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THERAPEUTIC APHERESIS

J. Sennesael

Department of Nephrology, UZ Brussel

23-03-2013

Presentation Overview

Definition of therapeutic apheresis

Apheresis methods

Mechanism of action of therapeutic plasma exchange (TPE)

Kinetics of TPE

Indications for TPE

TPE in renal diseases

TPE in neurological diseases

Complications of TPE

DEFINITION OF THERAPEUTIC APHERESIS

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Definition of Therapeutic Apheresis

Procedure name Description

Leukocytapheresis A procedure in which the WBCs are separated from the blood.

The cells may be discarded (acute leukemia) or used for

transfusion (hematopoietic progenitor cells)

Thrombocytapheresis A therapeutic procedure in which platelets are removed and

discarded from a thrombocythemic patient.

RBC exchange A therapeutic procedure in which abnormal RBCs are removed

and replaced by donated RBCs.

Plasmapheresis A procedure in which plasma is separated from the blood and

returned without replacing the removed volume.

Plasma exchange A procedure in which a large volume of plasma is removed,

usually 1-1.5 plasma volumes. The removed plasma is replaced

with a replacement fluid.

LDL apheresis A type of plasmapheresis procedure in which the removed

plasma is modified to remove LDL cholesterol and then

returned to the patient.

Apheresis < gr. aphaeresis: taking away, to carry

Commonly performed apheresis procedures

Adapted from JL Winters, Hematology 2012

APHERESIS METHODS

TPE Methods

Centrifugation-based TPE

Centrifugal force separates

cells from plasma based on

their specific gravity

Hematology/Bloodbank

Filtration-based TPE

High permeable membrane

separates plasma from

cellular components

Nephrology

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Filtration-based TPE

Standard dialysis machine

HDF mode, low volume

High permeable membrane (MWC0 3000 kD)

High Permeable Membranes for TPE

Gambro plasma filter

PF1000 (0.15 m², ETO)

Filtration 25 ml/min (1.5 l/h)

Asahi plasmaflo

Polyethylene (copolymer coating)

OP-02 (0.2 m², gamma)

Filtration 20 - 40 ml/m

OP-5W (0.50 m², gamma)

Filtration 40-60 ml/m

(1 unit FFP 250 ml)

Apheresis Methods

Method Pro Con

• No loss of platelets

• Less extracorporeal

volume

• Heparin (usually)

• Dialysis catheter needed

• Substance removal

depends on membrane

• Higher blood flow rate

• Loss of platelets

• Greater extracorporeal

volume

• Citrate anticoagulation

• Peripheral blood line

sufficient

• Can separate any blood

component

• Lower blood flow rate

Centrifugation

Filtration

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MECHANISM OF ACTION OF TPE

Mechanism of Action of Plasma Exchange

1. Removal of known pathogenic substances from plasma

Autoantibody: Thrombotic thrombocytopenic purpura (TTP), immune thrombocytopenic purpura (ITP), myasthenia gravis

(MG), Guillain-Barré syndrome (GBS), neuromyelitis optica (NMO), anti-GBM glomerulonephritis (and

Goodpasture’s syndrome), ANCA-associated glomerulonephritis (and Wegener’s granulomatosis),

antiphospholipid crisis etc.

Probable autoantibody:

Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), multiple sclerosis (MS), etc.

Antigen-antibody complexes:

Hepatitis C vasculitis, systemic lupus erythematosus, etc.

Alloantibody:

Transplant sensitization, transplant rejection (humoral), transfusion reactions, etc.

Paraproteins:

Waldenstrom’s, hyperviscosity, light-chain neuropathy, light-chain glomerulopathy, myeloma cast

nephropathy, etc.

Non-Ig proteins:

Focal segmental glomerulosclerosis (FSGS)

Endogenous toxins:

Hypercholesterolemia, liver failure, systemic inflammatory response syndrome (SIRS), etc.

Exogenous poisons:

Amanita (mushroom), drugs, etc.

