Emergency Management of the Immune Mediated Hemolytic Anemia (IMHA) Patient. Introduction. Introduction. Introduction. VETgirl on the RUN!

Transcription

1 Emergency Management of the Immune Mediated Hemolytic Anemia (IMHA) Patient Justine Lee, DVM, DACVECC CEO, VETgirl Introduction Justine A. Lee, DVM, DACVECC, DABT CEO, VETgirl Steven Shadwick, DVM, DACVIM (Internal Medicine) Chief Medical Officer Animal Emergency & Referral Center Conflict of Interest Disclosure Introduction Garret Pachtinger, VMD, DACVECC COO, VETgirl Introduction Steven Shadwick, DVM, DACVIM Chief Medical Officer VETgirl on the RUN!! The tech-savvy way to get CE credit!! A subscription-based podcast and webinar service offering veterinary RACE-approved CE 1

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3 ! What causes IMHA? Goals of this talk! How do I recognize patients with IMHA?! Signalment! History! Clinical signs! Physical exam findings! How do I diagnose it?! Treatment modalities! Mortality/morbidity/$$$$ IMHA: Pathophysiology! RBCs coated with antibody # increased destruction of RBC IMHA Signalment! Primary! idiopathic! Secondary! Infectious! Viral! Bacterial! RBC parasite! Other immunemediated disease! Antigen! Drugs! Vaccines! Neoplasia! Older females! Middle aged! Breeds! Cocker Spaniel! Old English Sheepdog! Poodle! English Springer Spaniel! Lhasa Apso! Shih Tzu! Irish Setter! Seasonal! 40% cases between May and June! 60-75% idiopathic Historical findings Buffy, 4 yo FS Cocker! Lethargy! Weakness! Pallor! Exercise intolerance! Orange urine (snow!)! Icterus! Febrile! Anorexic! Syncope/collapse! Polydipsia 3

4 Presenting complaint:! O noticed the following clinical signs:! Orange urine (snow!)! Lethargy! Vomited once this week! Anorexia for 2 days! T: F (40.4 C)! HR: 180! Panting! Bounding pulses! Pallor! Icterus! 2/6 heart murmur Buffy s initial exam As soon as you see this, what do you do?! Full history! Thorough physical exam! Recently vaccinated?! Tick exposure? Full history! Recent meds?! TMS/Sulfas! Cephalexin! Previously transfused? Physical exam findings As soon as you see this, what do you do?! Dehydrated! Hypovolemic! Tachycardia! Tachypneic! Bounding pulses! Flow murmur! Icteric! Hepatosplenomegaly! Pallor! Febrile! Petecchia (if concurrent ITP/Evans)! Lymphadenopathy! Initial diagnostics! Big 4! PCV! TS! BG! AZO/BUN! Advanced diagnostics 4

5 Buffy s Big 4/SAG! Tells you all you need to know in < 1 minute! Other diagnostics! Filled tubes # agglutinating! PCV 15%/TS 7 g/dl (70 g/l)! Icteric & hemolyzed serum! Blood glucose 170 mg/dl (9.4 mmol/l)! SOD: stress of death!! Blood smear! Slide agglutination (SAG)! BUN 5-15 mg/dl (< 10 mmol/l)! Blood smear:! Spherocytes Clinicopathologic data! Found in 80% of IMHA patients Slide agglutination test (SAG)! 1 clean slide! 1 drop of direct blood! 1 drop of 0.9% saline! Shake! Stir! Rock! Roll! Examine slide!! 1 clean slide Slide agglutination test! 1 drop of direct blood! 1 drop of 0.9% saline! Shake! Stir! Rock! Roll! Examine slide! 5

6 What now? I think Buffy has IMHA! Prepare the owner! Cost ($2-4,000)! Prognosis! Re-occurrence! Side effects of Prednisone!! Massive pu/pd/polyphagia! Outcome! Next steps (the expensive diagnostics )! CBC Diagnostics! Chemistry (save extra serum!) 5 mls! Reticulocytes! Free catch UA (cysto only if plts/coag ok)! SNAP 4DX! Coagulation test! Free catch UA! Met CXR/AXR Diagnostics! FAST exam (chest/abdomen)! Focused abdominal sonography of trauma! 2-minute quick ultrasound! Yes fluid, no fluid! If SAG +, no need for Coombs! Therapeutic Goals 1. Perfusion, perfusion, perfusion! Treating for hypovolemia!! IVF! Blood 2. Immunomodulation 3. Prevent complications Goal #1: Perfusion, perfusion, perfusion! Start with crystalloids first! Cheap $! Life-saving! ml/kg IV balanced crystalloid over 20 minutes! Check perfusion values! Re-bolus as needed:! ml/kg IV crystalloids/20 minutes! 5 ml/kg HES IV/20 minutes 6

