IMHA, ITP, Evans Syndrome: The Body Attacking Itself

1. IMHA, ITP, Evans Syndrome: The Body Attacking Itself Jennifer M. Pearson, DVM, MS Diplomate ACVIM (SAIM) Peak Veterinary Specialsists and Emergency October 16, 2013

2. Doctors • Internal Medicine • Dr. Jennifer M. Pearson • Dr. Sacha Mace • Surgery • Dr. Gerardo Belandria • Dr. Preson Stubbs • Dentistry • Dr. Clarence Sitzman • Emergency • Dr. Laura Halpin • Dr. Elizabeth Fogel • Dr. Nicole Vumbaco • Dr. Renea Keller • Dr. Anna Rothman

3. Technicians • Internal Medicine • Mindy Lott • Kelsey Schneider • Keeley Cook • Cassidy Martin • Susan Faulkner • Shelly Cornutt • Swing/Emergency • Alyssa Ortiz • ChelseeJacobs • Vihaney Graves • Samantha Loeber • Eric Howard • James Snedaker • Andrea Ferguson • Jami Warino

4. Other support Staff • Front Desk • Jane Snyder • Monika Scherer David Johnston • Hospital Administrator Jen Morris

5. Technicians Week!!!!!

7. Agenda • Immune system • Physiology • Immune mediated disease • Pathophysiology • Immune mediated diseases • IMHA • ITP • Evans syndrome • Others • Treatment • Prognosis

8. Immune System • It’s complicated!!!!

9. Immune system • Main function • To protect against disease (bacteria, viruses, parasites, etc) • Must differentiate the diseases from healthy tissue • Recognition of self

10. Hypersensitivity • Immune response resulting in damage to tissues • Type I • - Immediate or anaphylactic reaction (allergies) • - IgE • - mild discomfort or death • Type II • - Antigens bind to antibodies on the patients own cells • - IgM and IgG • - Marks the cell for destruction

11. Hypersensitivity (cont.) • Type III • - occurs in certain tissues • - Basically type II hypersensitivity with the activation of compliment • - very destructive to cells • Type IV • - aka delayed hypersensitivity • - takes between 2-3 days to develop • - poison ivy

12. When the immune system goes wrong • 1. Immunodeficiency: lack of normal immunity • More prone to infections • 2. Autoimmune disorders • - hyperactive immune system • - body attacks normal tissues as if they are foreign • 3. Cancer

13. Causes of Autoimmune Disorders:Primary and Secondary • Primary • Abnormal stimulation to the immune system • No Recognition of self • No underlying cause • Secondary • Underlying cause • Medications • Penicillin antibiotics • Sulfa antibiotics • Cephalosporin antibiotics • Vaccinations • Neoplasia • Hemangiosarcoma • Lymphoma • Infections • Bacterial, viral • Rickettsial

14. Initial Diagnostics • CBC w/ reticulocyte count • Chemistry profile • Urinalysis • Thoracic radiographs • Abdominal radiographs • Abdominal ultrasound

15. Specific immunologic diagnostics • Saline Autoagglutination • Coomb’s test • Platelet Autoantiobody • Antinuclear antibody • Lupus erythematosis cell detection • Rheumatoid factor

16. Signalment for Autoimmune Disorders • No sex predilection • Age • Used to be young dogs • Now no age predilection • Breeds • Cocker Spaniels • Poodles • Any breed, any age, any time any place!!!!

17. IMHA

18. Who hates IMHA???? • Resistant • Difficult to treat • Seeing more intravascular hemolysis • Standard Poodles??????

19. It’s A War • Highly inflammatory process • Ag/Ab complexes can form in different organs • Bone marrow is struggling to keep up • Organ failure • DIC

20. IMHA Clinical Signs • Weakness • Lethargy • Fever • Pallor • Icterus • Tachypnea • Exercise intolerance • Tachycardia • Anorexia • Vomiting

21. Blood work abnormalities • CBC • Elevated WBC • Anemia • Regenerative • Elevated MCV • Chemistry profile • Elevated Total bilirubin • Possibly elevated liver enzymes • Azotemia • Urinalysis • Hemoglobinuria • Hemoglobinemia • Elevated USG • Casts??

