Therapy of IMHA and IMTP

Transcription

1 Therapy of IMHA and IMTP Dr Richard K. Burchell (B.Sc. (hons), B.V.Sc., MMedVet (SAM)) Senior Lecturer, Small Animal Medicine Department of Companion Animal Clinical Studies Faculty of Veterinary Science University of Pretoria

2 Evidence Based Medicine 1976 Cockroft described the placebo effect Outcome can be wrongly ascribed to Rx Natural variation in disease outcome Variables of age, breed, gender Variables of drug formulations, route, dose What is the best therapy

3 Who cares about EBM? EBM is only about 20 years old Based on hypothesis driven research Based on principle of refuting your own theory Based on philosophy of science

4 Why is EBM important Doctors are required to give best therapy Personal experience can be misleading (biased) Helps clients understand why Rx outcome can be unpredictable Realistic expectations Paves way for novel therapy When older therapies shown to be ineffective

5 Grades of evidence

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7 Danger of not practicing EBM Flawed thinking becomes entrenched by inductive logic The white swans Wrong conclusions are made due to faulty premises Deductive logic

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9 Practical EBM Keep knowledge updates CPD, web resources Recommend therapy according to the grade CKD Diet: grade I; ACE: grade II Integrate EBM with clinical experience Keep open minded don t be arrogant about treasured recipes

10 IMHA therapy Goals of therapy Restore HCT Immunosuppression prevent complications Thromboembolism, DIC, SIRS Cornerstones of therapy Blood transfusion Immunosuppression Thrombo-prophylaxis

11 IMHA therapy Treat underlying disease Erlichia, babesia, theleria Neoplasia?

12 IMHA blood transfusions Life saving Transfusion trigger According to clinical signs Heart rate, habitus HCT above 15 (arbitrarily) Packed cells most ideal Alloantibodies uncommon in dogs

13 Immuno-suppression Glucocorticoids Azothiaprine Cyclosporine Cyclophosphamide

14 Glucocorticoids Prednisone, prednisolone, dexamethasone, triamcinilone Decrease PG synthesis Decrease chemotaxis Decrease T cell response Most effective first line immunosuppressives Grade I evidence demonstrating efficacy

15 Dose and duration?????????????? 2mg/kg OID to BID Doesn t seem to be added benefit above 2mg/kg Treat for 7 to 10 days then taper Monitor HCT while tapering

16 Side effects Pu/Pd Pp Weight gain, muscle wastage Cushing s syndrome

17 Azothiaprine Purine analog TPMT for conversion Disrupts DNA synthesis Studies have failed to show benefit over GC alone Considered steroid sparing 2mg/kg OID 30 days, then EOD

18 Side effects Very well tolerated Low SE profile BM suppression Hepatotoxicity CBC and liver enzymes ever few weeks

19 Cyclosporine Calcineurin antogonist Targeted Ththerapy Prevents activation of T cells Less widespread immune effects Dosed at 5 to 10mg/kg/day Formulation NB Effects absorbtion Must be a microemulsion

20 Cyclosporine No evidence supporting benefit Measure levels?? Poor correlation between levels and clinical response Suggested second line steroid sparing drug

21 Human gamma globulin Unknown mechanism Very expensive Small studies showed some value in refractory cases No benefit on survival Cannot be justified according to EBM

22 IMHA thrombo-prophylaxis Many die of PTE Options ULDA Clopidogrel LMW heparin Adjusted HMW heparin Dabigatran Warfarin

23 Thrombosis what does the evidence say? ULDA and Clopidogrelequally effective Adjusted Heparin likely to be the best Anti Xaassay not widely available RB prefers clopidogrel In vitro studies canine platelets and thromboxane

24 IMHA Rx overview Fluids crystalloids (electrolytes, perfusion) blood Omeprazole/ranitidine and ulsanic Cerenia/metaclopramide Doxycycline??? Imidocarb

25 Monitoring HCT/ISA/Blsm daily until discharge When HCT above 30 Then every 3 days for 10 days Start to taper HCT/CBC weekly, then bi-weekly Stop after 3 months HCT 2-3 weeks later

26 Prognosis 50-70% of primary IMHA die??? Increased number of transfusions CRP? MCP-1? TEG? Hypocoagulable TEG seems to be poor prognosis In SA prognosis is better?? More secondary IMHA?

27 IMTP therapy Immunosuppression GC first line therapy Cyclosporine been shown to be effective in humans Azonot shown to be effective

28 IMTP Vincristine? 0.02mg/kg hivg??

29 IMTP Target platelet count is above 30 to 50

30 Splenectomy Refractory recurrent cases Must be discussed with owner Babesia??