Presentation on theme: "Anemia – What do you mean it’s not IMHA???"— 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 Back to basics 10-30% of patientsWhy is it still so confusing?Back to basicsSystematic approach to anemiaAvoiding 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 MacrocytosisMicrocytosisNormocyticMean corpuscular Hgb concentration (MCHC) – [ ] of Hgb vol. RBCHypochromicNormochromicMacrochromicReticulocytes – Immature RBCs released from B.M. earlyNormoblasts/metarubricytes – nucleated erythrocytesReduction in # of circulating RBCs, HCT and HBErythrocyte indices – remember they are MEAN calculations – a large # of cells have to be abnorm. To pull value out of ref. range – IMHA only 8.3 % are actually hypochromic on blood workMacrochromic – almost all lab errors (due to heinz bodies or hemolysis or severe lipemia– people sickle cell anemia, hereditary spherocytosisMCH – mean corpuscular hemoglobin Hgb x 10/PCV
5 Definitions continued… Poikilocytosis – Variation of RBC shapeRouleaux – Stacks of coinsSmall amount is normalIncreased fibrinogen or acute phase proteinsTypically seen in inflammatory conditionsAutoagglutination – Aggregate in grapelike clustersMust be differentiated from rouleauxRouleaux disperses when blood is mixed with salineSpherocytes (RBCs lack central pallor near feather edge), Echinocytes, Acanthocytes (HAS, hepatic dz), Schistocytes (DIC, Fe def, CHF, myelofibrosis, HAS, malig. Histo)
9 The first step… Remember the Total Protein!!! DO NOT OVERLOOK! It’s the other half of “blood”It’s cheap!It’s fastDO NOT OVERLOOK!Are just the RBCs being affected or the plasma as well?
10 The next steps… Morphologic classification Bone marrow response RBC indicesBone marrow responseRegenerative vs. Non-regenerativeDescription 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 calculationsLarge # of RBCs affected prior to increases/decreasesAllows characterization of anemia into a categoryHelps with ranking differential diagnosesAre found on nearly all in-house CBC unitsNormocytic, normochromic, Macrocytic hypochromic, Microcytic hypochromic
12 Normocytic normochromic Most common“Normal” RBCsMost commonly denotes a non-regenerative anemiaUsually lacks RBC morphology changes“Pre-regenerative”First 1-3 days of acute loss/lysisTotal Protein can assist…
13 Macrocytic hypochromic Usually indicates a regenerative anemiaReticulocytes are relatively larger then mature RBCsHypochromic because Hgb synthesis is not completeOnly 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/MCHCAutoagglutination?Feline LeukemiaPoodles – Congenital dyserythropoiesisNot anemicLarge problem in humansB12 &/or folate deficiencyRole in veterinary medicine is questionableFelV – usually no reticsGreat Schnauzers
15 Microcytic hypochromic Consistent with an iron deficiency anemiaInadequate amount of Hgb is producedTypically seen in chronic conditionsGI blood lossSevere parasitismPSS & Hepatic atrophyMyelodysplastic syndromesCongenital: Akitas, Shiba Inu, Chow breedsNot typically hypochromicSmall RBCs (low MCV) Insufficient Hgb (low MCHC)Young dogs – GI parasites; Old dogs – GI massesInitially strongly reg. then nonLook at TPThrombocytosis can be marked
16 Bone marrow response Is there a regenerative response? Evaluation of reticulocytosisNo 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 daysWhich species do not release produce reticulocytes (horses)
17 What is consider regenerative??? Normal patient should have <45,000-60,000 absolute retic countAbsolute counts60, ,000 Early/mild response150, ,000 Mild-moderate>250, ,000 Moderate-MarkedRelative %1-4 % - Mild5-20 % - Moderate> 20 % - MarkedDefine relative
18 Regenerative anemia Loss vs. Lysis External blood loss LOOK AT TOTAL PROTEIN!!!!External blood lossLow to low-normal T.P.Hemolytic diseaseHigh to high-normal T.P.
19 Acute external blood loss PCV does not fully reflect severity first 1-3 daysReticulocytosis should start by day 3Peak reticulocytes day 4-7PCV increases to low normal w/in 2 wksMay take up to 4-5 weeks to return to normalMild anemia does not stimulate strong erythropoietin releaseSplenic contractionBlood drawsOBVIOUS – Urinary, nasal, hemoabdomen, hemothorax
20 Chronic blood lossIron deficiency and negative protein balance develops after “several” weeks in adultsOccurs more rapidly in young animals (low iron stores)Initially non/”pre” regenerativePeriod of regenerative anemia depending on severityEventually returns to being poorly/non-regenerativeOften have thrombocytosisRemember RBC indices do not change for 7-14 daysGetting blood transfusions???
