Thrombocytosis. Leukemias Cell Therapies

Transcription

1 Clinical Applications of Therapeutic Apheresis Presentation: Prof. A. Pourazar

2 TA Technologies Membrane Prisma Gambro BCT Asahi Plasma Flow Centrifugation Cascade apheresis for selective plasma component removal Specialized devices

3 Apheresis in Clinical Practice Sickle Cell Dis. Malaria Thrombocytosis RBC WBC PLT Plasma Leukemias Cell Therapies TTP Guillain Barre Syn. Myasthenia Gravis Goodpasture s Syn. Waldenstrom s

4 Bloodletting and Plasmapheresis

5 When it comes to bloodletting three questions must be answered Who? When? How much? Which Replacement fluids

6 How much? Volume of exchange plasma volume Calculation depends on numerous factors Frequency of procedures Duration of therapy

7 Efficiency of Plasmapheresis What is being removed? IgG - mainly extravascular IgM mainly intravascular Percent Efficiency of Plasmapheresis 1 plasma vol 1.5 plasma vol 2 plasma vol

8 Exchange Fluids 5% Albumin Best choice Dilute only with saline Combination of saline and albumin FFP Cryopoor plasma

9 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%

10 TTP A Thrombotic Microangiopathy Microvascular Occlusive Disorder Platelet thrombi Thrombocytopenia Mechanical damage to erythrocytes 70% of patients are women

11 TTP hyaline thrombi in glomerolus

12 TTP Mortality Rate 90% 80% 70% 60% 50% 40% 30% 20% 10% 0% Before Plasma Exchange After Plasma Exchange

13 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 antibodies to ADAMTS13

14 Plasma Exchange in TTP FFP as exchange fluid Removal of auto-antibodies antibodies to vwf multimers cleaving enzyme Infusion of vwf multimers cleaving enzyme

15 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

16 Diagnosis From Pentad to Triad Thrombocytopenia MAHA CNS symptoms Renal insufficiency Fever Thrombocytopenia MAHA LDH elevation

17 Conditions Associated with TTP 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

18 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

19 Treatment of persistent TTP Plasma exchange Corticosteroids Vincristine Rituximab Splenectomy

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

21 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 antibody to ADAMTS Response to plasma exchange equivocal results

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

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24 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

25 Goodpasture s syndrome Anti-GBM antibodies crossrective with alveolar basement membrane

26 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

27 Pauci immune GN

28 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):

29 Vasculitis

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

31 Immune Complex RPGN (MPGN)

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

33 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, /2 plasma volume exchange with 5% albumin

34 Anti-myelin Antibodies

35 GBS Clinical Course GBS course Symptom severity Time

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

37 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

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

39 Myasthenia Gravis Before plasmapheresis After Plasmapheresis

40 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

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

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

44 SLE

45 Red Cell Exchange Sickle Cell Disease Malaria Babesiosis

46 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

47 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)

48 White Cell Depletion Leukapheresis 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

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

50 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)

51 Protein A binds IgG

52 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): ): , 2004

53 Protocols for Reducing anti-hla antibodies in positive CXM and AMR IVIG 42 patients Plasmapheres is and IVIG 30% rejection episodes 89% graft survival at 2 years 62 patients 94.2% graft survival at 3 years AmJTransplant 4(7): ): , 2004

54 References Journal of Clinical Apheresis, Vol.15, No.1/2, 2000, Special Issue, Clinical Applications of Therapeutic Apheresis Journal of Clinical Apheresis APHERESIS, Principles and Practice, 2 nd Edition, Bruce McLeod Editor, AABB Press 2003