1 plasmapheresis - 1

7/30/2019 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

Dialysis & Transplantation 2009 February: 1-4


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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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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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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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