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 Anemia – What do you mean it’s not IMHA??? Jason M. Eberhardt DVM, MS, DACVIM.

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Presentation on theme: " Anemia – What do you mean it’s not IMHA??? Jason M. Eberhardt DVM, MS, DACVIM."— Presentation transcript:

1  Anemia – What do you mean it’s not IMHA??? Jason M. Eberhardt DVM, MS, DACVIM

2 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

3 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…”

4 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

5 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

6 Rouleaux or Autoagglutination RouleauxAutoagglutination

7 Before I go any further…  Where do I start…….  Back to basics!!!

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9 The first step… RRemember the Total Protein!!! IIt’s the other half of “blood” IIt’s cheap! IIt’s fast DDO NOT OVERLOOK! AAre just the RBCs being affected or the plasma as well?

10 The next steps…  Morphologic classification  RBC indices  Bone marrow response  Regenerative vs. Non-regenerative  Description of poikilocytosis?  Macrocytic, hypochromic, regenerative anemia with marked spherocytosis

11 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

12 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

13 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.

14 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

15 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

16 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

17 What is consider regenerative???  Normal patient should have <45,000-60,000 absolute retic count  Absolute counts  60, ,000 Early/mild response  150, ,000 Mild-moderate  >250, ,000 Moderate-Marked  Relative %  1-4 % - Mild  5-20 % - Moderate  > 20 % - Marked

18 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.

19 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

20 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???

21 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?

22 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?????

23 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

24 Immune mediated  “Immune-mediated” is a mechanism NOT a disease.  Can be 2 nd to a number of possible causes  Infectious – Babesiosis, Ehrlichiosis, Leishmaniasis, Rickettsioses, Mycoplasma haemofelis, FeLV  Neoplasia  Drugs  Can be initially non-regenerative (esp. in cats)

25 “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

26 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

27 Intravascular hemolysis  Immune mediated  Phosphofructokinase deficiency  Eng. Springers, Amer. Cockers  Babesia infection  Snake envenomation  Heavy metal to toxicity  Zinc  Copper

28 “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

29

30 “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.

31 IHMA???  Started on prednisone, cyclosporine, doxycycline  Needed 2 nd 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

32 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

33 What’s going on???  Horrible IMHA???  Another type of hemolytic anemia?  GI bleeding (from prednisone?, GI mass?)  Diagnostic plan???????????  Explain the decreased total protein

34

35 Non-regenerative anemia  Very common!!!  Usually normocytic normochromic  Microcytic, hypochromic anemias  Usually no poikilocytosis  Huge majority are mild-moderate in severity  2 nd to systemic disease

36 Before going any further…  Is neutropenia and/or thrombocytopenia also present?  What is the duration of clinical signs?  How severe are the clinical signs?

37 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

38 Severe non-regenerative anemia  Toxicity  Estrogen?  Drugs  Renal disease  More than just decreased erythropoietin  Chronic dz, decr. RBC lifespan, ineffective production, blood loss

39 Why can’t it be easy??? BBone marrow exam TTook a long time to develop CCan take even longer to resolve CCan still be very confusing and frustrating

40 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 2 nd to chronic ehrlichiosis  Myelofibrosis – B.M. replaced by fibrous  Myelonecrosis – Drugs, toxins, viral  Neoplasia

41 “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

42 Why cats are not small dogs…  50% of cats with immune mediated disease initially had a non-regenerative response Kohn et al  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

43 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

44 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

45 Summary AAnemia is a common abnormality CCause can often be elusive VVital to approach systematically RRBC indices, bone marrow response, poikilocytosis DDON’T FORGET THE TOTAL PROTEIN!!!

46 QUESTIONS???


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