Hemolytic Anemia Flashcards
What is hemolytic anemia?
When RBCs are destroyed
What basic components indicate blood loss or hemolytic anemia?
- regenerative anemia
- macrocytic, hypochromic
- polychromasia/reticulocytosis
What extra things indicate hemolytic anemia rather than blood loss?
- Hemogloinemia/hemoglobinuria
- hyperbilirubinemia/bilirubinuria
- Abnormal RBC morphology or parasites
- Proteins within normal range because they are not being lost from the vasculature
Intravascular vs extravascular hemolysis
Can be used to determine etiology of anemia
-intravascular generally poorer prognosis
-extravascular more common
*although both can be present
What is intravascular hemolysis?
RBC destruction within blood vessels
-causes hemoglobinemia and hemoglobinuria (increased MCH and MCHC)
-may see hyperbilirubinemia and bilirubinuria over time
Why is the free hemoglobin from RBC destruction (intravascular hemolysis) bad?
- Hemoglobinuric nephropathy (kidneys filtering hemoglobin)
- Thrombosis
Extravascular hemolysis
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
Normal heme breakdown
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
How does hyperbilirubinemia develop?
- Hemolytic anemia
-normal liver, but capacity overwhelmed by increased breakdown of RBC (increased hemoglobin and therefore billirubin in the liver ) - Liver disease
-liver can’t handle the normal daily turnover of RBCs
Why do you seen icterus?
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
What causes hemolytic anemia?
-immune mediated
-infectious agents
-oxidative damage
-mechanical injury
-defects in RBC metabolism
-neoplasia
Immune-mediated hemolytic anemia causes
- Primary auto immune response
- Secondary to one of: drugs/toxins, infectious agents, neoplasia, transfusion rxn, neonatal isoerythrolysis
- Unknown! = Idiopathic
IMHA pathogenesis- how are the RBCs destroyed?
Production of antibodies which then bind directly or indirectly to RBCs resulting in RBC destruction by one of two methods:
- 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
Spherocyte formation
Spherocyte formation
-piece of RBC membrane removed
-less surface area, same volume, spherical shape, less central pallor
**difficult to detect except in dogs
What is the issue with spherocytes?
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
Coombs’ Test
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
What do you see in a classic IMHA case?
Hemotrophic Mycoplasma
An infectious agent cause of hemolytic anemia
-common in cats
-also in dogs, pigs, cattle, llamas, mice
-form pits on RBCs; immune-mediated component
Common infectious agents causing hemolytic anemia
- Hemotrophic Mycoplasma
- Erythrocytic Anaplasma
- Babesia (cattle, horses, dogs)
- Theileria
- Leptospira, Clostridium, equine infectious anemia virus
Oxidative damage causing hemolytic anemia
-Presence of heinz bodies and/or eccentrocyte formation
*also keratocytes and blister cells
What causes oxidative damage in dogs?
-garlic
-acetaminophen
-zinc
-skunk spray
What causes oxidative damage in cats?
-acetaminophen
-propofol
What causes oxidative damage in horses?
-wilted red maple leaves
-garlic
What causes oxidative damage in cattle?
-Brassica
-copper
-oak leaves
-acorns
Heinz bodies
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
Eccentrocytes
-fused RBC membranes and hemoglobin content is pushed to side
-can’t fit through gaps in spleen, macrophages eat them and extravascular hemolysis predominates
When in heinz bodies normal in cats?
-normal cats
-ill but not anemic cats (diabetes mellitus, hyperthyroidism)
-anemic cats
Mechanical injury causing hemolytic anemia
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
Acanthocytes
Can be formed by:
-mechanical injury
-splenic, hepatic, renal disorders (likely due to change in membrane lipids)
-most commonly linked with hemangiosarcoma.
