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Plasmapheresis. Dr. Introduction. Plasma exchange Has been used extensively for over four decades to treat a variety of renal diseases Removal of large quantities of plasma (usually 2 to 5 L) from a patient and replacement by either fresh-frozen or stored plasma

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Plasmapheresis


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    1. Plasmapheresis Dr.

    2. Introduction • Plasma exchange • Has been used extensively for over four decades to treat a variety of renal diseases • Removal of large quantities of plasma (usually 2 to 5 L) from a patient and replacement by either fresh-frozen or stored plasma • The procedure is frequently referred to as “plasmapheresis” when a solution other than plasma (e.g. , isotonic saline) is used as replacement fluid • (“apheresis” from the Greek for “to remove” or “to take away”)

    3. Introduction • Apheresis technology was Initially developed in the 1950s to harvest peripheral blood cells from healthy donors for transfusion into patients • Renal indications for therapeutic plasma exchange (TPE) continue to expand • Nephrologists are well trained to perform this extracorporeal blood purification treatment Dialysis & Transplantation 2009 February: 1-4

    4. Renal indications Dialysis & Transplantation 2009 February: 1-4

    5. J. Am. Soc. Nephrol. 1996; 7:367-86

    6. Plasmapheresis • Method of treatment in which the plasma components separated with a plasma separator are subjected to plasma exchange (PE), plasma adsorption, double-filtration plasmapheresis with a secondary membrane, and other treatments Dialysis & Transplantation 2009 February: 1-4

    7. u55555555555555555555555ddddddddddddddddddd Dialysis & Transplantation 2009 February: 1-4

    8. Technical considerations • Today automated methods for cell separation are available, • These systems are essentially of two types: • 1. Centrifugation • 2. Plasma filtration

    9. Technical considerations

    10. Technical considerations

    11. Technical considerations

    12. Technical considerations

    13. Technical considerations Dialysis & Transplantation 2009 February: 1-4

    14. Dialysis & Transplantation 2009 February: 1-4

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

    16. Dialysis & Transplantation 2009 February: 1-4

    17. 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

    18. Bloodletting and Plasmapheresis

    19. “When it comes to bloodletting three questions must be answered” • Who? • When? • How much? Which Replacement fluids

    20. How much? • Volume of exchange • 1-1.5 plasma volume • Calculation depends on numerous factors • Frequency of procedures • Duration of therapy

    21. Efficiency of Plasmapheresis • What is being removed? • IgG - mainly extravascular • IgM – mainly intravascular

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

    23. Mechanical Removal of Antibodies • When antibody is rapidly and massively decreased by TPE, antibody synthesis increases rapidly. • This rebound response complicates treatment of autoimmune diseases. • It is usually combined with immune suppressive therapy.

    24. Goodpasture’s Syndrome • Anti-glomerular Basement Membrane Antibody Mediated Disease • Single CT (Johnson et al. Medicine 1985), case studies • TPE useful in rapid lowering of Anti-GBM Ab • Lower post-treatment serum creatinine, decreased incidence of ESRD • NEED ADJUNCT IMMUNOSUPPRESSIVE REGIMEN • Follow antibody levels for end point

    25. Rapidly Progressive GN (non Anti-GBM) • RPGN- most patients have evidence of antibody associated disease (ANCA), or known immune complex disease - IgA, Cryoglobulinemia,lupus • Case reports (favorable), CT-no favorable generalized benefit (Cole et al. 1992, AJKD) (when TPE added to standard immunosuppressive therapy)

    26. Rapidly Progressive GN (non Anti-GBM) • However: • Subset analysis revealed that TPE was beneficial for patients with severe disease or those requiring dialysis (Kaplan Ther Apheresis, 1997)

    27. American Journal of Kidney Diseases, 2008: 52(6):1180-96

    28. Multiple Myeloma with Renal Failure • Cast Nephropathy resulting from light chain toxicity • TPE in conjunction with proper anti neoplastic regimen improves on a more likely return of renal function • Evidence: CT (n=29) (Zucchelli et al. KI, 1988)- strong support • Recommend- 5 consecutive daily TPE treatments-early in course

    29. Multiple Myeloma with Renal Failure • Caveats: • Must rule out other causes of renal failure as these patients tend to be relatively ill • If renal failure well established- results not as good- better before onset of oligoanuria (Johnson et al. Arch Intern med, 1990)

    30. IgA Nephropathy & Henoch Schonlein Purpura • ~ 10% of IgA presents as RPGN • TPE rationale--removal of circulating IgA • Evidence No CTs, case reports Treatment +/- other immunosuppressive agents • Recommend: • Useful in RPGN presentation (Coppo et al. Plasma Ther Transfus Technol, 1985) • Likely minimal role in chronic disease

    31. HSP(Hattori et al, Am J Kid Dis, 1999, 33:427-33) • 9 children with RPGN with HSP Rx with PP without immunosuppression • Proteinuria ~ 4.9 gms/m2 • GFR ~ 46 mls/min/1.73 m2 • 6/9 complete recovery • 2/9 rebound with proteinuria with progression to ESRD

    32. Cryoglobulinemia • Renal Manifestations- glomerular capillary deposition of cryoglobulin or immune complex disease with complement activation and vasculitis • Evidence: No CTs, case reports and uncontrolled trials • Consensus: Useful adjunct in treatment of severe disease (progressive RF, coalescing purpura, advanced neuropathy) (D’Amico et al. KI, 1989)