7 Oxygen content = CaO 2! CaO 2 = Hgb X 1.34 X SaO 2 + (0.003 X pao 2 )! i.e. IMHA with a PCV of 9%! Does it need RBC or O 2?! Does Buffy need blood or oxygen? Give Buffy a blood transfusion!! prbcs! Universal donor (A-/DEA 1.1)! Unable to blood type! ml/kg over 1-4 hours, depending on how stable. What if you don t have blood in your hospital?! Oxyglobin! Ultrapurified! Bovine! Stroma free! LRS base! Used for treatment of anemia! ml/kg (not to exceed 10 ml/kg/hr)! 10 ml/kg in dogs will raise Hg 2 g/dl = PCV 6% HBOCs: Oxyglobin! HBOCs! Colloid osmotic pressure (COP)! 40 mmhg! Fluid overload! Pigmentation changes! $! Good storage! Going out of business Goal #2: Immunosuppression! Foundation of treatment! May also be necessary for secondary IMHA! Many treatment options available! Multi-modal therapy Steroids! Inhibit release of proinflammatory cytokines! Stabilize granulocyte cell membranes! Down-regulate Fc receptor expression! Decrease response of antibody-sensitized cell functions! Decrease antigen processing! Suppress T-cell function! Induce apoptosis of T cells! Inhibit B-cell antibody production 7

