Regenerative Anemia - All 3 parts Flashcards
“Regenerative Anemia”
implies there is an appropriate bone marrow response with increased erythropoiesis and RBC release
Blood Loss Anemia:
Acute:
External
External hemorrage - protein and iron are lost
skin lacerations, nose, genitourinary tract, GI tract,
Parasitism
Removal of blood for transfusion
Blood Loss Anemia:
Acute:
Internal
Internal hemorrhage - protein and iron recycled
Into a body cavity or deep tissues
Some red cells can be reabsorbed and re-enter the circulation
Phagocytosis of red cells by tissue macrophages may increase serum billirubin
Blood Loss Anemia
blood loss → hypovolemia → hemodilution → anemia
Hyperbiliruninemia
The cause of icterus
- Prehepatic:
- increased Bu production → hemolytic disorders
- Hepatic:
- decreased Bu uptake (fasting, decreased functional mass)
- Decreased Bu conjugation
- Functional cholestasis (sepsis-associated)
- Intrahepatic cholestasis
- PostHepatic
- Posthepatic obstructive cholestasis
Hyperbilirubinemia:
Prehepatic
Increased bilirubin production
- Hemolytic disease
- increased Bu production
- Anemia, bilirubinuria, +/- hemoglobinemia/hemogloniuria
- Bilirubin processed by liver as in health but at an accelerated rate
- Increased amounts of unconjugated bilirubin overwhelms the capacity of hepatocyte membrane carriers of the hepatocyte itself
Mechanisms of destruction:
Extravascular hemolysis
more common
RBCs are removed from circulation by macrophages
splenic clearance predominant
Presence of spherocytes is common
Mechanisms of destruction:
Intravascular hemolysis
- RBCs rupture in circulation and release hemoglobin
- Hemoglobin makes plasma pink/red
- Hemogloinemia
- Hemoglobin may enter the urine causing it to be red
- hemoglobinuria
- “ghost cells” may be seen on a blood smear
Pathogenesis of Immune Hemolysis
- RBCs coated with ESAIg undergo extravascular hemolysis in macrophages
- RBCs coated with ESAIg are converted to spherocytes by macrophages removing the RBC membrane
- Spherocytes undergo either extravascular or intravascular hemolysis becuase of their rigidity and fragility respectively
- Some ESAIg may bind complement which activates the complement cascade leading ot intravascular hemolysis via the membrane attack complex
ESAIg = Erythrocytes Surface-Associated Immunoglobulin
Overview of IMHA laboratory findings
- Always
- decreased Hct, RBC, and Hgb
- Almost Always:
- positive for RBC surface associated immunoglobin
- Evidence of regeneration
- Inflammatory leukogram
- Case Dependent:
- hemoglobinemia, hemoglobinuria
- Hyperbilirubinemia and bilirubinuria
- Spherocytes on the blood film
- Agglutination
- Coomb’s test positive - tests for presence of antibody or complement on RBC
- Chemistry abnormalities will be discussed later
Coombs’ test (Direct antiglobulin test)
- Detects antibody or complement bound to the RBC surface
- RBCs are washed with saline to remove unbound proteins, and then incubated with species specific anti-IgG, anti-IgM and anti-complement
- Coombs reagent binds Ab or complement that is already bound to the RBCs
- A positive result is indicated by RBC afflutination or Hemolysis if complement is added
- False negatives are common
IMHA - exceptions
- Rarely anemia may be nonregenerative on presentation
- short duration <2-3 days
- marrow precursors are also a target for destruction
- Other concurrent disease interferes with erythropoiesis
- Spherocytes are usually seen but NOT ALWAYS seen
- if rapidly removed from circulation they may not accumulate in blood
- In suspected cases without spherocytes recommend RBC surface associated immunoglobulin assay
Hemolytic anemia due to Oxidative Damage
-
Allium species
- onions, leeks, garlic, chives
-
Acetominphen
- Cats
- Brassica
- cabbage, kale, rape
- Benzocaine
- Phenylhydrazine
- Methylene Blue
- Vitamin K / Vitamin K antagonism intoxication
-
Zinc
- dogs that eat pennies
- Naphthalene
- Inflammation
- Neoplasia
- Diabetes Mellitus, and Hyperthryroidism
-
Wilted red maple leaves
- horses, ponies, llamas, Zebras
- Propylene Glycol
- Copper
- Crude Oil
Organisms that cause Hemolytic Anemia:
Mycoplasma haemofelis
- Results in IMHA
- Agglutination may be present
- Transmission not well understood
- fleas and ticks
- Cat bites
- Latrogenic Exposure
- Queen of fetus
- Present throughout the world
- Latent carriers
- Stress may initiate recurrence of clinical disease
-
Opportunistic Organism
- usually causing disease only in splenectomized or severly immunosuppressed dogs
- Splenectomized dogs develop active infections if they are transfused with infected blood, or it they have latent infections
- Active infections may manifest days to weeks after splenectomy
Hemoplasmas of Ruminants
Mycoplasma Wenyonii
occurs worldwide and similar to M. heamocanis in dogs
Usually only causes severe anemia in immunosuppressed or splenectomized cattle
Mycoplasma heamosuis
pathogenic in very young pigs, as well as pigs that have been splenectomized, causing severe hemolytic anemia and sometimes death
In older animals, infection is associated with poor weight gain.
