Presentation on theme: " Anemia – What do you mean it’s not IMHA??? Jason M. Eberhardt DVM, MS, DACVIM."— Presentation transcript:
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 RouleauxAutoagglutination
Before I go any further… Where do I start……. Back to basics!!!
The first step… RRemember the Total Protein!!! IIt’s the other half of “blood” IIt’s cheap! IIt’s fast DDO NOT OVERLOOK! AAre 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 Early/mild response 150, ,000 Mild-moderate >250, ,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 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)
“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 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
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 2 nd 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??? BBone marrow exam TTook a long time to develop CCan take even longer to resolve CCan 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 2 nd 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 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 AAnemia is a common abnormality CCause can often be elusive VVital to approach systematically RRBC indices, bone marrow response, poikilocytosis DDON’T FORGET THE TOTAL PROTEIN!!!