    33. Cryoglobulinemia • Caveat: • If Hep C associated disease interferon-alpha used as treatment (Misiani et al. NEJM, 1994) • Can use TPE as adjunct if disease reappears after discontinuing interferon in immediate period when considering reintroduction of interferon

    34. Hemolytic Uremic Syndrome • Difficult at times to differentiate between TTP and HUS (TTP tends to have more neurological manifestations while renal failure predominates in HUS) • May be HUS associated with Shiga toxin, congenital (factor H deficiency) or caused by inciting drugs-cyclosporine, tacrolimus, quinine, Oral Contraceptives, or other diseases like SLE and carcinoma)

    35. Hemolytic Uremic Syndrome • Evidence- limited-works in TTP? Why not HUS-adult outcome usually worse • SUBGROUPS: • Recurrent HUS in renal Transplantation- (Agarwal et al. JASN, 1995) Reviewed case reports- suggest TPE effective but endpoint unclear (ie continue until renal function returns) • HUS in Children- No RCTs, case reports suggest benefit of limiting renal damage in children with no diarrheal prodrome, neurologic manifestations or those >5 yrs of age (Gianviti et al. AJKD, 1993) • Recommend: Minimal data to support use except in subgroups above

    36. Systemic Lupus Erythematosus • Evidence- early case reports suggested some benefit but CTs have not supported TPE when added to standard Immunosuppression (Lewis et al., NEJM, 1992) • May be some role in pregnancy when use of cytotoxic agents are not desired • ? Treatment refractory disease • Recommend: no evidence to support use

    37. Antiphospholipid Antibody Syndrome, Anticardiolipin Antibodies, Lupus anticoagulant • Associated with venous & arterial thrombosis, fetal loss and occasional renal disease • Evidence- no CTs, case reports • Limited in renal disease- some benefit noted in patients treated for LA pregnancy associated thrombotic microangiopathy (Farrugia et al., AJKD 1992) • Recommend: May be useful when other interventions have failed

    38. Scleroderma • Scleroderma with ANCA positive patients, normal renin levels, normotensive associated renal disease • Evidence: No CTs, case reports (2) • Seemed to offer clinical improvement (Omote et al., Inter Med, 1997) • Recommend: Consideration if poor disease control and patient ANCA positive

    39. Focal Segmental Glomerulosclerosis • Group: Recurrence Post-transplant (15-55% recurrence)- thought to be due to a circulating factor not yet specifically isolated • Evidence - strong no CTs, case reports with clinical and proteinuria improvement (Artero et al., AJKD, 1994) • Recommend: Daily therapy (early) for up to 2 weeks

    40. Focal Segmental Glomerulosclerosis • Group: Native FSGS • Multiple etiologies, therefore need to evaluate carefully • Evidence: equivocal- may offer benefit in treatment resistant forms of primary FSGS • Recommend: Clinically based

    41. Panel Reactive Antibody Reduction • Transplant Candidates with high titers of cytotoxic antibodies- high rate of hyperacute rejection of transplanted grafts • Other therapies also offered-ie monthly IVIG infusions-currently undergoing trials • Evidence: used immunoadsorption column treatments- No CTs, some encouraging results in several case studies (Ross et al., Transplantation, 1993) • Recommend: High consideration in those unable to receive renal transplants due to elevated PRA

    42. Acute Renal Vascular Rejection • Evidence: 2 controlled trials no significant benefit noted (Allen et al., Transplantation, 1983) • Recommend: No supportive evidence for TPE in this treatment

    43. Acute Hepatic Failure(Singer et al, Ann Surg, 2001 234:418-24) • 49 children with FHF Rx with PP for • Hepatic support for recovery/bridge to Tx • Correction of coagulation • Results • 3/49 (8%) complete recovery • 32/49 (64%) bridge to Tx • 14/49 (28%) died due to FHF • No complications from PP

    44. PP with or without HF in Sepsis • New generation of HF machines now have capability for PP • Can be done simultaneously with HF with all current machinery • Does data exist in this area?

    45. (1.5 x HF BFR) (0.4 x citrate rate)

    46. HF + Plasma filtration adsorption • 10 pts with SS • 10 hrs of PFA + CVVHD vs CVVHD alone • MAP > with PFA (p = 0.001) • 11.8 vs 5.5 mmHg • Norepi < with PFA (P =0.003 ) • 0.08 vs 0.005 • TNF alpha production > with PFA (p = 0.009) Ronco et al CCM 2002 30:1387-8

    47. Plasma exchange and sepsis • 76 adult pts with DIC/MOSF/ARF-66% • Ventilated-72% • Shock-88% • Rx with PE until DIC reversed • Avg 2 (range 1-14) • Predicted mortality rate ~ 80% with Survival rate 82% (Stegmayr et al CCM 2003 31:1730-6)

    48. Sepsis Rx with PE • Tetta C et al • Nephrol Dial Transpl 1998 13:1458-64 • Use of sorbent adsorption for cytokine removal • Nguyen el al Ped CCM 2001 2:187-196 • Rx with PE for Rx of microvascular thrombosis

    49. Sepsis Rx with PE • Winchester et al Blood Purif 21:79-84 • Use of target sorbents • Tetta el al • Ther Apher 2002 :109-15 • Int Care Med 2003 29:1222-8 • Artif Organs 2003 27:202-13 • Sorbents, adsorption, PE