DM Ward, J Clin Apher 2011

Mechanism of Action of Plasma Exchange

2. Restoration of deficient factors

ADAMTS 13 in TTP

Complement factors in aHUS

3. Immunomodulatory effects

Th1/Th

2 modulation: shift towards TH

2

(1)

Suppression of IL-2 & IFN-gamma production(2)

Increased Concanavalin A-induced suppressor function

(1) H Goto, Ther Apher 2001; (2) S Shariatmadar, Am J Hematol 2005

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KINETICS OF TPE

Kinetics of Plasma Exchange

DM Ward, J Clin Apher 2011

Plasma Volume Exchange

Plasma Volume Exchange Percent Removed

0 100%

0.5 39.3%

1.0 63.2%

1.5 77.7%

2.0 86.5%

2.5 91.8%

3.0 95.0%

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Calculating Volumes

EXCHANGE VOLUME CALCULATED RELATIVE TO THE

ESTIMATED PLASMA VOLUME (EPV):

EPV(L) = 0.07 x weight (kg) x (1-hematoctrit)

Ex: 80 kg male with Hct of 30 (0.3):

EPV = 0.07 x 80 x 0.7 = 3.92 liter

1.5 plasma volumes = 3.92 x 1.5 = 5.9 liter

60 kg female with Hct of 35 (0.35):

EPV = 0.07 x 60 x 0.65 = 2.73 liter

1.5 plasma volumes = 2.73 x 1.5 = 4.1 liter

Number and Frequency of Treatments

Underlying disease

(daily in TTP, severe anti-GBM disease)

Type of molecule

IgM (75% intravascular): easily removed (90% in 2 sessions)

IgG (45% intravascular): less easily removed (90% in 5 sessions)

rebound phenomenon

Desired endpoint

(clinical improvement; reduction of specific substance)

IN GENERAL: 5-7 sessions over 10 days, then pause and reassess

M Ward, J Clin Apher 2011

Removal of Normal Plasma Components

Coagulation factors

Decline in F VIII, F IX, VWF (till 4 hours post PE)

in F V, F VII, F X (till 24 hours post PE)

Fibrinogen: 66% of pre-apheresis levels by 72 hours

Inhibitors of coagulation

Antithrombin

Pseudocholinesterase

Reduced metabolism of some drugs

Prolonged neuromuscular blockade

Antimicrobial Abs

False negative test for infectious diseases

Drugs

Ceftriaxone, ceftazidime, tobramycin, cisplatin, vincristine, diltiazem,

Verapamil, propoxyphene, propranolol, rituximab, IFN-alfa

Adapted from JL Winters, Hematology 2012

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Replacement Fluids

5% Albumin or Albumin/Saline Fresh frozen plasma

• No depletion coagulopathy

• No depletion of IgG

• Citrate-related problems

(hypocalcemia, metabolic alcalosis)

• Anaphylactic reactions

• Viral transmission

• False positive testing for viral Ab

• No viral transmission

• Rare reactions

• Expensive

• Depletion coagulopathy

• Depletion IgG

• Hypokalaemia

INDICATIONS FOR TPE

American Society for Apheresis

Journal of Clinical Apheresis

Volume 25- Issue 3- 2010

Guidelines on the use of Therapeutic

Apheresis in clinical practice – Evidence

based approach (Szczepiorkowski ZM et al.)

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ASFA Guidelines

Categories – Redefinition of the Indications

Evidence-Based Assessment of the

Therapeutic Apheresis Literature

Recommendations-Sub-Categories

Focus on Treatment Approach to a given

Clinical Condition

Fact Sheets

ASFA Categories

Category I: Apheresis is accepted as

first-line therapy

(Primary of in conjunction with other modes

of treatment)

GRADE 1A: Strongly recommended, high quality evidence

GRADE 1B: Strongly recommended, moderate quality evidence

GRADE 1C: Strongly recommended, low to very low quality

evidence

ASFA Categories

Category II: Apheresis is accepted as

second-line therapy, either as

standalone treatment or in conjunction

with other modes of treatment

GRADE 2A: Weak recommended, high quality evidence

GRADE 2B: Weak recommended, moderate quality evidence

GRADE 2C: Weak recommended, low to very low quality

evidence

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ASFA Categories

Category III: Optimum role of Apheresis

is not established. Decision making

should be individualized

Category IV: Published evidence

demonstrates or suggests Apheresis

to be ineffective or harmful. IRB

approval is desired

Indications for TPE

Renal

ANCA-associated RPGN (dialysis dependence, DAH)

Anti-GBM disease (dialysis independence, DAH)

Recurrent FSGS

aHUS (auto-Ab to factor H)

Ab-mediated transplant rejection

Neurological

Guillain-Barré syndrome

Chronic idiopathic demyelinating polyneuropathy (CIDP)

Myasthenia gravis

Paraproteinemic polyneuropathy (IgG/IgA; IgM)