8 Immunosuppression! Dex SP 0.25 mg/kg IV q. 12 while hospitalized! Don t give SC or IM! Evans syndrome (concurrent ITP?)! Slow absorption! Give IV! Immunosuppression: steroids! If patient is sick enough to hospitalize, use IV administration!! Prednisone 1-2 mg/kg PO q. 12 X MONTHS!! Dose Prednisone! 2 mg/kg/day; 40 mg/m 2 /day! Reduce by 25-50% every 2 to 4 weeks! Don t go too quickly! Based on response to treatment Prednisone Effects! Cardiovascular System: Glucocorticoids can reduce capillary permeability and enhance vasoconstriction. A relatively clinically insignificant positive inotropic effect can occur after glucocorticoid administration. Increased blood pressure can result from both the drugs vasoconstrictive properties and increased blood volume that may be produced.! Cells: Glucocorticoids inhibit fibroblast proliferation, macrophage response to migration inhibiting factor, sensitization of lymphocytes and the cellular response to mediators of inflammation. Glucocorticoids stabilize lysosomal membranes.! CNS/Autonomic Nervous System: Glucocorticoids can lower seizure threshold, alter mood and behavior, diminish the response to pyrogens, stimulate appetite and maintain alpha rhythm. Glucocorticoids are necessary for normal adrenergic receptor sensitivity.! Endocrine System: When animals are not stressed, glucocorticoids will suppress the release of ACTH from the anterior pituitary, thereby reducing or preventing the release of endogenous corticosteroids. Stress factors (e.g., renal disease, liver disease, diabetes) may sometimes nullify the suppressing aspects of exogenously administered steroids. Release of thyroid-stimulating hormone (TSH), follicle-stimulating hormone (FSH), prolactin, and luteinizing hormone (LH) may all be reduced when glucocorticoids are administered at pharmacological doses. Conversion of thyroxine (T4) to triiodothyronine (T3) may be reduced by glucocorticoids; and plasma levels of parathyroid hormone increased. Glucocorticoids may inhibit osteoblast function. Vasopressin (ADH) activity is reduced at the renal tubules and diuresis may occur. Glucocorticoids inhibit insulin binding to insulin-receptors and the post-receptor effects of insulin.! Hematopoietic System: Glucocorticoids can increase the numbers of circulating platelets, neutrophils and red blood cells, but platelet aggregation is inhibited. Decreased amounts of lymphocytes (peripheral), monocytes and eosinophils are seen as glucocorticoids can sequester these cells into the lungs and spleen and prompt decreased release from the bone marrow. Removal of old red blood cells becomes diminished. Glucocorticoids can cause involution of lymphoid tissue.! GI Tract and Hepatic System: Glucocorticoids increase the secretion of gastric acid, pepsin, and trypsin. They alter the structure of mucin and decrease mucosal cell proliferation. Iron salts and calcium absorption are decreased while fat absorption is increased. Hepatic changes can include increased fat and glycogen deposits within hepatocytes, increased serum levels of alanine aminotransferase (ALT), and gamma-glutamyl transpeptidase (GGT). Significant increases can be seen in serum alkaline phosphatase levels. Glucocorticoids can cause minor increases in BSP (bromosulfophthalein) retention time.! Immune System (also see Cells and Hematopoietic System): Glucocorticoids can decrease circulating levels of T-lymphocytes; inhibit lymphokines; inhibit neutrophil, macrophage, and monocyte migration; reduce production of interferon; inhibit phagocytosis and chemotaxis; antigen processing; and diminish intracellular killing. Specific acquired immunity is affected less than nonspecific immune responses. Glucocorticoids can also antagonize the complement cascade and mask the clinical signs of infection. Mast cells are decreased in number and histamine synthesis is suppressed. Many of these effects only occur at high or very high doses and there are species differences in response.! Metabolic effects: Glucocorticoids stimulate gluconeogenesis. Lipogenesis is enhanced in certain areas of the body (e.g., abdomen) and adipose tissue can be redistributed away from the extremities to the trunk. Fatty acids are mobilized from tissues and their oxidation is increased. Plasma levels of triglycerides, cholesterol, and glycerol are increased. Protein is mobilized from most areas of the body (not the liver).! Musculoskeletal: Glucocorticoids may cause muscular weakness (also caused if there is a lack of glucocorticoids), atrophy, and osteoporosis. Bone growth can be inhibited via growth hormone and somatomedin inhibition, increased calcium excretion and inhibition of vitamin D activation. Resorption of bone can be enhanced. Fibrocartilage growth is also inhibited.! Ophthalmic: Prolonged corticosteroid use (both systemic or topically to the eye) can cause increased intraocular pressure and glaucoma, cataracts, and exophthalmos.! Renal, Fluid, & Electrolytes: Glucocorticoids can increase potassium and calcium excretion, sodium and chloride reabsorption, and extracellular fluid volume. Hypokalemia and/or hypocalcemia rarely occur. Diuresis may develop following glucocorticoid administration.! Skin: Thinning of dermal tissue and skin atrophy can be seen with glucocorticoid therapy. Hair follicles can become distended and alopecia may occur. Copied from 8th Edition of Plumb Prednisone! Clinical response! Every study relates to glucocorticoids! Inhibits T-helper lymphocytes and downregulates proinflammatory cytokines! Dose! 3 mg/kg IV BID slow infusion! 5-10 mg/kg PO divided BID! Reduce dose by 25% every 2-4 weeks! Cost! 100 mg Atopica $ $8.00 per capsule Cyclosporine 8

9 ! GI (most common)! Gingival hyperplasia! Diabetes mellitus! Clinical response Cyclosporine! Trough serum concentrations (not usually necessary) Immunosuppression: Azathioprine! Azathioprine! Wear gloves!! When to use?! Refractory IMHA?! Cocker spaniel?! Grundy SA, Barton C, J Vet Emerg Crit Care. 2014;24(2): Azathioprine! Reduces lymphocyte numbers and T-celldependent antibody production. Greater effect on cellular vs. humoral immunity. Macrophage inhibition! Dose! 1-2 mg/kg PO q24h for 1 week, then 1-2 mg/kg PO q48h! Reduce dose by 25% every 2-4 weeks! Cost! Azathioprine 50 mg tablets: $0.50 each Azathioprine! Bone marrow suppression (q24h dosing increases risk)! GI! Pancreatitis! Hepatotoxicity! Clinical response! Leukon every 1-2 weeks initially then 1-2 months thereafter! Piek CJ, et al., BMC Vet Res 2011;13;7:15 (negative evidence)! Piek CJ, et al. J Vet Intern Med 2008; 22: ! Weinkle TK, et al. J Am Vet Med Assoc 2005;226: Mycophenolate Mofetil! Inhibits autoimmune T-cell proliferation and autoantibody production by B-cells! Dose! 10 mg/kg IV or PO BID! Reduce dose by 25% every 3-4 weeks! Cost! 250 mg capsules $1 each Mycophenolate Mofetil! Generally well-tolerated (depending on who you believe)! GI (most common)! Lymphopenia! Derm infections! Clinical response! Renal/liver panel! Electrolytes! Wang A, et al., J Small Anim Pract. 2013;54(8): ! West LD, Hart JR, J Vet Emerg Crit Care; 2014;24(2):

