Regenerative Anemia Flashcards
What is anemia?
reduction in red cell mass resulting in decreased oxygen carrying capacity
What is the normal PCV/Hct in dogs and cats?
DOGS = 37-55%
CATS = 28-45%
What is indicative of regenerative anemia? How is timing important?
increased reticulocytes above the RI —> BM produces and releases the immature RBCs to compensate for demand
reticulocyte formation requires 2-3 days in cats and 3-5 days in dogs - if a blood test is done within this timeframe reticulocytes will be normal/low (pre-regenerative)
How is anemia classified based on morphology?
MCV = size - macrocytic, microcytic, normocytic
MCHC = pallor - hypochromic, normochromic (hyperchromic is considered an artifact)
How is anemia classified by severity in dogs and cats?
DOGS:
- mild = 30-36%
- moderate = 20-29%
- severe = 13-19%
CATS:
- mild = 22-27%
- moderate = 17-21%
- severe = 10-16%
What are the 2 major causes of regenerative anemia?
- blood loss - external (wounds, GIT), internal (tumors or coagulopathies cause bleeding into a body cavity), iatrogenic (recurrent blood draws)
- hemolysis - RBC destruction caused by the immune system, toxins, infections, or neoplasia
bone marrow is working is able to perceive anemia and produce reticulocytes within 3-5 days
What are the 3 major causes of nonregenerative anemia?
- pre-regenerative - bloodwork done within 3-5 days of anemia development without time to produce reticulocytes
- “extra” marrow - iron deficiency, chronic disease, metabolic disease, kidney disease (decreased EPO)
- bone marrow disorders - immune-mediated, infectious, neoplasia, fibrosis, dysplasia
What are the most common clinical signs and physical exam findings associated with anemia?
- pale MM
- tachycardia
- tachypnea
- weakness, lethargy, anorexia, exercise intolerance
- heart murmur due to decreased blood viscosity
severity varies with duration —> acute = critical, chronic = moderate because the patient has been able to adapt to decreases over time
What are the most common findings in patients with anemia caused by hemorrhage?
(decreased platelets or clotting factors)
- petechia, ecchymoses
- hematomas
- melena
- hematemesis
- epistaxis
- hematuria
- hemarthrosis
- abdominal distension
- hypovolemic shock
What are the most common findings in patients with anemia caused by hemolysis?
- icterus - release of bilirubinemia from macrophage destruction of RBCs in the spleen
- splenomegaly
- hemoglobinuria (intravascular), bilirubinuria (extravascular)
What are some causes of blood loss that can lead to anemia?
- trauma
- coagulopathy
- GI hemorrhage
- external parasites
- hematuria (renal) —> idiopathic
- neoplastic rupture/bleeding —> HSA on spleen
What is indicative of intravascular hemolysis that can lead to anemia? What are some causes?
hemolysis within RBC releases hemoglobin into the serum, making it pink
- IMHA
- Babesiosis
- zinc toxicity
- hypophosphatemia
- microangiopathic anemia - red blood cell shearing through abnormally small vessels (HSA)
- inherited erythrocyte abnormalities - pyruvate kinase or phosphofructokinase deficiencies
What is indicative of extravascular hemolysis that can lead to anemia? What are some causes?
icterus - RBCs are filtered by the spleen and broken down by macrophages, releasing bilirubin
- IMHA*
- Mycoplasma hemofelis (infects RBCs)
- Cytauxzoon felis (infects RBCs)
- Heinz body anemia - more mild unless caused by toxins
- Babesiosis
What are 3 foods that can cause Heinz body anemia?
- onions
- garlic
- propylene glycol
What are 6 drugs/chemicals that can cause Heinz body anemia?
- Acetaminophen
- Benzocaine
- Methylene blue
- vitamin K
- DL-methionine
- zinc (pennies minted after 1980s)
What are 3 diseases in cats that can cause Heinz body formation in cats?
- diabetes mellitus
- hepatic lipidosis
- hyperthyroidism
cause Heinz body formation, not anemia
What are some bone marrow causes of non-regenerative anemia?
- immune-mediated —> destruction of precursors
- neoplasia
- infections
- myelodysplasia —> inflammation/neoplasia alters function of BM
- myelofibrosis —> permanent replacement with or increase of collagen in BM = less cells to produce RBCs
What is the most common cause of IMHA? What are some other causes?