Adapted from Szczepiorkowski ZM, 2010

Category I: Standard acceptable therapy

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Autoimmune

Cryoglobulinemia (severe, symptomatic)

Haematological

Thrombotic thrombocytopenic purpura (TTP)

Hyperviscosity in monoclonal gammopathies

Indications for TPE

Adapted from Szczepiorkowski ZM, 2010

Category I: Standard acceptable therapy

Indications for TPE

Renal

aHUS (Complement factor gene mutation)

ABO incompatible kidney transplantation

Desensitisation for DSA

Myeloma cast nephropathy

Neurological

Acute disseminated encephalomyelitis

Chronic focal encephalomyelitis (Rasmussen’s)

Lambert-Eaton myasthenic syndrome

Multiple Sclerosis (acute disease, steroid resistant)

Neuromyelitis Optica (Devic’s syndrome)

Adapted from Szczepiorkowski ZM, 2010

Category II: Sufficient evidence to suggest

efficacy as adjunctive therapy

Autoimmune

Catastrophic anti-phospholipid syndrome

Cryoglobulinemia (secondary to HCV)

Haematological

Pure red cell aplasia

Cold agglutinin disease (life threatening)

Red cell alloimmunisation in pregnancy

Poisoning/overdosing

Mushroom poisoning

Phytanic acid storage disease (Refsum’s disease)

Indications for TPE

Adapted from Szczepiorkowski ZM, 2010

Category II: Sufficient evidence to suggest

efficacy as adjunctive therapy

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Indications for TPE

Renal

Immune complex RPGN

Nephrogenic systemic fibrosis

Category III: Inconclusive evidence of

efficacy or uncertain risk/benefit ratio

Neurological

Multiple sclerosis (chronic progressive)

Paraneoplastic neurologic syndromes

Haematological

Autoimmune hemolytic and aplastic anemia

TMA (calcineurininhibitors, HSCT)

Autoimmune

Systemic sclerosis

Adapted from Szczepiorkowski ZM, 2010

Indications for TPE

Category III: Inconclusive evidence of

efficacy or uncertain risk/benefit ratio

TPE can be considered for the following occasions:

1. Standard therapies have failed

2. Disease is active or progressive

3. There is a marker to follow

4. It is agreed that it is a trial of TPE and when to stop

5. Possibility of no efficacy is understood by the patient

Indications for TPE

Category IV: Lack of efficacy in controlled trials

Renal

Goodpasture syndrome (dialysis dependent, no DAH)

HUS (diarrhea associated, typical)

Haematological

TMA (gemcitabine, quinine)

Coagulation factor inhibitors

Autoimmune

Rheumatoid arthritis (refractory)

Dermato-/polymyositis

Pemphigus

Neurological

Amyotrophic lateral sclerosis

Inclusion body myositis

Adapted from Szczepiorkowski ZM, 2010

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TPE IN RENAL DISEASES

TPE in renal diseases

Thrombotic microangiopathy

Anti-glomerular basement membrane disease

ANCA-associated vasculitis

Hyperviscosity syndromes

Cryoglobulinemia

Recurrent FSGS

Antibody mediated rejection

Thrombotic Microangiopathy

Clinical manifestations Laboratory abnormalities

Renal failure

Neurologic deficits

Fever Thrombocytopenia

(No DIC)

Microangiopathic

hemolytic anemia

schistocytes

LDH

haptoglobin

TTP/HUS

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TPE in Thrombotic Microangiopathy

Subgroup Response to TPE (%)

TTP

Primary

Hereditary (ADAMTS 13 activity < 10%)

Idiopathic or acquired

80-90

80-90

Secondary

Drugs (except mitomycin C)

Collagen vascular disease

Infection (except E. coli)

Pregnancy

Pancreatitis

Stem cell transplant

Malignancy

Malignant hypertension

80-90

50-70

50-70

50-70

50-70

0

0

0

Adapted from Clark WF, Sem Dial 2012

TPE in Thrombotic Microangiopathy

Subgroup Response to TPE (%)

HUS

Primary: atypical HUS (aHUS)

Complement factor H, I or B

C3 convertase, thrombomodulin

Membrane co-factor protein (MCP-CD46)

50-70

50-70

0

Secondary: diarrheal HUS (DHUS)

E. coli O157: H7 (STEC) 0

Adapted from Clark WF, Sem Dial 2012

Thrombotic Microangiopathy: Adult

TTP/HUS

Test ADAMTS 13

Stool cultures E. coli O157: H7

Start TPE

DIC

Test INR, PT, D-dimer

Secondary (50%)

