Hemolytic Anemias and Non-Regenerative Anemias Flashcards
describe immune mediated hemolytic anemia (IMHA)
- antigen-antibody complexes deposited on RBC surface are removed by splenic macrophages
-extravasacular hemolysis - can have intravascular hemolysis
-uncommon as predominant mechanism, complement-mediated (MAC) causes direct lysis
-acutely: ghost cells, hemoglobinuria - antibodies directed against:
-self antigen (primary/idiopathic IMHA)
-foreign antigens but antibody cross reacts with RBC self antigen (drugs, neoplasia)
-RBC parasite
describe primary versus secondary IMHA
- primary:
-can be idiopathic (if rule out all else) or autoimmune
-no underlying cause - secondary: due to
-infectious agents (tick-borne diseases, other systemic infections)
-drugs
-neoplasia
-vaccination
primarily seen in dogs, occasionally other species (cats, horses, cattle)
describe lab findings and tests of IMHA
- expect a strongly regen anemia (esp in dogs)
- look for agglutination (gross and/or microscopic), presence of spherocytes
-lack does NOT rule out IMHA - tests to detect bound antibody or complement complexes on RBC surface (coomb’s test)
-false neg and false positives can occur esp if already treated with immunosuppressants - extravascular hemolysis: hyperbilirubinemia, bilirubinuria
- inflammatory leukogram: hypoxic tissue damage
- thrombocytopenia:
-concurrent immune-mediated thrombocytopenia
-secondary DIC - clinical and laboratory evidence of DIC
NONE of these tests can help distinguish primary from secondary IMHA
describe primary IMHA and also PIMA (split up)
a diagnosis of exclusion of other potential causes!
a special type is PIMA
PIMA: antibodies directed at antigens on erythroid precursor cells
-appears non regenerative peripherally because reticulocytes are not released (either destroyed or not produced because earlier RBCs are destroyed)
-patients can some times have spherocytes and/or positive coomb’s test
-anemia is often moderate to severe, most commonly seen in dogs
-often requires eval of bone marrow sample to diagnose
describe IMHA in cats, horses, and cattle
cats:
-primary/idiopathic: young adult cats (2-6 years)
-secondary: mycoplasma felis, FeLV, FIP, neoplasia, pancreatitis, cholangiohepatitis, UTI
-many cats have non-regen anemia at presentation
horses:
-most commonly secondary due to abx (penicillin, TMS) or infections (clostridium, strep, EIA)
cattle: secondary due to anaplasmosis
describe NIE
neonatal isoerythrolysis, special form of IMHA
- mother becomes sensitized to blood group incompatible erythrocytes and produces antibodies
-pregnancy with fetus with incompatible blood group (most common)
-previous mismatched transfusion - subsequent pregnancy with blood group incompatible fetus may result in NIE once the neonate nurses
-colostrum contains anti-RBC antibodies
-primarily extravascular, but sometimes intravascular hemolysis - most commonly in horse and mule foals with Aa and Qa blood cell antigens or donkey factors
- in cats: B blood group have strong natural anti-A antibodies
- rare in dogs, pigs, cattle
- diagnosis: clinical signs, coomb’s test on neonate
- prevention:
-crossmatch of mare (serum) and stallion (RBCs) in the last few weeks of preg
-withhold colostrum, substitue another mare’s colostrum
describe causes of oxidative damage hemolytic anemia
- plants:
-onions, garlic, chives: from leftovers or baby food with garlic/onion
-brassica: cabbage, kale, rape
-red maple leaves (horses)
-marked IV hemolysis (ghost cells) with hemoglobinuria (dark brown urine, neprhotoxic)
- +/- Heinz bodies and eccentrocytes
-methemoglobinemia
- drugs/chemicals:
-acetaminophen: cats and dogs have limited ability to metabolize in the liver = increased oxidant metabolite formation and hepatic necrosis in dogs
-zinc: pennies, zinc oxide ointment, can also see low numbers of spherocytes
-copper: ruminants (SHEEP) see massive release from liver stores after a stressful event, selenium defiency in cattle
describe signs of oxidative damage
- heinz body formation
-due to denaturation of hemoglobin, extravascular hemolysis, IV hemolysis (ghost cells)
-cats are more susceptible - eccentrocyte formation:
-oxidation and cross-linking of membrane proteins
-decreased deformability = reduced life span - methemoglobin formation
-severe cases, unable to transport oxygen!!
may see all together or separately
describe Heinz bodies
- denatured precipitated hemoglobin attached to the internal surface of the cell membrane
- indicates oxidative damage
- romanowsky-stained smears
-small pale protruding bumps, pale region of cytoplasm - new methylene blue stain will highlight better
describe eccentrocytes
- form when the RBC membrane fuses
- hemoglobin gets pushed to one side, creating a dense dark portion
- fused membranes for a clear skirt
- indicate oxidative damage
describe hypophosphatemia causing hemolytic anemia
- must be severe (<1mg/dl)
- can cause IV hemolytic anemia
- phosphate is critical for ATP production, energy depletion causes RBC lysis
- refeeding syndrome can cause: likely insulin mediaed
- diabetic animals, esp DKA
-loss of P through urine, initiation of insulin treatment shifts P into cells - post parturient hemoglobinuria in dairy cattle
-IV hemolysis within 4 weeks of calving
-hypophosphatemia though to play a role
describe infectious causes of hemolytic anemia
- hemoparasites mostly cause EV, but may have an IV component
-A. marginale in cattle
-M. haemofelis, M. suis
-B. gibsoni (B. canis outside US)
-C> felis
others:
-clostridium, lepto (IV hemolysis)
-equine infectious anemia
-caval syndrome (heartworm): acute IV hemolysis
describe fragmentation anemia
- RBC injury leads to fragmentation
-abnormal vessel (microangiopathy)
-DIC (microthrombi) - can be seen with:
-hemangiosarc
-any cause of DIC
-vasculitis, endocarditis
-burns
-heat stroke
-heartworm infection (caval syndrome) - usually contribute to but do not cause overt anemia
- typical RBC morphology findings: schistocytes, acanthocytes, keratocytes, blister cells
describe non-regenerative anemia
- anemia with no or inadequate bone marrow response
-anemia due to decreased or insufficient RBC production - the most common type of anemia! typically chronic in onset
- additional helpful info:
-history, PE findings
-determine if only RBCs affected or WBCs and platelets too
-chem, UA
-endocrine testing
-bone marrow findings
describe anemia of inflammatory disease (AID)
- most common type of non-regen anemia and anemia in generaly
- secondary to inflammation, infection, neoplasia
-inflammatory cytokines lead to sequestration of iron within macrophages (but not available for erythropoiesis), decreased release of eryrhtopoietin, blunted bone marrow response to Epo, and decreased RBC lifespane - anemia is usually mild
-HCT/PCV just below RI
-sometimes moderate though: PCV 25-30% - normocytic and normochromic
-rarely can become microcytic and/or hypochromic - RBC morphology: often unremarkable, depending on underlying disease
- WBC: can indicate inflammation
-leukocytosis, neutrophilia, left shift, toxic changes - must differentiate from iron defiency anemia!