10 Leflunomide! Inhibits autoimmune T-cell proliferation and autoantibody production by B-cells.! Dose! 2 mg/kg PO BID! Reduce by 25% every 4 weeks! Cost! 10 mg tablets $1 each! Generally well-tolerated! Teratogenic! GI (most common)! Cytopenias! Hepatotoxicity (rare)! Clinical response Leflunomide! Bianco D, Hardy RM, J Am Anim Hosp Assoc. 2009;45(3): Human, Intravenous IgG Human, Intravenous IgG! Magic (not well understood)! Fc receptor blockade, complement blockade, autoantibody elimination, cytokine modulation, etc.! Seems to be well tolerated! Hypercoagulability has been documented! Anaphylaxis! Dose! 0.5 to 1.0 g/kg IV slowly (4 hours)! Once or more than once?! Cost! Expensive! $75-100/g! Gram of gold: $40! None! Whelan MF et al., J Vet Emerg Crit Care. 2009;19: ! Bianco D, et al., J Vet Intern Med. 2009;23: Immunosuppression: Cyclophosphamide! Immunomodulant # fallen out of favor! No improvement! CONS:! Myelosuppression! Hemorrhagic cystitis! GI upset 10

11 Immunosuppression Immunomodulation Evaluation of prognostic factors, survival rates, and treatment protocols for immune-mediated hemolytic anemia in dogs: 151 cases ( ) J Am Vet Med Assoc. June 2005;226(11): T Weinkle, SA Center, JF Randolph, KL Warner, SC Barr, HN Erb! N = 151! Cockers, MinPins, females over-represented! 30, 60, 365 day survival! Pred + AZA! Pred + AZA + ultralow-dose aspirin (ASA)! Pred + AZA + HEP! Pred + AZA + HEP + ASA Drug therapy PRED + DC 30d 365d! AZA 74% 57% 45%! AZA + ultralow-dose aspirin (ASA) 88% 82% 69%! AZA + HEP 23% 17% 17%! AZA + HEP + ASA 70% 67% 64%! Mean survival on 7 published reviews:! Discharge: 57%! 30 days: 58%! 1 year: 34% Summary of immunosuppression! Dexamethasone initially! Wean onto oral Pred! Add additional immunosuppressives if breedresistant, non-responsive! Cocker spaniel Goal #3: prevent complications! Prevent complications! Cellular hypoxia! Poor perfusion! GI ulcers! Hypercoagulable state # PTE # Hypoxemia Why do IMHA patients get GI ulcers?! High dose steroids! Shock gut! Poor perfusion GI ulcers! Treat aggressively for GI ulcers! Safe! Relatively benign! Inexpensive! H 2 -blockers! Proton-pump inhibitors! Sucralfate 11

12 ! H 2 -blockers GI ulcers! Pepcid mg/kg SID-BID (least p450)! Ranitidine 1-2 mg/kg BID (medium p450, pro-kinetic!)! Cimetidine 5-15 mg/kg QID (most p450)! Proton-pump inhibitors! Omeprazole 1 mg/kg PO SID! Pantoprazole 1 mg/kg IV SID! Sucralfate! NPO if vomiting! Does Buffy need antibiotics?! Doxycycline! 5-10 mg/kg SID or BID X 2-3 weeks! Side effects! Inactivated by milk products! Esophageal strictures! Vomiting! Light sensitivity Anti-Coagulant Therapy! Thromboembolism! Most common complication! Prevention is key ANTICOAGULANT THERAPY is lacking for current therapies Aspirin! Prevents formation of thromboxane A2 and reduces platelet aggregation! Dose (ultra-low dose)! mg/kg PO q24h! GI! Bleeding PTE: Ultra low-dose aspirin! Buffy, 12 kgs = 6 mgs aspirin!! Special compound capsules! Usually don t do concurrent NSAID + steroid, but microdose!! Weinkle TK, et al. J Am Vet Med Assoc 2005;226:

