Anemia * It*s not IMHA??? - VetCare Internal Medicine

Anemia – What do you
mean it’s not IMHA???
Jason M. Eberhardt DVM, MS, DACVIM
S One of the most common CBC abnormalities
S 10-30% of patients
S Why is it still so confusing?
S Back to basics
S Systematic approach to anemia
S Avoiding common pitfalls
Some thoughts…
S “You need to have the correct diagnosis before you can
recommend the correct treatment.”
S “If you always have the correct diagnosis then you’re not a
really veterinarian…you’re probably a breeder.”
S “You need to run a minimum of 5 diagnostic tests prior to
starting steroids…”
S Mean Corpuscular Volume (MCV) – Avg. RBC size
S Macrocytosis
S Microcytosis
S Normocytic
S Mean corpuscular Hgb concentration (MCHC) – [ ] of Hgb vol. RBC
S Hypochromic
S Normochromic
S Macrochromic
S Reticulocytes – Immature RBCs released from B.M. early
S Normoblasts/metarubricytes – nucleated erythrocytes
Definitions continued…
S Poikilocytosis – Variation of RBC shape
S Rouleaux – Stacks of coins
S Small amount is normal
S Increased fibrinogen or acute phase proteins
Typically seen in inflammatory conditions
S Autoagglutination – Aggregate in grapelike clusters
S Must be differentiated from rouleaux
S Rouleaux disperses when blood is mixed with saline
Rouleaux or Autoagglutination
Before I go any further…
S Where do I start…….
S Back to basics!!!
The first step…
S Remember the Total Protein!!!
S It’s the other half of “blood”
S It’s cheap!
S It’s fast
S Are just the RBCs being affected or the plasma as well?
The next steps…
S Morphologic classification
S RBC indices
S Bone marrow response
S Regenerative vs. Non-regenerative
S Description of poikilocytosis?
S Macrocytic, hypochromic, regenerative anemia with marked
Morphological classification
S Usage of RBC indices (MCV/MCHC) to “describe” the
S Remember MCV/MCHC are MEAN calculations
S Large # of RBCs affected prior to increases/decreases
S Allows characterization of anemia into a category
S Helps with ranking differential diagnoses
S Are found on nearly all in-house CBC units
Normocytic normochromic
S Most common
S “Normal” RBCs
S Most commonly denotes a non-regenerative anemia
S Usually lacks RBC morphology changes
S “Pre-regenerative”
S First 1-3 days of acute loss/lysis
Macrocytic hypochromic
S Usually indicates a regenerative anemia
S Reticulocytes are relatively larger then mature RBCs
S Hypochromic because Hgb synthesis is not complete
S Only 8% of 6752 patients with reg. anemia had both
increased MCV & decreased MCHC DiNicola et al.
Macrocytic normochromic
S Usually misclassification due to insensitivity of MCV/MCHC
S Autoagglutination?
S Feline Leukemia
S Poodles – Congenital dyserythropoiesis
S Not anemic
S Large problem in humans
S B12 &/or folate deficiency
Role in veterinary medicine is questionable
Microcytic hypochromic
S Consistent with an iron deficiency anemia
S Inadequate amount of Hgb is produced
S Typically seen in chronic conditions
S GI blood loss
S Severe parasitism
S PSS & Hepatic atrophy
S Myelodysplastic syndromes
S Congenital: Akitas, Shiba Inu, Chow breeds
S Not typically hypochromic
Bone marrow response
S Is there a regenerative response?
S Evaluation of reticulocytosis
S No reticulocytosis/polychromasia expected during first 1-3
days (maybe not at all if anemia stays mild)
S Response peaks 4-5 days (with normal B.M.)
S Erythrocyte indices start to change 7-14 days
What is consider regenerative???
S Normal patient should have <45,000-60,000 absolute retic count
S Absolute counts
S 60,000-150,000 Early/mild response
S 150,000-250,000 Mild-moderate
S >250,000-500,000 Moderate-Marked
S Relative %
S 1-4 % - Mild
S 5-20 % - Moderate
S > 20 % - Marked
Regenerative anemia
S Loss vs. Lysis
S External blood loss
Low to low-normal T.P.
S Hemolytic disease
S High to high-normal T.P.
Acute external blood loss
S PCV does not fully reflect severity first 1-3 days
S Reticulocytosis should start by day 3
S Peak reticulocytes day 4-7
S PCV increases to low normal w/in 2 wks
S May take up to 4-5 weeks to return to normal
S Mild anemia does not stimulate strong erythropoietin release
Chronic blood loss
S Iron deficiency and negative protein balance develops after
“several” weeks in adults
S Occurs more rapidly in young animals (low iron stores)
S Initially non/”pre” regenerative
S Period of regenerative anemia depending on severity
S Eventually returns to being poorly/non-regenerative
S Often have thrombocytosis
S Remember RBC indices do not change for 7-14 days
S Getting blood transfusions???
Hemolytic anemia
S Hemolysis is a mechanism NOT a “disease”
S Lots of “non” immune mediated causes
Low serum phosphorus
S Normal to increased T.P.
S Spherocytosis and/or autoagglutination
S Over interpretation is common
S Can be seen in diseases that are not “primary”
S Positive Coomb’s Test?
Direct Coomb’s Test
S Identifies presence antibodies/compliment on RBCs
S They may/may not actually be directed towards RBCs
S This may/may not actually cause damage to RBCs
S Neither highly specific or sensitive for IMHA
S Positive in 60-70% of cases
S Positive results – should have other evidence of IMHA
S Effect of steroids?
S **NOTE** – What is the end point of the test?????