21 Hemolytic anemia Hemolysis is a mechanism NOT a “disease” Lots of “non” immune mediated causesLow serum phosphorusNormal to increased T.P.Spherocytosis and/or autoagglutinationOver interpretation is commonCan be seen in diseases that are not “primary”Positive Coomb’s Test?Icterus occurs
22 Direct Coomb’s Test Identifies presence antibodies/compliment on RBCs They may/may not actually be directed towards RBCsThis may/may not actually cause damage to RBCsNeither highly specific or sensitive for IMHAPositive in 60-70% of casesPositive results – should have other evidence of IMHAEffect of steroids?**NOTE** – What is the end point of the test?????FP seen in blood transfusions, drug reactions, RBC parasitic infections
23 Breaking it down…Try to subclassify into intravascular vs. extravascularAlters differential diagnosisIntravascular – Rapid breakdown in vascular systemPink urine, pink serumHemoglobinuria best indicatorHyperbilirubinemia typically more profound then in extravascularExtravascular – removal of RBCs by spleen, liver, B.M.More commonOften has icterus, splenomegaly, hepatomegaly
24 Immune mediated “Immune-mediated” is a mechanism NOT a disease. Can be 2nd to a number of possible causesInfectious – Babesiosis, Ehrlichiosis, Leishmaniasis, Rickettsioses, Mycoplasma haemofelis, FeLVNeoplasiaDrugsCan be initially non-regenerative (esp. in cats)Drugs: Sulfas, Carprofen, cephalosporinsVax???Look alikes – ie low phosphorusAlso snake envenomation
25 “Penny” 6 year FS CockerPresented for severe lethargy, “yellow skin” and “peeing blood”Severe, macrocytic, normochromic strongly regenerative anemia with mild-moderate spherocytosisSlide agglutination negativeHigh total proteinAbdominal ultrasound WNLInfectious disease titers all negative
26 The “Penny” dilemma Needed multiple transfusion in a 5-6 day period Continued to have hemolysis despite aggressive immunosuppressive therapyWhere do we go from here???“Peeing” blood – hemoglobinuriaIntravascular hemolysisPred, cyclosporine, IVIG
27 Intravascular hemolysis Immune mediatedPhosphofructokinase deficiencyEng. Springers, Amer. CockersBabesia infectionSnake envenomationHeavy metal to toxicityZincCopperZinc dogs can have spherocytes!!!!PFK – Strenuous exercise with hyperventilation – leads to alkalosis, high pH inhibits PFK and RBC lysis
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 spherocytesAbdominal ultrasound WNLInfectious disease titers all negative
30 “Sheldon” 9 yr MC Jack Russell Presented with clinical evidence of anemiaSevere leukocytosis (54,000), severe anemia (9%), high normal platelets, mild-moderate reticulocytosisTotal Protein – 4.9 g/dLVF, Ehr. Neg.Weakness, severe lethargy, decreased appetitePale mm, tachycardia, grade 2/6 systolic murmurs
31 IHMA??? Started on prednisone, cyclosporine, doxycycline Needed 2nd transfusion 1 week laterAdded azathioprinePCV still low 2 weeks laterChest rads and abd. u/s WNLIncreased prednisone, continued on cyclosporine and azathioprine3rd transfusion in 4 weeksAdded leflunomideRepeat abdominal ultrasound WNL
32 More anemia!!! Initial PCV/TP at EAC Reference lab work 12%/4.8 Hypoalbuminemia (2.6 g/dL), globulin WNL (1.7 g/dL), BUN increased (mild), Total bilirubin (mild)Inflammatory leukogramSevere 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
35 Non-regenerative anemia Very common!!!Usually normocytic normochromicMicrocytic, hypochromic anemiasUsually no poikilocytosisHuge majority are mild-moderate in severity2nd 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?Supports bone marrow disease
37 I need more RBCs… Mild-moderate NR anemia Search for an underlying disease firstAnemia of chronic/inflammatory diseaseNeoplasia, renal disease, hepatic disease, infectious, inflammatory, endocrineDrugsPhenobarb, sulfas, methimazole, chlorambucil, azathioprine
38 Severe non-regenerative anemia ToxicityEstrogen?DrugsRenal diseaseMore than just decreased erythropoietinChronic dz, decr. RBC lifespan, ineffective production, blood lossPhenobarb, sulfas, methimazole
39 Why can’t it be easy??? Bone marrow exam Took a long time to develop Can take even longer to resolveCan still be very confusingand frustrating
40 Bone Marrow disease Immune mediated Maturation arrest vs. Pure Red Cell AplasiaMyelophthisic syndromes - multiple cell lines often affectedAplastic anemia – B.M. replaced by fatCan be 2nd to chronic ehrlichiosisMyelofibrosis – B.M. replaced by fibrousMyelonecrosis – Drugs, toxins, viralNeoplasia
41 “Howard” 9 yr MN DSH Progressive lethargy, wt. loss for several weeks Marked (12%), macrocytic, normochromic anemiaTotal protein 6.2 g/dLAbsolute reticulocyte count 40,000Retic. total 2%Corrected 0.65%FelV/FIV negativeChest 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. 20062/3 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 Transfusion More consistent with non-regenerative diseaseTransfusionRecheck 2-3 days later vs. bone marrow nowMarked erythroid hypoplasia/aplasiaImmune mediated vs. FelVBone marrow IFA positive for FelV Stutzer et al. 2010
44 RBC shape descriptions Many have little/no clinical significanceAnisocytosis, elliptocytes, codocytes, leptocytes, *echinocytes*Spherocytes – Evidence of hemolysisAcanthocytes - Hemangiosarcoma, hepatic dzSchistocytes - DIC, Fe def, CHF, myelofibrosis, hemangiosarcoma, other neoplasia
45 Summary Anemia is a common abnormality Cause can often be elusiveVital to approach systematicallyRBC indices, bone marrow response, poikilocytosisDON’T FORGET THE TOTAL PROTEIN!!!