1 plasmapheresis - 1
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Plasmapheresis
Dr.
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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; 7:367-86
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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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u55555555555555555555555dddd
ddddddddddddddd
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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
Prisma Gambro BCT Asahi Plasma Flow
Cascade apheresis forselective plasma componentremoval
Specialized devices
Membrane Centrifugation
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Apheresis in Clinical Practice
RBC PlasmaWBC PLT
Sickle Cell Dis.
Malaria
Leukemias
Cell Therapies
Thrombocytosis
TTP
Guillain Barre Syn.
Myasthenia GravisGoodpastures 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
intravascular0
10
20
30
40
50
60
70
Percent
Efficiency of Plasmapheresis
1 plasma vol
1.5 plasma vol
2 plasma vol
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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 treatmentof 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 neoplasticregimen improves on a more likely return of renalfunction
Evidence: CT (n=29) (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 asgood- better before onset of oligoanuria (Johnsonet 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 +/- otherimmunosuppressive agents
Recommend:
- Useful in RPGN presentation (Coppo et al. Plasma TherTransfus Technol, 1985)
- Likely minimal role in chronic disease
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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
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Cryoglobulinemia Renal Manifestations- glomerular capillary deposition
of cryoglobulin or immune complex disease withcomplement 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 reappearsafter discontinuing interferon in immediate
period when considering reintroduction of
interferon
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Hemolytic Uremic Syndrome
Difficult at times to differentiate between TTP andHUS (TTP tends to have more neurological manifestations while renalfailure predominates in HUS)
May be HUS associated with Shiga toxin, congenital(factor H deficiency) or caused by inciting drugs-cyclosporine, tacrolimus, quinine, OralContraceptives, or other diseases like SLE andcarcinoma)
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Hemolytic Uremic Syndrome
Evidence- limited-works in TTP? Why not HUS-adultoutcome usually worse
SUBGROUPS:
Recurrent HUS in renal Transplantation- (Agarwal et
al. JASN, 1995) Reviewed case reports- suggest TPEeffective but endpoint unclear (ie continue until renalfunction returns)
HUS in Children- No RCTs, case reports suggestbenefit of limiting renal damage in children with nodiarrheal prodrome, neurologic manifestations or
those >5 yrs of age (Gianviti et al. AJKD, 1993)
Recommend: Minimal data to support use except insubgroups 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 interventionshave failed
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Scleroderma
Scleroderma with ANCA positive patients,normal renin levels, normotensive associatedrenal disease
Evidence: No CTs, case reports (2)
Seemed to offer clinical improvement (Omote et al.,Inter Med, 1997)
Recommend: Consideration if poor diseasecontrol 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 intreatment 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 oftransplanted grafts
Other therapies also offered-ie monthly IVIG
infusions-currently undergoing trials Evidence: used immunoadsorption column
treatments- No CTs, some encouraging results inseveral case studies (Ross et al., Transplantation, 1993)
Recommend: High consideration in those unable toreceive 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 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
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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?
(1 5 HF BFR)
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(1.5 x HF BFR)
(0.4 x citrate rate)
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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)
HF + Plasma filtration adsorption
Ronco et al CCM 2002 30:1387-8
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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 31:1730-6)
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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
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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
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Indication of TPE
Category 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 TPE
Category 4: Lack of efficacy in controlled trials.
Examples: AIDS, amyotrophic lateralsclerosis, 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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TTPA 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 isperformed with a highly permeable filter andstandard dialysis equipment, it is oftenreferred to as membrane plasma separation
(MPS)
Having undergone considerable investigationand use in both Europe and Japan, MPS hasbecome increasingly popular in the UnitedState
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Conclusions
Nephrologists and their dialysis staff are well
trained to manage the TPE procedure
An analysis of the prevailing charges andreimbursements would suggest that providing
TPE with dialysis equipment would increase
the availability and decrease the cost of this
highly effective and potentially lifesavingprocedure
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