Breaking it down…
S Try to subclassify into intravascular vs. extravascular
S Alters differential diagnosis
S Intravascular – Rapid breakdown in vascular system
Pink urine, pink serum
Hemoglobinuria best indicator
Hyperbilirubinemia typically more profound then in extravascular
S Extravascular – removal of RBCs by spleen, liver, B.M.
More common
Often has icterus, splenomegaly, hepatomegaly
Immune mediated
S “Immune-mediated” is a mechanism NOT a disease.
S Can be 2nd to a number of possible causes
S Infectious – Babesiosis, Ehrlichiosis, Leishmaniasis,
Rickettsioses, Mycoplasma haemofelis, FeLV
S Neoplasia
S Drugs
S Can be initially non-regenerative (esp. in cats)
“Penny” 6 year FS Cocker
S Presented for severe lethargy, “yellow skin” and “peeing blood”
S Severe, macrocytic, normochromic strongly regenerative anemia
with mild-moderate spherocytosis
S Slide agglutination negative
S High total protein
S Abdominal ultrasound WNL
S Infectious disease titers all negative
The “Penny” dilemma
S Needed multiple transfusion in a 5-6 day period
S Continued to have hemolysis despite aggressive
immunosuppressive therapy
S Where do we go from here???
S “Peeing” blood – hemoglobinuria
S Intravascular hemolysis
Intravascular hemolysis
S Immune mediated
S Phosphofructokinase deficiency
S Eng. Springers, Amer. Cockers
S Babesia infection
S Snake envenomation
S Heavy metal to toxicity
S Zinc
S Copper
“Penny” 6 yr FS Cocker Spaniel
S Presented for severe lethargy, yellow skin and “peeing
S Severe, macrocytic, normochromic strongly regenerative
anemia with mild-moderate spherocytes
S Abdominal ultrasound WNL
S Infectious disease titers all negative
“Sheldon” 9 yr MC Jack Russell
S Presented with clinical evidence of anemia
S Severe leukocytosis (54,000), severe anemia (9%), high
normal platelets, mild-moderate reticulocytosis
S Total Protein – 4.9 g/dL
S VF, Ehr. Neg.
S Started on prednisone, cyclosporine, doxycycline
S Needed 2nd transfusion 1 week later
Added azathioprine
S PCV still low 2 weeks later
S Chest rads and abd. u/s WNL
S Increased prednisone, continued on cyclosporine and azathioprine
S 3rd transfusion in 4 weeks
S Added leflunomide
S Repeat abdominal ultrasound WNL
More anemia!!!
S Initial PCV/TP at EAC
S 12%/4.8
S Reference lab work
S Hypoalbuminemia (2.6 g/dL), globulin WNL (1.7 g/dL),
BUN increased (mild), Total bilirubin (mild)
S Inflammatory leukogram
S Severe reticulocytosis
What’s going on???
S Horrible IMHA???
S Another type of hemolytic anemia?
S GI bleeding (from prednisone?, GI mass?)
S Diagnostic plan???????????
S Explain the decreased total protein
Non-regenerative anemia
S Very common!!!
S Usually normocytic normochromic
Microcytic, hypochromic anemias
S Usually no poikilocytosis
S Huge majority are mild-moderate in severity
S 2nd to systemic disease
Before going any further…
S Is neutropenia and/or thrombocytopenia also present?
S What is the duration of clinical signs?
S How severe are the clinical signs?
I need more RBCs…
S Mild-moderate NR anemia
S Search for an underlying disease first
S Anemia of chronic/inflammatory disease
S Neoplasia, renal disease, hepatic disease, infectious,
inflammatory, endocrine
S Drugs
Severe non-regenerative anemia
S Toxicity
S Estrogen?
S Drugs
S Renal disease
S More than just decreased erythropoietin
S Chronic dz, decr. RBC lifespan, ineffective production, blood
Why can’t it be easy???
S Bone marrow exam
S Took a long time to develop
S Can take even longer to resolve
S Can still be very confusing
and frustrating
Bone Marrow disease
S Immune mediated
S Maturation arrest vs. Pure Red Cell Aplasia
S Myelophthisic syndromes - multiple cell lines often affected
S Aplastic anemia – B.M. replaced by fat
Can be 2nd to chronic ehrlichiosis
S Myelofibrosis – B.M. replaced by fibrous
S Myelonecrosis – Drugs, toxins, viral
S Neoplasia
“Howard” 9 yr MN DSH
S Progressive lethargy, wt. loss for several weeks
S Marked (12%), macrocytic, normochromic anemia
S Total protein 6.2 g/dL
S Absolute reticulocyte count 40,000
Retic. total 2%
Corrected 0.65%
S FelV/FIV negative
S Chest radiographs, abdominal ultrasound WNL
Why cats are not small dogs…
S 50% of cats with immune mediated disease initially had a
non-regenerative response Kohn et al. 2006
S 2/3 were <3 years (range was 1-9 yr)
Bone marrow disease – 53%
Infectious – 22%
Hemolysis – 11%
Immune Mediated – 6%
S Severity of anemia associated with B.M. disease
Korman et al. 2013
Bone marrow or bust
S Owner noticed gradual decline
S More consistent with non-regenerative disease
S Transfusion
S Recheck 2-3 days later vs. bone marrow now
S Marked erythroid hypoplasia/aplasia
S Immune mediated vs. FelV
S Bone marrow IFA positive for FelV Stutzer et al. 2010
RBC shape descriptions
S Many have little/no clinical significance
Anisocytosis, elliptocytes, codocytes, leptocytes, *echinocytes*
S Spherocytes – Evidence of hemolysis
S Acanthocytes - Hemangiosarcoma, hepatic dz
S Schistocytes - DIC, Fe def, CHF, myelofibrosis,
hemangiosarcoma, other neoplasia
S Anemia is a common abnormality
S Cause can often be elusive
S Vital to approach systematically
S RBC indices, bone marrow response,

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