Plasmapheresis

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Plasmapheresis

• Dr. Anand Banka
• PGI

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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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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

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Renal indications
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J. Am. Soc. Nephrol. 1996 7367-86
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• 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

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Technical considerations

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

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Technical considerations
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• Technical considerations

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Technical considerations
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Technical considerations
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Technical considerations
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TA Technologies
Membrane
Centrifugation

• Prisma Gambro BCT
• Asahi Plasma Flow
• Cascade apheresis for selective plasma component
  removal
• Specialized devices

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Apheresis in Clinical Practice
Sickle Cell Dis. Malaria
Thrombocytosis
RBC
Plasma
WBC
PLT
Leukemias Cell Therapies
TTP Guillain Barre Syn. Myasthenia
Gravis Goodpastures Syn. Waldenstroms
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Bloodletting and Plasmapheresis
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When it comes to bloodletting three questions
must be answered

• Who?
• When?
• How much?

Which Replacement fluids
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How much?

• Volume of exchange
• 1-1.5 plasma volume
• Calculation depends on numerous factors
• Frequency of procedures
• Duration of therapy

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Efficiency of Plasmapheresis

• What is being removed?
• IgG - mainly extravascular
• IgM mainly intravascular

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Exchange Fluids

• 5 Albumin
• Best choice
• Dilute only with saline
• Combination of saline and albumin
• FFP
• Cryopoor plasma

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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.

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Goodpastures 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

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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)

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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)

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American Journal of Kidney Diseases, 2008
52(6)1180-96
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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 (n29) (Zucchelli et al. KI, 1988)-
  strong support
• Recommend- 5 consecutive daily TPE
  treatments-early in course

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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)

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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

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HSP(Hattori et al, Am J Kid Dis, 1999, 33427-33)

• 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

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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) (DAmico et al. KI, 1989)

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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

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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)

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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 gt5 yrs of age (Gianviti et al. AJKD,
  1993)
• Recommend Minimal data to support use except in
  subgroups above

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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

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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

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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

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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

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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

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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

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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

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Acute Hepatic Failure(Singer et al, Ann Surg,
2001 234418-24)

• 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

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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?

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(1.5 x HF BFR)
(0.4 x citrate rate)
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HF Plasma filtration adsorption

• 10 pts with SS
• 10 hrs of PFA CVVHD vs CVVHD alone
• MAP gt with PFA (p 0.001)
• 11.8 vs 5.5 mmHg
• Norepi lt with PFA (P 0.003 )
• 0.08 vs 0.005
• TNF alpha production gt with PFA (p 0.009)

Ronco et al CCM 2002 301387-8
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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 311730-6)
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Sepsis Rx with PE

• Tetta C et al
• Nephrol Dial Transpl 1998 131458-64
• Use of sorbent adsorption for cytokine removal
• Nguyen el al Ped CCM 2001 2187-196
• Rx with PE for Rx of microvascular thrombosis

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Sepsis Rx with PE

• Winchester et al Blood Purif 2179-84
• Use of target sorbents
• Tetta el al
• Ther Apher 2002 109-15
• Int Care Med 2003 291222-8
• Artif Organs 2003 27202-13
• Sorbents, adsorption, PE

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Indication of TPECategory 1 Standard
acceptable therapy

• Chronic idiopathic demyelinating polyneuropathy
  (CIDP), cryoglobulinemia, Goodpastures syndrome,
  Guillain-Barre syndrome, focal segmental
  glomerulonephritis, hyperviscosity, myasthenia
  gravis, post transfusion purpura, Refsums
  disease, TTP

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Indication of TPECategory 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

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Indication of TPECategory 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.

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Indication of TPECategory 4 Lack of efficacy
in controlled trials.

• Examples AIDS, amyotrophic lateral sclerosis,
  lupus nephritis, psoriasis, renal transplant
  rejection, schizophrenia, rheumatoid arthritis

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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?

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TTP A Thrombotic Microangiopathy

• Microvascular Occlusive Disorder
• Platelet thrombi
• Thrombocytopenia
• Mechanical damage to erythrocytes
• 70 of patients are women

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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

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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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Thank You!