13 Heparin (Unfractionated)! Inhibit thrombin and factor Xa! Dose! 150U/kg QID initially, adjust based on anti-10a activity or PTT! Cost! Based on testing rather than medication! Bleeding Heparin (Unfractionated)! Anti-Xa activity or PTT! Helmond SE, J Vet Intern Med 2010;24(3): Low-Molecular-Weight Heparin! Inhibits factor Xa only! Dose! 0.8 mg/kg SQ QID! Cost! 20 mg dose is about $14 Low-Molecular-Weight Heparin! Bleeding (rare)! None or anti-xa activity! Panek CM, J Vet Emerg Crit Care 2015;25(2):273-7 (safe, but not rewarding) Plavix! Irreversibly alters platelet surface low-affinity ADPreceptors and reduces platelet aggregation! Dose: 2-3 mg/kg PO q24h! Cost: As low as $0.20 per 75 mg table! Bleeding! Vomiting Plavix! Mellett AM, J Vet Intern Med 2011;25(1):71-5. (no improved survival) 13

14 Red Blood Cells! RBCs have a finite lifespan! Cat: 75 days! Dog: 100 days! Normally cleared in Spleen and Liver! Reticuloendothelial system A REVIEW OF IMHA AND CHRONIC MANAGEMENT Hemolytic Anemia! Hemolytic anemia does not imply immunemediated disease! Many things can cause early termination of RBCs! Infections! Toxins! Drugs! Cancer! Congenital red-cell disease! Mechanism may or may not be immune-mediated! Mild, moderate or severe?! PCV is generally less than 20%! Regenerative or nonregenerative?! Typically regenerative! Macro-, micro-, or normocytic?! Typically macrocytic! Hyper-, hypo-, or normochromic?! Typically hypochromic Anemia! Complete blood count Anemia! Manual evaluation is VERY important! Spherocytes! Agglutination! Other abnormalities? (e.g. basophilic stippling)! Serum color! Red or icteric? Secondary IMHA! Need to rule out all causes of hemolytic anemia! Within reason and owners wishes! Thorough history and physical exam! CBC with manual smear evaluation! Spherocytes! Saline Agglutination! Coomb s test 14

15 ! Chem, UA! Thoracic Radiographs! Abdominal Radiographs! Pennies! 4Dx! Prefer NCSU tick panels! Abdominal Ultrasound Secondary IMHA! Primary IMHA! Pathogenesis! Prognosis! Treatment options IMHA! Special Considerations Primary IMHA! Middle-aged female dog! Hypochromic, macrocytic, regenerative anemia! Spherocytes! Saline agglutination positive! No history of vaccines, drugs, toxins, etc.! No evidence of underlying neoplasia! Clear of any infectious disease IMHA Pathogenesis! Type II autoimmune reaction to antigen on RBC! Binding of complement and/or antibodies! IgG or IgM! Intra- or extravascular hemolysis! Guarded prognosis! 50-70% mortality rate! Rule of 3! 1/3 die in hospital IMHA Prognosis! 1/3 go home, but relapse and die! 1/3 manage to survive! Prognostic factors are inconsistent! Intravascular >> extravascular IMHA Treatment Considerations! Blood transfusions! Immunosuppression! Anticoagulants! Finances 15

16 Prognostic factors for mortality and thromboembolism in canine immune-mediated hemolytic anemia: a retrospective study of 72 dogs J Vet Intern Med Sep-Oct;16(5): AP Carr, DL Panciera, L Kidd! N = 72 dogs! Cocker Spaniel over-represented! Clinicopathologic data:! Autoagglutination present in 42% (+ SAG)! DIC in 32%! Thromboemboli in 80% of necropsied dogs! Mortality: 58% Monitoring! Risk factors for mortality:! platelets! T BILI > 5 mg/dl! albumin! Buffy s more likely to throw a clot when:! ALKP! bilirubin! albumin! Regular monitoring is important! Hourly when critical! Daily while hospitalized! Each week after initial discharge! Bi-weekly when stable! Month-to-month, bimonthly, quarterly, semiannual, etc. Monitoring! Can be difficult for owners! Financially! Time constraints Monitoring! History and physical exam! Pale gums! Dehydration! Lethargy! Increase HR/RR! Hypertension 16

