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Clinical Applications of Therapeutic Apheresis

Clinical Applications of Therapeutic Apheresis. Diseases Treated with TA. Guillain-Barre Syndrome 11% Myasthenia Gravis 12% CIDP 8%. Cryoglobulinemia 30% Anti-GBM Disease 30% Pauci-immune RPGN 13% SLE nephropathy 10% Myeloma kidney 7% Recurrent FSG 5% Renal transplantation 5%.

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Clinical Applications of Therapeutic Apheresis

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  1. Clinical Applications of Therapeutic Apheresis

  2. Diseases Treated with TA Guillain-Barre Syndrome 11% Myasthenia Gravis 12% CIDP 8% Cryoglobulinemia 30% Anti-GBM Disease 30% Pauci-immune RPGN 13% SLE nephropathy 10% Myeloma kidney 7% Recurrent FSG 5% Renal transplantation 5%

  3. TTP – hyaline thrombi in glomerolus

  4. TTP – Mortality Rate Before Plasma Exchange AfterPlasma Exchange

  5. Pathophysiology of TTP • Presence of Unusually Large von Willebrand Factor Multimers (ULvWFM) • Absence or low levels of ADAMTS13 (vWF cleaving metalloprotease) • Presence of auto-antibodies to ADAMTS13

  6. Plasma Exchange in TTPFFP as exchange fluid • Removal of auto-antibodies to vWF multimers cleaving enzyme • Infusion of vWF multimers cleaving enzyme

  7. Pathophysiology of TTP Normal TTP Cleaved von Willebrand Factor multimers Platelet aggregate vWF-Cleaving Enzyme Auto-antibody to vWF-Cleaving Enzyme Uncleaved unusually large vWF multimers Endothelial Cell Endothelial Cell

  8. Thrombocytopenia MAHA CNS symptoms Renal insufficiency Fever Thrombocytopenia MAHA LDH elevation DiagnosisFrom Pentad to Triad

  9. Primary (idiopathic) Secondary Systemic autoimmune disorders SLE Rheumatoid arthritis Scleroderma Polyarteritis nodosa Infectious diseases HIV infection Bacterial endocarditis Drugs Ticlopidine Clopidrogel Cyclosporine A Tacrolimus Quinine Neoplastic diseases Surgeries Cardiovascular Intestinal PBSC transplantation Pregnancy Conditions Associated with TTP

  10. Treatment of TTP • Daily plasma exchange • Exchange fluids • FFP • Cryopoor plasma • Detergent treated plasma • Treat until clinical symptoms improve and laboratory values normalize • Avoid platelet transfusions

  11. Treatment of persistent TTP • Plasma exchange • Corticosteroids • Vincristine • Rituximab • Splenectomy

  12. Treatment of relapsing TTP • Plasma exchange • Treat beyond improvement • Consider adding medications • Splenectomy • Look for other disease association

  13. TTP/HUS (Hemolytic Uremic Syndrome) • HUS • MAHA • Renal failure • Classic HUS • Childhood, Escherichia coli 0157:H7 association • Adult HUS • Renal disease is more severe • Difficult to differentiate from TTP • Platelet – fibrin thrombi • Normal ADAMTS 13 (vWF cleaving enzyme) levels • No auto-antibody to ADAMTS • Response to plasma exchange – equivocal results

  14. Rapidly Progressive Glomerulonephritis (RPGN); Crescentic Glomerulonephritis • Subacute deterioration of renal function • Crescents in glomeruli • Various etiologies

  15. Rapidly Progressive Glomerulonephritis (RPGN); Crescentic Glomerulonephritis • Goodpasture’s syndrome (Anti-Glomerular Basement Membrane Disease or Anti-GBM Disease) • Pauci immune RPGN (Wegener’s Granulomatosis or microscopic polyarteritis with antineutrophil cytoplasmic antibodies (ANCA) • RPGN with granular immune complex deposits sometimes associated with systemic vasculitis

  16. Goodpasture’s syndrome • Anti-GBM antibodies crossrective with alveolar basement membrane

  17. Goodpasture’s Syndrome • Clinical presentation • RPGN • Pulmonary hemorrhage • Anti-GBM antibodies • Treatment • Immunosuppressive drugs • Cyclophosphamide • Corticosteroids • Azathioprine • Plasmapheresis (ASFA Category I) • Daily pheresis for 14 days with 5% albumin, 1-1 ½ plasma volume • Finish procedure with 1 liter of FFP in cases with pulmonary hemorrhage and /or renal biopsy

  18. Pauci immune GN

  19. Antineutrophil Cytoplasmic Antibodies • ANCA by immunofluorescence methods • c-ANCA = Wegener’s disease (60% to 90%) • p-ANCA = microscopic polyangiitis (MPA) (50% to 80%), UC (40% to 80%), Crohn’s (10% to 40%) Hoffman GS. Arth Rheum. 1998;41(a):1521–1537.

