary IMHA?

Answer 11

AKA idiopathic IMHA, autoimmune HA (AIHA)
Primarily in dogs
IgM, IgG +/- IgA vs RBC membrane Ag
Causes: idiopathic, methyldopa

Question 12

What causes secondary IMHA?

Answer 12

Infection
Inflammation
Pharmaceuticals
Abnormal T cell function
Paraneoplastic syndromes

Question 13

What does IMHA look like hematologically?

Answer 13

Decreased RBC count
Decreased PCV
Decreased Hgb
Increased MCV
Increased reticulocytes
Autoagglutination
Spherocytes
Neutrophilia
Monocytosis
Platelet abnormalities

Question 14

Overall, what are the diagnostic tests for IMHA?

Answer 14

Chemistry panel
Urinalysis
Agglutination
Bone Marrow
Coomb’s test
Antinuclear antibody
Test for underlying etiology
Always examine a blood smear

Question 15

What values in a chemistry panel can diagnose IMHA?

Answer 15

Increased liver enzymes
Increased bilirubin

Question 16

What values in a urinalysis can diagnose IMHA?

Answer 16

Intravascular = hemoglobinuria and proteinuria
Extravascular = bilirubinemia

Question 17

How does agglutination testing for IMHA work?

Answer 17

Mix EDTA blood with saline on a slide
Examine slide at RT and 4C

Question 18

What does the bone marrow tell us when diagnosing IMHA?

Answer 18

Not necessary with regenerative anemia
Erythroid hyperplasia indicates regeneration
Myelofibrosis or RBC aplasia may be seen with nonregenerative disease

Question 19

How does the Coomb’s test work in diagnosing IMHA?

Answer 19

Detects IgG, IgM, or C3 bound to RBCs
Combine with whole blood with species specific reagents and look for agglutination

Question 20

What can cause false positives on a Coomb’s test?

Answer 20

Recent transfusion

Question 21

What can cause false negatives on a Coomb’s test?

Answer 21

Ab vs precursor not cell
Drug-dependent
Steroid administration

Question 22

How does antinuclear antibody testing work for IMHA?

Answer 22

Detects Ig that binds to nuclear components

Question 23

What signalments are associated with IMHA?

Answer 23

Mammals
Females > Males
Middle-aged
Sheepdog, spaniels, collies, poodle, setter, GSD, whippet

Question 24

What does intravascular hemolysis look like hematologically?

Answer 24

Reticulocytosis
Hemoglobinemia (icterus, hyperchromasia, high MHC, decreased serum haptoglobin and hemopexin)
Hemoglobinuria
Hemosiderinuria
Hyperbilirubinemia
Heinz bodies, RBC parasites, poikilocytes

Question 25

What is the pathogenesis of intravascular hemolysis?

Answer 25

Complement-mediated RBC lysis
Osmotic hemolysis
Membrane damage
Toxins

Question 26

What is osmotic hemolysis and what values can be seen in the blood values?

Answer 26

Extracellular and intracellular osmolarity are imbalanced
Hypophosphatemia
RBC membrane damage
Hypotonic IV fluids

Question 27

What is the pathogenesis of physical membrane damage?

Answer 27

Fibrin: DIC, vasculitis, hemangiosarcoma, HW
Intracellular parasites

Question 28

What is the pathogenesis of oxidative membrane damage?

Answer 28

Denatures Hb
Cross-links RBC membrane proteins
Forms metHb

Question 29

What are the main toxins that cause oxidative damage to membranes?

Answer 29

Red maple leaves (horses)
Zinc (dogs)
Acetominophen (cats)
Castor beans (ricin)
Snake venom
Bacterial toxins
Uremic toxins

Question 30

What is methemoglobin and the methemoglobin reductase pathway?

Answer 30

Reduced methemoglobin to hemoglobin
Methemoglobin contains oxidized iron and cannot transport oxygen
Increased levels can cause cyanosis and exercise intolerance
Blood looks brown (not red) when placed on white absorbent paper

Question 31

What causes methemoglobinemia to occur?

Answer 31

Deficiency in NADH methemoglobin reductase
Deficiency in NADPH methemoglobin reductase
Nitrate-accumulating plants (ruminants)