17 ! Routine Testing! PCV! CBC Monitoring! Others based on patient and current therapies! Routine Testing! PCV Monitoring! Minimum testing recommended! CBC! Preferred! Leukon/platelets may need monitoring! Spherocytes! Agglutination! Regeneration! Leukemoid reaction PCV/Hct! Normal for 4 weeks! Can consider reducing medications! Prednisone first Prednisone Effects! Cardiovascular System: Glucocorticoids can reduce capillary permeability and enhance vasoconstriction. A relatively clinically insignificant positive inotropic effect can occur after glucocorticoid administration. Increased blood pressure can result from both the drugs vasoconstrictive properties and increased blood volume that may be produced.! Cells: Glucocorticoids inhibit fibroblast proliferation, macrophage response to migration inhibiting factor, sensitization of lymphocytes and the cellular response to mediators of inflammation. Glucocorticoids stabilize lysosomal membranes.! CNS/Autonomic Nervous System: Glucocorticoids can lower seizure threshold, alter mood and behavior, diminish the response to pyrogens, stimulate appetite and maintain alpha rhythm. Glucocorticoids are necessary for normal adrenergic receptor sensitivity.! Endocrine System: When animals are not stressed, glucocorticoids will suppress the release of ACTH from the anterior pituitary, thereby reducing or preventing the release of endogenous corticosteroids. Stress factors (e.g., renal disease, liver disease, diabetes) may sometimes nullify the suppressing aspects of exogenously administered steroids. Release of thyroid-stimulating hormone (TSH), follicle-stimulating hormone (FSH), prolactin, and luteinizing hormone (LH) may all be reduced when glucocorticoids are administered at pharmacological doses. Conversion of thyroxine (T4) to triiodothyronine (T3) may be reduced by glucocorticoids; and plasma levels of parathyroid hormone increased. Glucocorticoids may inhibit osteoblast function. Vasopressin (ADH) activity is reduced at the renal tubules and diuresis may occur. Glucocorticoids inhibit insulin binding to insulin-receptors and the post-receptor effects of insulin.! Hematopoietic System: Glucocorticoids can increase the numbers of circulating platelets, neutrophils and red blood cells, but platelet aggregation is inhibited. Decreased amounts of lymphocytes (peripheral), monocytes and eosinophils are seen as glucocorticoids can sequester these cells into the lungs and spleen and prompt decreased release from the bone marrow. Removal of old red blood cells becomes diminished. Glucocorticoids can cause involution of lymphoid tissue.! GI Tract and Hepatic System: Glucocorticoids increase the secretion of gastric acid, pepsin, and trypsin. They alter the structure of mucin and decrease mucosal cell proliferation. Iron salts and calcium absorption are decreased while fat absorption is increased. Hepatic changes can include increased fat and glycogen deposits within hepatocytes, increased serum levels of alanine aminotransferase (ALT), and gamma-glutamyl transpeptidase (GGT). Significant increases can be seen in serum alkaline phosphatase levels. Glucocorticoids can cause minor increases in BSP (bromosulfophthalein) retention time.! Immune System (also see Cells and Hematopoietic System): Glucocorticoids can decrease circulating levels of T-lymphocytes; inhibit lymphokines; inhibit neutrophil, macrophage, and monocyte migration; reduce production of interferon; inhibit phagocytosis and chemotaxis; antigen processing; and diminish intracellular killing. Specific acquired immunity is affected less than nonspecific immune responses. Glucocorticoids can also antagonize the complement cascade and mask the clinical signs of infection. Mast cells are decreased in number and histamine synthesis is suppressed. Many of these effects only occur at high or very high doses and there are species differences in response.! Metabolic effects: Glucocorticoids stimulate gluconeogenesis. Lipogenesis is enhanced in certain areas of the body (e.g., abdomen) and adipose tissue can be redistributed away from the extremities to the trunk. Fatty acids are mobilized from tissues and their oxidation is increased. Plasma levels of triglycerides, cholesterol, and glycerol are increased. Protein is mobilized from most areas of the body (not the liver).! Musculoskeletal: Glucocorticoids may cause muscular weakness (also caused if there is a lack of glucocorticoids), atrophy, and osteoporosis. Bone growth can be inhibited via growth hormone and somatomedin inhibition, increased calcium excretion and inhibition of vitamin D activation. Resorption of bone can be enhanced. Fibrocartilage growth is also inhibited.! Ophthalmic: Prolonged corticosteroid use (both systemic or topically to the eye) can cause increased intraocular pressure and glaucoma, cataracts, and exophthalmos.! Renal, Fluid, & Electrolytes: Glucocorticoids can increase potassium and calcium excretion, sodium and chloride reabsorption, and extracellular fluid volume. Hypokalemia and/or hypocalcemia rarely occur. Diuresis may develop following glucocorticoid administration.! Skin: Thinning of dermal tissue and skin atrophy can be seen with glucocorticoid therapy. Hair follicles can become distended and alopecia may occur. Copied from 8th Edition of Plumb! Keep it simple Medication Changes! Don t go too quickly! Common cause for relapse! Trust your gut! Pay attention to owners! Keep it simple Medication Changes! 25% reduction of initial dose each time! 40 mg pred/day, 30/day, 20, 10, 10 EOD, Stop! Don t go too quickly! Every 2-4 weeks 17