  20. Vasculitis

  21. ANCA positive Pauci Immune RPGN • Clinical presentation • RPGN with or without pulmonary hemorrhage • Perinuclear (p-ANCA)-systemic microvasculitis • Internuclear (c-ANCA)-Wegener’s granulomatosis • Treatment • Immunosuppressive drugs • Plasmapheresis (ASFA Category II) may benefit patients with severe renal disease (Cr 9) and dialysis dependent patients

  22. Immune Complex RPGN (MPGN)

  23. Immune Complex RPGN • Clinical presentation • RPGN • Membranoproliferative GN (MPGN) • Associations • Hepatitis C • Cryoglobulinemia • Treatment • Antiviral drugs • Corticosteroids • Plasmapheresis (ASFA Category II)

  24. Acute Inflammatory Demyelinating Polyradiculoneuropathy (AIDP)Guillain-Barre Syndrome (GBS) ‘ • Pathogenesis • Anti-myelin (gangliosides) antibodies GM1, GM1b, GD1a • Clinical presentation • Ascending paralysis • “albuminocytologic dissociation” • High CSF protein • No CSF pleocytosis • 10-23% require assisted ventilation • Nerve conduction studies show demyelination • dysautonomia • Treatment • Supportive care • IVIG 400mg/kg x 5 days • Plasmapheresis (ASFA Category I) • Start within 14 days of onset • 5-6 Q.O.D. procedures, 1-1 1/2 plasma volume exchange with 5% albumin

  25. Anti-myelin Antibodies

  26. GBS Clinical Course

  27. Myasthenia Gravis Nerve Acetylcholine (Ach) Anti-AchRAb AchR Muscle

  28. Myasthenia Gravis • Clinical picture • Variable degrees of weakness; improved by rest • Thymoma in 15% of patients • Treatment • Mestinon • Prednisone • Imuran or other immunomodulatory meds • Plasmapheresis (ASFA Category I) • IVIG 400 mg/kg x 5 days • Thymectomy

  29. Myasthenia Gravis • Plasmapheresis • Acute myasthenic crisis • Respiratory insufficiency • Failure to respond to medications • Side effects of medications (prednisone) • Before and after surgery (thymectomy)

  30. Myasthenia Gravis Before plasmapheresis After Plasmapheresis

  31. Hyperviscosity Syndrome • Causes • Wadenstrom’s macroglobulinemia 50% • Multiple myeloma 5% • Clinical presentation • Neurologic symptoms • Bleeding diathesis • Retinal hemorrhage and papilledema • Hypervolemia • Congestive heart failure • Treatment • Plasmapheresis (ASFA Category II) • Chemotherapy

  32. Infectious agent V APC IL-4 , IL-6 Antibodies B-cell T-cell Plasma cell

  33. Systemic Lupus Erythematosus(SLE) • Systemic autoimmune disease with the presence of autoantibodies and immune complexes (anti-DNA, anti-DS-DNA) • Multiple organ involvement including the kidneys • Controlled clinical trials failed to show benefit from plasmapheresis in lupus nephropathy • Plasmapheresis (ASFA Category III)

  34. SLE

  35. Red Cell Exchange • Sickle Cell Disease • Malaria • Babesiosis

  36. Sickle Cell Disease • Clinical picture • Chronic genetic anemia • Hgb S instead of Hgb A alters the erythrocytes and their membranes (sickle red cells) • Increased blood viscosity • Microvascular occlusion • Infarcts in brain, lungs, retina • Pain crisis • Priapism • Acute chest syndrome • Stroke • Treatment • Red cell transfusions • Hydroxyurea • Red cell exchange (ASFA Category I) • Aims to maintain Hgb S <30

  37. Malaria • Cause • Plasmodium falciparum, vivax, ovale, malariae • Transmitted by female anopheline mosqito • Infected RBC adhere to endothelial cells of capillaries and postcapillary venules via surface knobs • Microvascular obstruction of brain, kidneys,lungs • Clinical picture • Fever, malaise, headache • Neurologic impairment • Renal failure • ARDS • Traetment • Chloroquine, quinine, quinidine • Red cell exchange (ASFA Category III) • Plasmapheresis for removal of cytokines to prevent or treat lactic acidosis, hypoglycemia (NR)

  38. White Cell DepletionLeukapheresis • Leukocytosis • Acute Myelogenous Leukemia (AML) • Chronic Myelogenous Leukemia (CML) • Acute Lymphocytic Leukemia (ALL) • Chronic Lymphocytic Leukemia (CLL) • Clinical picture • Hyperviscosity with microvascular occlusion • CNS symptoms • Hemorrhage • Pulmonary insufficiency • Treatment • Combination chemotherapy (tumor cell lysis leads to metabolic imbalance and ARDS) • Leukapheresis (ASFA Category I) • Ptreatment of leukocytosis • Prevention of tumor cell lysis syndrome

  39. Plateletpheresis 9 • Thrombocytosis (>1,000 x 10 /L) • Essential • Polycytemia vera • Clinical picture • Microvascular occlusion • CNS symptoms • Hemorrhage • Pulmonary insufficiency • Treatment • Chemotherapy • Plateletpheresis (ASFA Category I)

  40. Rheumatoid Arthritis • Chronic inflammatory autoimmune disease • Arthritis • Rheumatoid nodules • Serum rheumatoid factor • Treatment • DMARD (Disease Modifying Anti Rheumatic Drugs) • Anti-TNF alpha monoclonal antibodies • Apheresis • Plasmapheresis (ASFA Category IV) • Lymphoplasmapheresis (ASFA Category II) • Prosorba column (ASFA Category II)

  41. Protein A binds IgG

  42. Protocols for Reducing anti-HLA antibodies in positive CXM and AMR • IVIG alone • Plasmapheresis and IVIG • Plasmapheresis, IVIG and anti-CD20 antibody (splenectomy) AmJTransplant 4(7):1033-1041, 2004

  43. Protocols for Reducing anti-HLA antibodies in positive CXM and AMR AmJTransplant 4(7):1033-1041, 2004

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