TPE 50-70% response

Collagen vascular

disease, drugs,

pregnancy,

pancreatitis

NO TPE for stem

cell transplant,

malignancy,

mitomycin C

Idiopathic (50%)

TPE 80-90%

response

Stool + DHUS

Supportive

(volume repletion)

TPE if severe acute

onset/neurologic

deficit

DIC

Search sepsis

or malignancy

Adapted from Clark WF, Sem Dial 2012

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Thrombotic Microangiopathy: Child

Adapted from Clark WF, Sem Dial 2012

Bloody diarrhea

Stool culture

E. coli O157: H7

No diarrhea

Test complement

D-HUS

Conservative

(volume repletion)

Infusion FFP (?)

a-HUS

TPE

Eculizumab

DIC

Test INR, PT, D-dimer

DIC

Search sepsis

or malignancy

TPE for TTP

ASFA Indication: category I

Rationale: TPE is superior to FFP infusions1,2

Replacement Fluid: FFP

Interval/duration:

TPE < 24 hours of presentation

1.0-1.5 plasma volume (60-75 ml/kg) daily

(platelets > 150x103; LDH normal)

Adjunctive therapy: corticosteroids(3)

Standard dose (1 mg/kg) > high dose (10 mg MPS/kg/day x3)

followed by 2.5 mg/kg/day (CR 53.4% vs 23.4%, p = 0.03)

(1) GA Rock; NEJM 1991

(2) M Michael, Cochrane Database Syst Rev 2009

(3) SJ Brunskill, Transf Med 2007

TTP: Response to Initial Therapy

Rapid response (1-2 days)

Non-focal neurologic symptoms

Moderate response (3-10 days)

Thrombocytopenia

Parameters of hemolysis

Slow response (weeks-months)

Anemia

Renal impairment (unpredictable, often

incomplete)

Treatment requires persistence and patience

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TTP: Follow-up and Outcome

Follow-up

Duration of initial treatment is undefined

Monitor blood cell count and LDH

Outcome

Relapse rates 29-82%

Chronic renal failure ( 25%)

Long-term neurologic effects (incidence?)

TTP: Relaps or Refractory Patients

Continue/intensify TPE

Rituximab(1)

Initial 375 mg/m²

Weekly (x4)

Splenectomy?

IVIG?

(1) S Jasti, J Clin Apher 2008; I de la Rubia,Transf Apher 2012

TPE for aHUS

ASFA indication:

Category I (factor H Ab)

Category II (complement factor gene mutations)

Rationale: no controlled trials, expert opinion(1)

Replacement fluid: FFP

Interval/duration:

1.0-1.5 plasma volumes daily

(platelets > 150 x 10³; LDH normal)

5x/week for two weeks

3x/week for two weeks

Subsequently according to evolution

Uncontrolled disease: eculizumab(2)

(1) C Loirat, Pediatr Nephrol 2008

(2) J Nürnberger, N Engl J Med 2009

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Diarrheal HUS: Treatment

Supportive care

FFP infusion: no significant benefit(1)

TPE: benefit in adults with severe acute

onset D-HUS(2)

(1) G Rizzoni, J Pediatr 1988

(2) E Colic, Lancet 2011

TPE in Anti-glomerular Basement

Membrane Disease

ASFA indication:

Serum creatinine < 500 µmol/l: category I

Diffuse alveolar hemorrhage (DAH) irrespective of serum creatinine: category I

Rationale for TPE:

Lower post therapy serum creatinine, lower incidence of ESRD, more rapid

decline of anti-GBM(1)

Less severe pulmonary hemorrhage(2)

Replacement fluid: albumin

(FFP 2–4 units last portion of exchange if DAH or kidney biopsy)

Interval/duration:

TPE 1.0-1.5 plasma volume daily/every other day minimum 14 days

Consider continuing TPE if serum creatinine & anti-GBM level not significantly

declined

Adjunctive therapy: corticosteroids, cyclophosphamide

(1) JB Levy, Ann Int Med 2001

(2) CO Savage, BMJ 1981

TPE in ANCA-associated Vasculitis

ASFA indication:

RPGN (Screat > 5.7 mg/dl); dialysis dependence(1)

: category I

Diffuse alveolar hemorrhage (DAH)(2)