18 ! These will happen! Minor! Major Relapses Minor Relapses! Small change in PCV! <5-6% if PCV still normal! 2-3% if PCV low! No clinical signs apparent! First step is to recheck! Same day with alternative measure! Generally recheck in 1-2 weeks! Consider previous dose Major Relapses! Large change in PCV! Drop below 25% from normal! Clinical signs may or may not be apparent! First step is to recheck! Same day with alternative measure! Consider initial effective dose! Hospitalization! prbcs! Find primary cause! Infections! Immunosuppression! Bone marrow depletion! Excessive side-effects! Financial death Complications Summary! Rule out secondary causes! Provide immediate supportive care! Blood! Start immunosuppression! I prefer dual modalities! Hourly, Daily, Weekly, etc.. Summary! Medication adjustments! Slowly! 2-4 weeks! Treat relapses based on severity 18

19 Dr. Shadwick s Preferred Treatment Protocol! prbcs as needed! g/kg Human IV IgG! 3 mg/kg cyclosporine IV over 4 hours q12h (1 to 2 days)! 5 mg/kg PO BID after that! Dexamethasone mg/kg IV q12h (1 to 2 days)! 1 mg/kg Prednisone PO BID (usually capped at 30 mg BID)! Aspirin mg/kg PO q24h! +/- Doxycycline 5 mg/kg PO BID! Identify IMHA rapidly! Client education! Treat aggressively:! Immunosuppression! Blood transfusions! Minimize antigens! GI protectants Conclusion! Prevent complications VetGirlOnTheRun# Garret@vetgirlontherun.com# Jus3ne@vetgirlontherun.com# Except as specifically noted otherwise, this material is copyrighted by VETgirl, LLC. None of the materials provided may be used, reproduced or transmitted, in whole or in part, in any form or by any means, electronic or otherwise, including photocopying, recording or the use of any information storage and retrieval system, without the consent of VETgirl, LLC. Unless expressly stated otherwise, the findings, interpretations and conclusions expressed by each presenter are their respective opinions and do not necessarily represent the views of VETgirl, LLC. Medical information here should be referenced by the practitioner prior to use. Under no circumstances shall VETgirl, LLC. be liable for any loss, damage, liability or expense incurred or suffered that is claimed to have resulted from the use of the information provided including, without limitation, any fault, error, omission, interruption or delay with respect thereto. If you have any questions regarding the information provided, please contact info@vetgirlontherun.com Check out our 2015 upcoming VETgirl appearances! Dr. Justine Lee! Merck, Chicago, July 2015! IVS, Amelia Island, July 2015! IVECCS, DC, September 2015 Dr. Garret Pachtinger! NCASAM, October 2015! GVMA, November 2015! CVC, San Diego, Dec