4 – RBC 2 Flashcards
When do you know you have a hemolytic anemia?
- Regenerative
- Macrocytic, hypochromic
- Polychromasia/reticulocytosis
- *hemoglobinemia/hemoglobinuria
- *hyperbilirubinemia/bilirubinuria
- *abnormal RBC morphology or parasites
- Proteins WRI
Intravascular vs. extravascular hemolysis
- May help determine etiology
- Intravascular=poor prognosis
- Extravascular=more common
- *often both are present
Intravascular hemolysis
- RBC destruction within blood vessels
- Hemoglobinemia and hemoglobinuria
o Increased MCH and MCHC(measuring free Hb and intact Hb in RBCs) - Over time: hyperbilirubinemia and bilirubinuria
- **free Hb is bad=poor prognosis
o Hemoglobinuric nephropathy and thrombosis
Extravascular hemolysis
- RBC destruction by macrophages primarily in spleen
- intracellular=normal process
- does NOT cause hemoglobinemia or hemoglobinuria
- usually have hyperbilirubinemia and bilirubinuria with pathologic extravascular hemolysis
Icterus in the big picture
- RBC destruction is a normal homeostatic process
- Aged RBC captured in spleen
- Macrophages degrade heme into bilirubin
- Bilirubin travels to liver for conjugation
- Excreted into bile
What are the 2 ways that hyperbilirubinemia can develop?
- Hemolytic anemia
a. Normal liver, but capacity overwhelmed by increased breakdown of RBC - Liver disease
a. Liver can’t handle normal daily turnover of RBCs
What is and what happens with pathologic hemolysis?
- *accelerated RBC destruction
- Intravascular or extravascular
- Increased Hgb breakdown in macrophages=increased delivery of bilirubin to liver
- *if liver can handle=wont see hyperbilirubinemia
What happens when there is an increased plasma [bilirubin]?
- Increased urinary excretion
o Bilirubinuria +/- bilirubin crystals
o Bilirubinuria precedes clinical icterus (low renal threshold)
What are the many paths to destruction?
- Immune-mediated
- Infectious agents
- Oxidative damage
- Mechanical injury
- (Defects in RBC metabolism)
- (neoplasia)
What is the biggest cause of hemolytic anemia in dogs?
- Immune-mediated
IMHA due to
- Primary: auto-immune
- Secondary
o Drugs/toxins
o Infectious agents
o Neoplasia
o Transfusion reaction
o Neonatal isoerythrolysis - *initiating cause often undetermined (idiopathic)
Production of Ab with IMHA
- Direct or indirect binding to RBC
- Result in RBC destruction
What are the 2 ways RBC may be destroyed in IMHA?
- Ab-coated RBC engulfed by macrophages
o Extravascular
o Spherocyte formation - Ab may fix complement=MAC formation
o Intravascular hemolysis
o Ghost cells - *extravascular hemolysis predominates
Spherocyte formation with RBC destruction
- Piece of RBC membrane removed
- Less SA, same volume
- Spherical shape
- Loss of central pallor
- *Difficult to detect except in dogs
What is the problem with spherocytes?
- NOT flexible
- Trapped in spleen and macrophages will come along and ‘eat them’
Ab may fix complement with RBC destruction
- Get a hole in membrane of RBC=all Hb leaks into circulation
Coomb’s Test (direct antiglobulin test: DAT)
- Confirm presence of bound Ab or C3 on RBC surface
- *many false negatives
- Not standardized
- Often not needed
What is seen in a classic case of IMHA?
- Regenerative anemia
- Spherocytes
- Coomb’s +
- Hyperbilirubinemia/bilirubinuria
- Inflammatory leukogram
- Might see
o Agglutination
o Ghost cells: intravascular
o Thrombocytopenia: if concurrent IM destruction of platelets
Infectious agents: what is one of the only things you will see in Canada
- Hemotrophic Mycoplasma
o Epicellular: on surface of RBC
o Form invaginations - *cats, dogs, pigs, cattle, llamas, mice
- Immune-mediated component to hemolysis
What are some other examples of infectious agents?
- Erythrocytic Anaplasma
- Babesia: cattle, horses, dogs
- Theileria
- Leptospira, Clostridium, EIA virus
What does oxidative damage result in?
- Heinz body and/or eccentrocyte formation
o May see keratocytes and blister cells - *onions in all species (except humans)
What can cause oxidative damage in dogs?
- Garlic
- Acetaminophen
- Zinc
- Skunk spray
What can cause oxidative damage in cats?
- *acetaminophen
- Propofol
What can cause oxidative damage in horses?
- Wilted red maple leaves
- Garlic
What can cause oxidative damage in cattle?
- Brassica
- Copper
- Oak leaves
- Acorns
What are Heinz bodies?
- Denatured Hg
- See on New Methylene blue stain
What are eccentrocytes?
- Fused RBC membranes
- All Hg content to one side
What are the problems with Heinz bodies and eccentrocytes?
- Can’t get through spleen
o Eaten by macrophages
o *extravascular hemolysis predominates - May have small component of intravascular hemolysis
Cats are special: small, individual Heinz bodies can be seen in
- Normal cats
- Ill but not anemic
o Diabetes mellitus
o Hyperthyroidism - Anemic cats
What is seen with mechanical injury? What can lead to it?
- Schizocytes, keratocytes (maybe acanthocytes)
- *direct lysis and shortened lifespan due to abnormal shape (trapped in spleen)
- Due to:
o Fibrin strand injury (ex. DIC)
o Turbulent blood flow (ex. endocarditis)
Acanthocytes: significance
- **hemangiosarcoma
- Splenic, hepatic, renal disorders
o Due to change in membrane lipids - Mechanical injury
o Seen with schizo/kerato - *irregularly irregular
What are the 3 possibilities if you get 3+ for blood on a urinalysis?
- Intact erythrocytes
- Myoglobin
- Hemoglobin
- *if cystocentesis=likely where the RBC are coming from