Hemolytic Anemia

Question 1

What is hemolytic anemia?

Answer 1

When RBCs are destroyed

Question 2

What basic components indicate blood loss or hemolytic anemia?

Answer 2

1. regenerative anemia
2. macrocytic, hypochromic
3. polychromasia/reticulocytosis

Question 3

What extra things indicate hemolytic anemia rather than blood loss?

Answer 3

1. Hemogloinemia/hemoglobinuria
2. hyperbilirubinemia/bilirubinuria
3. Abnormal RBC morphology or parasites
4. Proteins within normal range because they are not being lost from the vasculature

Question 4

Intravascular vs extravascular hemolysis

Answer 4

Can be used to determine etiology of anemia
-intravascular generally poorer prognosis
-extravascular more common
*although both can be present

Question 5

What is intravascular hemolysis?

Answer 5

RBC destruction within blood vessels
-causes hemoglobinemia and hemoglobinuria (increased MCH and MCHC)
-may see hyperbilirubinemia and bilirubinuria over time

Question 6

Why is the free hemoglobin from RBC destruction (intravascular hemolysis) bad?

Answer 6

1. Hemoglobinuric nephropathy (kidneys filtering hemoglobin)
2. Thrombosis

Question 7

Extravascular hemolysis

Answer 7

RBC destruction by macrophages primarily in the spleen

-hemolysis occurs intracelllularly normally and is controlled. Does not result in hemoglobinemia of hemoglobinuria
-usually have hyperbilirubinemia and bilirubinuria with pathologic extravascular hemolysis

-icteric and billirubin crystals present

Question 8

Normal heme breakdown

Answer 8

RBC destruction is normal homeostatic process
-aged RBC captured in spleen
-macrophages degrade heme into bilirubin
-bilirubin travels to liver for conjugation
-excreted into bile

Question 9

How does hyperbilirubinemia develop?

Answer 9

1. Hemolytic anemia
   -normal liver, but capacity overwhelmed by increased breakdown of RBC (increased hemoglobin and therefore billirubin in the liver )
2. Liver disease
   -liver can’t handle the normal daily turnover of RBCs

Question 10

Why do you seen icterus?

Answer 10

When you have an increased plasma bilirubin concentration, it will lead to an increase in urinary excretion
**will therefore see bilirubinuria +/- bilirubin crystals prior to clinical icterus

Question 11

What causes hemolytic anemia?

Answer 11

-immune mediated
-infectious agents
-oxidative damage
-mechanical injury
-defects in RBC metabolism
-neoplasia

Question 12

Immune-mediated hemolytic anemia causes

Answer 12

1. Primary auto immune response
2. Secondary to one of: drugs/toxins, infectious agents, neoplasia, transfusion rxn, neonatal isoerythrolysis
3. Unknown! = Idiopathic

Question 13

IMHA pathogenesis- how are the RBCs destroyed?

Answer 13

Production of antibodies which then bind directly or indirectly to RBCs resulting in RBC destruction by one of two methods:

1. Commonly: Antibody-coated RBCs can be engulfed by macrophages = extracellular hemolysis
   resulting in complete breakdown and spherocyte formation

2.Antibody may fix complement= MAC formation leading to intravascular hemolysis and ghost cells

Question 14

Spherocyte formation

Answer 14

Spherocyte formation
-piece of RBC membrane removed
-less surface area, same volume, spherical shape, less central pallor
**difficult to detect except in dogs

Question 15

What is the issue with spherocytes?

Answer 15

Membrane is not flexible, and cannot make it through small gaps of endothelium in spleen
Results in them getting trapped and macrophages will eat them

Question 16

Coombs’ Test

Answer 16

Direct antiglobulin test that confirms the presence of bound antibody or C3 on RBC surface

*many false negatives, not standardized, and therefore often not needed

Question 17

What do you see in a classic IMHA case?

Answer 17

Question 18

Hemotrophic Mycoplasma

Answer 18

An infectious agent cause of hemolytic anemia
-common in cats
-also in dogs, pigs, cattle, llamas, mice
-form pits on RBCs; immune-mediated component

Question 19

Common infectious agents causing hemolytic anemia

Answer 19

1. Hemotrophic Mycoplasma
2. Erythrocytic Anaplasma
3. Babesia (cattle, horses, dogs)
4. Theileria
5. Leptospira, Clostridium, equine infectious anemia virus

Question 20

Oxidative damage causing hemolytic anemia

Answer 20

-Presence of heinz bodies and/or eccentrocyte formation
*also keratocytes and blister cells

Question 21

What causes oxidative damage in dogs?

Answer 21

-garlic
-acetaminophen
-zinc
-skunk spray

Question 22

What causes oxidative damage in cats?

Answer 22

-acetaminophen
-propofol

Question 23

What causes oxidative damage in horses?

Answer 23

-wilted red maple leaves
-garlic

Question 24

What causes oxidative damage in cattle?

Answer 24

-Brassica
-copper
-oak leaves
-acorns

Question 25

Heinz bodies

Answer 25

A small knotted region of denatured hemoglobin
-seen with New methylene blue stain

**-can’t fit through gaps in spleen, macrophages eat them and extravascular hemolysis predominates

Question 26

Eccentrocytes

Answer 26

-fused RBC membranes and hemoglobin content is pushed to side

-can’t fit through gaps in spleen, macrophages eat them and extravascular hemolysis predominates

Question 27

When in heinz bodies normal in cats?

Answer 27

-normal cats
-ill but not anemic cats (diabetes mellitus, hyperthyroidism)
-anemic cats

Question 28

Mechanical injury causing hemolytic anemia

Answer 28

Will see:
-schizocytes, keratocytes (acanthocytes)

Can lead to:
-fibrin strand injury (eg. DIC)
-Turbulent blood flow (eg.endocarditis)
-direct lysis and shortened lifespan due to abnormal shape

Question 29

Acanthocytes

Answer 29

Can be formed by:
-mechanical injury
-splenic, hepatic, renal disorders (likely due to change in membrane lipids)
-most commonly linked with hemangiosarcoma.