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