PRIMARY = idiopathic
SECONDARY = neoplasia, drugs, infection, vaccination
What is the pathophysiology of IMHA? What are the 2 possible results?
antibodies (IgG, IgM) or circulating immune complexes attach to RBC membrane
- macrophages in the spleen and liver use Fc receptors that attach to the antibodies and destroy the RBCs = hyperbilirubinemia
- complement attaches to Ig, causing intravascular hemolysis = hemoglobinemia
What is the most common cause of hemolytic anemia in dogs? What signalment is most commonly associated?
primary IMHA
- young to middle-aged (6-8 y/o)
- females > males
- Cocker Spaniels
What is the most common cause of feline IMHA? What are they prone to developing? What signalment is associated?
secondary IMHA
pure red cell aplasia, where BM precursors are targeted instead of the mature RBCs in circulation, like in dogs = NON-REGENERATIVE ANEMIA > hemolytic
young males
What onset of signs is most commonly associated with IMHA? What signs are commonly seen?
acute
- anorexia, lethargy*
- tachypnea, tachycardia
- weakness, collapse
- pale MM, icterus
- heart murmur
- splenomegaly
What is the most common type of anemia found on bloodwork in cases of IMHA? What are 2 exceptions?
- severe
- regenerative (reticulocytosis)
- polychromasia
NON-REGENERATIVE when there is:
- anemia of brief duration
- antibodies directed against RBC precursors in the BM
What are 3 other laboratory findings other than anemia seen with IMHA? What is most commonly seen in dogs only?
- autoagglutination due to the presence of antibodies on membranes - dilute blood with saline to prevent nonspecific agglutination or Rouleaux
- leukocytosis +/- left shift
- thrombocytopenia - immune-mediated thrombocytopenia, DIC, consumption
spherocyte formation
What are the 2 most common biochemical findings seen with IMHA?
- hyperbilirubinemia
- elevated liver enzymes, most commonly ALT - caused by increased BILI metabolism, hepatic damage caused by hypoxia, or DIC
What are the 3 major differential diagnoses for IMHA?
- infectious disease - Rickettsia, Babesia, Mycoplasma, Cytaxuzoon
- neoplasia - lymphoma paraneoplastic syndrome, malignant histiocytosis lyses RBCs
- toxins/drugs - zinc (pennies minted after 1982), onions, garlic
What is necessary to diagnose IMHA?
regenerative anemia with evidence of hemolysis and one or more of the following:
- spherocytosis - smaller, rounder, darker RBCs
- autoagglutination
- positive Coombs test - RBCs + Ab detected
Diagnosing IMHA:
What are the 3 most common causes of secondary IMHA?
- infectious - Rickettsia, Babesia, Mycoplasma, Cytaxuzoon
- neoplastic -lymphoma, malignant histiocytosis
- drugs - Cephalosporins, Sulfas
diagnostics is dependent on individual case findings and compliance
- rads and U/S recommended to rule out/in neoplasia
- 4DX Snap for HW, Anaplasma, Lyme, Ehrlichia
- PCR and serology for Babesia, Mycoplasma, and other tick-borne diseases
What are the 3 major complications associated with IMHA?
- concurrent immune-mediated thrombocytopenia (Evan’s syndrome)
- DIC
- thromboembolism in lungs, liver, or spleen - fatal hypercoagulable state
What are the 5 major aspects to treating IMHA?
- immune suppression
- IVIg adjuvant to block Fc receptors on macrophages and keep them from binding to and destroying RBCs
- antithrombotics to avoid PTE
- blood transfusions
- SECONDARY = remove offending drugs, treat neoplasia/tick-borne disease
What immunosuppressive is recommended for IMHA? What are 5 second-line options?
Prednisone at immunosuppressive dose (2 mg/kg/day capped at 60 mg/dog) —> larger doses in large dogs are associated with increased clinical signs
- Cyclosporine
- Mycophenolate
- Leflunomide
- Azathioprine
- Chlorambucil (cats)
Why do practitioners commonly use two immunosuppressives when treating IMHA?
- additional drugs are helpful if Prednisone is not working or is waiting to kick in
- Prednisone side effects can be limited by using an additional medication —> quick results = earlier tapering of Pred (steroid-sparing effect)
- already behind in the game at the time of diagnosis
What antithrombotics are recommended for cases of IMHA? Why?
- Clopidogrel
- low-dose Aspirin
- no findings of one having better effects compared to the other
prevents PTE, the major cause of mortality in IMHA patients
When are blood transfusions recommended in patients with IMHA? What are the 3 options?
when patients are clinical
- pRBCs - 1 mL/kg to increase PCV by 1%
- fresh whole blood (donor on site) - 2 mL/kg to increase PCV by 1%
- stored whole blood - 2 mL/kg to increase PCV by 1%
If a patient’s hematocrit is at 15% and is is desired to increase it to 25% with a pRBC transfusion, what amount is recommended?
pRBCs = 1 mL/kg to increase by 1%
10 mg/kg —> typically given over 4 hours, since blood can quickly become contaminated at room temperature
