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Plasmapheresis Dr. Anand Banka PGI. Introduction Plasma exchange Has been used extensively for over four decades to treat a variety of renal diseases.

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Presentation on theme: "Plasmapheresis Dr. Anand Banka PGI. Introduction Plasma exchange Has been used extensively for over four decades to treat a variety of renal diseases."— Presentation transcript:

1 Plasmapheresis Dr. Anand Banka PGI

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”)

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4 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

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

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

7 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

8 u dddd ddddddddddddddd Dialysis & Transplantation 2009 February: 1-4

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

10 Technical considerations

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14 Dialysis & Transplantation 2009 February: 1-4

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16 TA Technologies Prisma Gambro BCT Asahi Plasma Flow Cascade apheresis for selective plasma component removal Specialized devices MembraneCentrifugation

17 Dialysis & Transplantation 2009 February: 1-4

18 Apheresis in Clinical Practice RBCPlasmaWBCPLT Sickle Cell Dis. Malaria Leukemias Cell Therapies Thrombocytosis TTP Guillain Barre Syn. Myasthenia Gravis Goodpasture’s Syn. Waldenstrom’s

19 Bloodletting and Plasmapheresis

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

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

22 Efficiency of Plasmapheresis What is being removed? IgG - mainly extravascular IgM – mainly intravascular

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

24 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.

25 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

26 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)

27 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)

28 American Journal of Kidney Diseases, 2008: 52(6):

29 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

30 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)

31 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

32 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

33 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)

34 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

35 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)

36 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

37 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

38 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

39 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

40 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

41 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

42 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

43 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

44 Acute Hepatic Failure (Singer et al, Ann Surg, :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

45 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?

46 (1.5 x HF BFR) (0.4 x citrate rate)

47 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 TNF alpha production > with PFA (p = 0.009) HF + Plasma filtration adsorption Ronco et al CCM :1387-8

48 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 :1730-6)

49 Sepsis Rx with PE Tetta C et al Nephrol Dial Transpl : Use of sorbent adsorption for cytokine removal Nguyen el al Ped CCM : Rx with PE for Rx of microvascular thrombosis

50 Sepsis Rx with PE Winchester et al Blood Purif 21:79-84 Use of target sorbents Tetta el al Ther Apher 2002 : Int Care Med : Artif Organs : Sorbents, adsorption, PE

51 Indication of TPE Category 1: Standard acceptable therapy Chronic idiopathic demyelinating polyneuropathy (CIDP), cryoglobulinemia, Goodpasture’s syndrome, Guillain-Barre syndrome, focal segmental glomerulonephritis, hyperviscosity, myasthenia gravis, post transfusion purpura, Refsum’s disease, TTP

52 Indication of TPE Category 2: Sufficient evidence to suggest efficacy usually as adjunctive therapy ABO incompatible organ transplant, bullous pemphigoid, coagulation factor inhibitors, drug overdose and poisoning (protein bound), Eaton- Lambert syndrome, HUS, monoclonal gammopahty of undetermined significance with neuropathy, pediatric autoimmune neuropsychiatric disorder associated with streptococcus, RPGN, systemic vasculitis

53 Indication of TPE Category 3: Inconclusive evidence of efficacy or uncertain risk/benefit ratio. TPE can be considered for the following occasions: Standard therapies have failed. Disease is active or progressive. There is a marker to follow. It is agreed that it is a trial of TPE and when to stop. Possibility of no efficacy is understood by the patient.

54 Indication of TPE Category 4: Lack of efficacy in controlled trials. Examples: AIDS, amyotrophic lateral sclerosis, lupus nephritis, psoriasis, renal transplant rejection, schizophrenia, rheumatoid arthritis

55 Risk Benefit ratios Difficulty of basing all decision on patient care on controlled trial data (retrospective or prospective) is that one will not advance thought process If the therapy has known and controlled risks and is safe then do not the potential benefits potentially out weigh the risks?

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

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59 TPE with Dialysis Equipment When therapeutic plasma exchange is performed with a highly permeable filter and standard dialysis equipment, it is often referred to as membrane plasma separation (MPS) Having undergone considerable investigation and use in both Europe and Japan, MPS has become increasingly popular in the United State Dialysis & Transplantation 2009 February: 1-4

60 Conclusions Nephrologists and their dialysis staff are well trained to manage the TPE procedure An analysis of the prevailing charges and reimbursements would suggest that providing TPE with dialysis equipment would increase the availability and decrease the cost of this highly effective and potentially lifesaving procedure

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