22. Anemia • Classification • Regenerative • Nonregenerative

23. Anemia • Normocytic normochromic • Bone marrow issues • Blood loss • Microcytic hypochromic • Iron deficiency anemia • GI hemorrhage • Macrocytic and normochromic • Hemolytic anemia • Hemorrhage

24. Anemia from GI Hemorrhage • Can be regenerative or nonregenerative • Microcytic /hypochromic

25. Regenerative Anemia or Nonregenerative??? • Can initially look nonregenerative • Takes the bone marrow 3-5 days to respond after acute hemorrhage or hemolysis

26. Hemolysis vs. Hemorrhage • Hemolysis • TP normal • Albumin normal • Icterus • Spherocytes • Hemorrhage • Evidence of blood loss • Low albumin • Low total protein • No icterus

27. IMHA • Extravascular hemolysis • Intravascular hemolysis

28. Extravascular hemolysis • IgG and possible IgM • Spleen is main cause for hemolysis • Spherocytes • Possible autoagglutination • Icterus

29. Spherocyte Formation

30. Intravascular Hemolysis • IgG and IgM • Activate complement • Very severe • Prognosis poor

31. Intravascular Hemolysis • Severe icterus • Hemoglobinemia • Hemoglobinuria • Severe autoagglutionation • Organ failure • DIC

32. Intravascular Hemolysis Hemoglobinuria: Portwineurine!

33. ITP Antibodies attached to platelets Destruction once released from bone marrow

34. Clinical Signs of ITP • Bleeding • Bleeding • Bleeding • Epistaxis • Scleral hemorrhage • Hematuria • Melena/Hematochezia • Petechia • Ecchymosis • Bleeding from gums • Lethargy • Weakness • Fever • Anorexia • Vomiting • W/ or w/o blood

35. Clinical Signs (cont.) • Fever • Lethargy • Petechiae • Other evidence of hemorrhage • Epistaxis • Hematuria • Bleeding from gums • Hematochezia • Hemoptosis • Scleral or ocular hemorrhage • Other

36. Thrombocytopenia • Consumption • Destruction • Loss (usually GI) • Lack of production

37. Blood Work Abnormalities • CBC • Elevated WBC • Monocytosis?? • Thrombocytopenia • +/- Anemia • Secondary to hemorrhage • Chemistry profile • Normal • Possible azotemia • Dehydration

38. How do we determine reason? • Platelet autoantibodies • Bone marrow aspirate • Response to treatment

39. Megakaryocyte

40. Evans Syndrome IMHA ITP Fairly common More difficult to treat?

41. Goals of Treatment • Treat underlying cause • Suppress the Immune system • Immediate • Long term • Support

42. Treat underlying cause • Must identify underlying cause first • Neoplasia • Bacterial infection • Rickettsial infection • Drug related • Vaccinations

43. Immunosuppressive drugs • Prednisone • 2-4mg/kg/day po bid • Cyclosporine • 5-10mg/kg po bid • Azathioprine • 1-2mg/kg /day • Cyclophosphamide • 200mg/m2 IV • Leflunomide • Methotrexate • Danazol • Gold salts

44. Other treatment • Splenectomy • Intravenous gamma globulin • Blood transfusion • Platelet rich plasma

45. Anticoagulant Tx • Low dose aspirin • 0.5mg/kg po bid • Clopidegrel • ¼ tab for a small dog q 24hrs • Extrapolate from there • Coumadin????

46. Complications • Lack of response • Life threatening hemorrhage • DIC • Organ failure • Pulmonary thromboemboli

47. Long Term Considerations • Relapses common • Long term or indefinite treatment • Avoid stimulation to immune system • No further vaccinations • Use certain medications with caution • Monitor careful in the presence of other disease

48. Prognosis • Variable • Quick response • Delayed response • Death • Relapses

49. OPEN 24/7 FOR EMERGENCY!!!!