: category I

Rationale for TPE: TPE is superior to IV MPS pulses in patients with

severe renal involvement:

renal recovery at 3 months: 69% vs 50%

progression to ESRD: 24% risk reduction

Replacement fluid: albumin

(FFP 2-4 U last portion of exchange if DAH or kidney biopsy)

Interval/duration

TPE 1.0-1.5 plasma volume

6-9 treatments over 2 weeks

Daily initially if concomitant anti-GBM

Adjunctive therapy: corticosteroids, cyclophosphamide

(1) D Jayne, JASN 2007

(2) PJ Klemmer, Am J Kidney Dis 2003

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TPE in Hyperviscosity Syndromes

ASFA indication: neurological symptoms (convulsions, coma)

in monoclonal gammopathies or cryoglobulinemia: category I

Rationale:

Prevalence hyperviscosity symptoms with 4 and 5 cp = 67%

and 75%(1)

One single TPE (1.0-1.5 plasma volume) reduces plasma

viscosity by 20-30%(2)

Replacement fluid: albumin (1/3)/saline (2/3)

Interval/duration:

Daily until acute symptoms abate (1-3 TPEs)

Maintenance 1 TPE every 1-4 weeks ( clinical symptoms)

Adjunctive therapy: chemotherapy

(1) BD Adams, Emerg Clin N Am 2009

(2) M Ballestri, 2007

TPE for Recurrence of Primary FSGS

ASFA indication: posttransplant recurrence of idiopathic FSGS:

category I

Rationale:

TPE + high dose cyclosporine: 75% remission(1)

Remission correlates with reduction of serum suPAR < 2000

pg/ml(2)

Replacement fluid: albumin or albumin/FFP

Interval/duration:

Daily for 3 days + 3 times/week for 2 weeks (minimum 9)

Tapering guided by degree of proteinuria

Adjunctive therapy: corticosteroids, cyclosporine, rituximab(?)

(1) ME Schachter, Clin Nephrol 2010

(2) C Wei, Nat Medicine 2011

TPE for Cryoglobulinemia

(1) EM Berkman, Transfusion 1980

(2) GE Russo, Transf Sci 1996

ASFA indication:

Severe organ damage (skin, kidney, neuropathy): category I

Cryocrit not to be used as criterion

Rationale:

No RCT

TPE associated with 70-80% clinical improvement(1,2)

Replacement fluid: albumin or plasma

Interval/duration:

1.0-1.5 plasma volume exchange every 1-3/days

Reevaluate after 8 procedures

Weekly/monthly according to symptoms

Warm room and warmed lines/replacement solutions

Adjunctive therapy: according to underlying disease

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TPE for Antibody Mediated Rejection (AMR)

ASFA indication: antibody mediated rejection: category I

Banff criteria 2001: (1) DSA; (2) allograft histology (PMN glomerular/peritubular);

(3) allograft IF (C4d peritubular capillaries)

Rationale:

TPE alone (removal DSA): no benefit in RCT(1)

Immunoadsorption: superior evidence(2)

TPE + IVIg (inhibition of residual DSA): 50-90% reversal of AMR and improved

graft survival (70-80%)(3)

Replacement fluid: albumin or albumin/saline

Interval/duration: no evidence based protocol

Set number of TPE, usually 5 or 6, daily or every other day

TPE procedures based on renal function, decrease in DSA

Low dose IVIg (0.1-0.4 g/kg) at end of each procedure

Adjunctive therapy: corticosteroids, MMF, rituximab, bortezomib

(1) HJ Gurland, Kidney Int Suppl 1983

(2) GA Bohmig, Am J Transplant 2007

(3) C Lefaucheur, Am J Transplant 2009

TPE IN NEUROLOGICAL DISEASES

TPE in neurological diseases

Guillain-Barré syndrome

Chronic inflammatory demyelinating

polyneuropathy (CIDP)

Myasthenia gravis

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TPE for Guillain-Barré Syndrome

ASFA indication: severe disease impairing independent walking or

requiring mechanical ventilation: category I

Rationale:

Anti-LOS/ganglioside antibodies

4 RCT: improvement in disability and ventilation need within 4

weeks(1-3)

Replacement fluid: albumin/saline

Interval/duration:

1.0-1.5 plasma volume every other day

5 to 6 procedures over 2 weeks

Alternative therapy: IVIG equally efficacious as TPE(4)

0.4 g/kg for 5 consecutive days

(1) M.Farkkila, Neurology 1987

(2) Guilliain Barré Study group, Neurology 1985

(3) French Cooperative Group on Plasma exchange in Guillain Barré Syndrome , Ann Neurol