Anaplasma marginale
- Intracellular, but appear to project from the cell
- Organisms most numerous in acute disease
- 4-5 days later, typically difficult to find organisms
- Resulting anemia is immune-mediated
- Moderate to severe anemia, polychromasia, reticulocytosis on NMB, basophilic stippling, mild to marked hyperbilirubinemia +/- bilirubinuria
- PCT postive for A. marginale
Babesia / Theileria
- Dogs; Babesia canis and B. gibsoni
- Cattle: B. bovis, and B. bigemina
- Horses: Theileria equi, B. cabali
- Sheep. B. ovis, and B. motasi
- Cats: B. cati, B. felis, B. herpailuri, B. pantherae
- Transmission:
- protozoal tick-born disease
- Transplacental transmission and iatrogenic
- Vary in appearance; both large forms and small forms have been described
Mechanical Fragmentation:
RBC Fragmentation
- Schistocytes - fragmented RBCs
- anemia may be mild, moderate or severe depending on the underlying disease
- Regenerative or nonregenerative
- Traumatic fragmentation of RBCs is caused by fibrin strands forming in small vessels of severly turbulent blood flow
- Microangiopathic disease
- DIC, heartworm dz, Hemangiosarcoma, vasculitis
Hypophosphatemia induced hemolysis
usually less than 1 mg/dl
Erythrocyte glycolysis is inhibited
leading to decreased erythrocyte ATP concentrations, and subsequent hemolysis
Postparturient Hemoglobinuria in cattle
- Syndrom of high producing dairy cows
- intravascular hemolysis, anemia, and hemoglobinuria
- Usually occurs within 4 weeks of calving
- Most, but not all, cows with this syndrom are hypophophatemic at the time of anemia
- Theory:
- previous hypophophatemia predisposes erythrocytes to injury and oxidative damage, primarily by decreasing ATP and Glutathione
Hypophosphatemia in diabetic cats
phosphorus loss in the urine of polyuric animals
Several instances of hypophosphatemia-induced hemolysis have been reported in cats
Anemia due to Histiocytic Neoplasia
- Hemophagocytic histiocytic sarcoma
- neoplastic macrophages
- All breed affected, but overrepresented breeds include:
- bernese mountain dogs
- golden retrievers
- rottweilers
- Labrador
- Aggressive clinical course with poor prognosis
- splenomegaly
- regenerative anemia
- Bi or pancytopenias are typical
Water intoxication induced hemolysis
seen most commonly in calves
- Hemolysis, hemoglobinuria, pulmonary edema, brain edema, convulsions, coma, and death
- may occur in calves that have unlimited access to water following its unavailability
- Water intoxication may cause death within 2 hours, but most calves survive with no permanent ill effects
- cause of hemolysis is decreased osmolarity of plasma
- Red cells are in a hypotonic environment resulting in fluid uptake by the cells
- Occurs in calves form 4-5 months of age becasue osmotic fragility of thier erythrocytes is greatest at this time.
Hemolytic anemia caused by bacteria:
Clostridium perfringens Type A
- “Yellow Lamb Disease” or “enterotoxemic jaundice” in lambs and calves
- IMHA in horses
- Bacteria produces a phospholipase, which hydrolyses cell membrane phospholipids of erythrocytes, as well as those of other cells
- Lethargy, fever, pale mucous membranes, anemia, hemoglobinuria, and icterus
Hemolytic anemia caused by bacteria:
Clostridium haemolyticum and C. novyi Type D
- “Bacillary hemoglobinuria” or “red water disease” in cattle which is fatal
- Bacterial spores in macrophages of the liver. Liver fluke migration results in growth of the bacteria and production of toxic enzymes that metabolize lipids and protein in cell walls
- Endemic in swampy areas of numerous countries, including the US
- Rarely recognized ante-mortem
Hemolytic anemia caused by bacteria:
Leptospirosis
- Hemolytic disease in young calves and lambs
- rarely hemolytic anemia in dogs
- Toxins produced by the bacteria may act as hemolysins
- Probable immune mediated component
