3/20/2013
1
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
3/20/2013
2
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
3/20/2013
3
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
3/20/2013
4
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
3/20/2013
5
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%
3/20/2013
6
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
3/20/2013
7
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.)
3/20/2013
8
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
3/20/2013
9
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
3/20/2013
10
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
3/20/2013
11
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
3/20/2013
12
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
3/20/2013
13
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
3/20/2013
14
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
3/20/2013
15
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
3/20/2013
16
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
3/20/2013
17
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
3/20/2013
18
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
3/20/2013
19
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
3/20/2013
20
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+: <2 mmol/l; Ca2+: 2-3 mg/dl; Citrate: 3 mmol/l
3/20/2013
21
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+: <2 mmol/l; Ca2+: 2-3 mg/dl; Citrate: 3 mmol/l
Complications when substituting FFP
Anaphylactic reactions (1.5-20%)
Symptoms: fever, urticaria, pruritus, wheezing, hypotension;
cardiopulmonary collapse rare
interrupt procedure, antihistamines, corticosteroids, epinephrine
if needed
pretreatment with antihistamines and/or corticosteroids
Citrate-induced hypocalcemia
Citrate infused as anticoagulant or contained in FFP (17.5 mmol/l)
Symptoms: perioral or distal extremity tingling; lightheadedness,
nausea, vomiting;
abdominal cramps, tetany, seizures; chest tightening;
arrhythmia ( QT) if Ca
2+
i < 35%
monitor Ca2+
i (30-60 min); prophylactic IV calcium
Complications when substituting FFP
Citrate-induced metabolic alcalosis
Citrate HCO3: accumulation in renal failure
if TPE and dialysis required same day: TPE first
Transfusion-related lung injury (TRALI)
Leucoagglutination in pulmonary circulation (HLA/leucocyte
donor Ab)
Symptoms: dyspnea, cyanosis (non cardiogenic pulmonary
edema), hypotension
3/20/2013
22
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