1987 and 1997

(4) RA Hughes, Cochrane Syst Rev 2001

TPE for Chronic Inflammatory

Demyelinating Polyneuropathy (CIDP)

ASFA indication: short term treatment of CIDP: category I

Rationale:

Autoantibodies against proteins and glycolipids of peripheral nerves

2 RCT: improvement nerve conduction and neurologic-disability

score(1-2)

Replacement fluid: albumin/saline

Interval/duration:

1.0-1.5 plasma volume, 2 to 3 times/week until improvement

(4-6 weeks)

Taper as tolerated

Adjunctive therapy:

Corticosteroids, azathioprine, MMF, CsA

IVIG equally efficacious as TPE: 0,4 g/kg once a week, x 3

0,2 g/kg once a week, x 3

(1) PJ Duyck, NEJM 1986

(2) AF Hahn, Brain 1996

(3) PJ Duyck, Ann Neurol 1994

TPE for Myasthenia Gravis

ASFA indication: myasthenic crisis and pre-thymectomy: category I

Rationale:

Autoantibodies towards antigens in the postsynaptic membrane

(AChR: 80-90%; MuSK: 10%)

NO RCT

Replacement fluid: albumin/saline

Interval/duration:

1.0-1.5 plasma volume every other day

5 tot 6 procedures over 2 weeks

Adjunctive therapy:

Thymectomy, acetylcholinesterase inhibitor, corticosteroids,

azathioprine, MMF

IVIG equally efficacious as TPE(1)

:

0.4 g/kg/day on 3 to 5 consecutive days

(1) P Gadjos, Ann Neurol 1997

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COMPLICATIONS OF TPE

General Complications

Catheter-related

Thrombosis/hemorrhage; infection; pneumothorax

Anticoagulation-related

Bleeding risk

Pulmonary embolism if reinfused blood not properly anticoagulated

Oncotic pressure-related

Hypotension if hypo-oncotic fluid replacement

Pulmonary edema if serum protein much higher post TPE

Elimination of drugs

Drugs with high protein binding: antibiotics, anti-epileptic

drugs, diltiazem, thyroxin, cyclophosphamide, azathioprine

Biologicals: administer after TPE

Complications when substituting

albumin and/or saline

Depletion coagulopathy

1 plasma exchange: coagulation factors 60%; recovery 48 hours

Multiple treatments/week: pronounced depletion; recovery > 72

hours

if bleeding risk (Goodpasture, postbiopsy, …): substitute 2-4 FFP

Depletion of immunoglobulins

1 plasma exchange:serum Ig 60%; total body Ig stores 20%

Multiple treatments/concomittant IS: risk opportunistic infections

serum Ig < 500 mg/dl: IVIG 0.1-0.4 mg/kg

Hypokalemia

25% reduction in K+ post TPE (intravasal dilution)

history arrhythmia/digoxin use: add 4 mmol K+/liter albumin

5 % Albumin (Na+: 145 mmol/L; K+:

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Complications when substituting

albumin and/or saline

Hypocalcemia

Pyrogenic reactions

Anaphylactoid reactions

Flushing, hypotension, abdominal cramps in patients with

ACE-I

5 % Albumin (Na+: 145 mmol/L; K+:

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Potential Causes for Hypotension

during TPE

Cause Prevention/Treatment

Hypovolemia

Inadequate volume replacement; hypo-

oncotic fluids

• Slow removal of plasma

• Replace with 5% albumin, FFP,

colloid (60-80%) + saline (20-40%)

Anaphylaxis

Reaction to plasma components

Membrane bio-incompatibility

• Minimize FFP

• (Pre)treatment with antihistamines,

corticosteroids

Cardiac arrhythmia

Citrate-induced hypocalcemia

Hypokalemia (digitalis)

• Minimize FFP, slow infusion

• IV calcium prophylaxis

Bradykinin reactions • Avoid ACE-I

TRALI • Minimize FFP

Hemorrhage

Access-related

Anticoagulation, depletion coagulopathy

• Adequate anticoagulation

• Adequate FFP

Pulmonary embolus • Adequate anticoagulation

Adapted from Kaplan A, Seminars in Dialysis, 2012

References

Kaplan A. Am J Kidney Dis.

2008;52:1180-1196

Szczepiorkowski ZM, Winters JL.

J Clin Apher. 2010;25:83-177

Seminars in Dialysis. Vol. 25, Nr. 2

(March-April), 2012