Plasma Exchange
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Transcript Plasma Exchange
Critical Care Combined
Conference
R4 李建霖 / VS 吳允升
2013/08/29
Patient Profile
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Age: 52 y/o
Sex: female
Marital status: married
Occupation: housekeeper
Smoking: nil
Alcohol: nil
Family History
Brief History
2006/07
2006/08
• Dyspnea 馬偕 UCG: pulmonary HTN
Refer to Dr. 曾春典’s OPD
• Cardiac cath: MPA: 50mmHg, PAWP:
10mmHg
• Chest CT: Compatible with primary
pulmonary hypertension. No evidence
of pulmonary embolism.
• NO, high flow O2 & Viagra test: only
partial response
Brief History
2006/08
• CV OPD medication:
– Viagra, Coumadin and Bosentan
2008/10
• UCG: ↑ pulmonary HTN
– TRPG: 98.4mmHg
2012/10
• Cardiac cath: MPA: 57mmHg
• Remodulin use
Present Illness
• Progressive dyspnea
2013/02/28 • 為恭 hospital:
2013/02/27
– Desaturation + hypotension intubation
– VT Cardioversion x 1
ED of NTUH
– VT Cardioversion x 2
CCU admission
Treatment Course
2013/02/28
• Persistent hypoxia (SpO2~85%) under
FiO2 1.0
– UCG: LVEF: 78.3%, TRPG: 70.6mmHg
– Cashed epoprostenol + iNO
• VA ECMO
2013/03/04 • Central VA ECMO
2013/03/01
Central VA ECMO
Treatment Course
2013/02/28
• Persistent hypoxia (SpO2~85%) under
FiO2 1.0
– UCG: LVEF: 78.3%, TRPG: 70.6mmHg
– Cashed epoprostenol + iNO
• VA ECMO
2013/03/04 • Central VA ECMO
2013/03/01
– Improved daily activity under central VA
ECMO (吃飯,看電視…)
Wait for lung transplantation
Treatment Course
• Bleeding tendency under ECMO use
• GI bleeding + wound bleeding
massive blood transfusion
2013/06/01 • First donor: cross match positive
• Flow-PRA:
• Class I: 100%
• Class II: 99.78%
2013/02/28
Treatment Course
2013/06/26
• 2nd donor: still cross match positive
• Consult Dr.蔡孟昆 for positive flow PRA
• Desensitization protocol
Desensitization Protocol
• Indication: 術前PRA > 74%, Virtual cross
match (+)
• OR: 術中3次的plasma exchange
– 1) 5% albumin
• BW x 80 x (1 – HCT%) ≈ total plasma volume (TPV)
• Albumin volume = TPV x 0.05
• Albumin bottle = albumin volume / 10
– 2) 5% albumin
– 3) FFP exchange
Desensitization Protocol
• ICU:
– 當日: Simulect 20mg in N/S 50mL run 30 mins
– POD1: FFP exchange
– POD2: FFP exchange
– POD3: 75% FFP + 25% albumin
– POD4: Simulect 20mg in N/S 50mL run 30 mins
– POD5: 50% FFP + 50% albumin
– POD6: IVIG (2g/kg, Total volume / 2~3 days / 24
hours)
Results of Cross Match
4°C T cell
4°C B cell
37°C T cell
37°C B cell
6/01
1:8 positive
1:4 positive
1:4 positive
> 1:8
positive
6/26
1:32 positive 1:32 positive
1:32 positive 1:32 positive
7/07
1:32 positive 1:32 positive
1:32 positive 1:32 positive
Desensitization
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7/07 Plasma exchange x 3 during OP
7/08 Plasma exchange + Simulect
7/09 Plasma exchange
7/10 Plasma exchange
7/11 Simulect + IVIG (24-hour drip)
7/13 DFPP (2A)
7/14 IVIG
7/15 Rituximab
Panel Reactive Antibody
Class I (%)
Class II (%)
3/04
65.50
42.11
6/04
100
99.78
7/08
100
82.04
7/15
99.82
99.06
Discussion
Desensitization in
Lung Transplantation
Methods for Antibody Screening
AMR, antibody-mediated rejection; CDC, complement-dependent lymphocytotoxicity; ELISA, enzyme-linked
immunosorbent assay; FC, flow cytometry; HAR, hyperacute rejection; SAB, single-antigen beads; SPI, solidphase immunoassays; vXM, virtual crossmatch; XM, crossmatch.
• The comparative sensitivities are LUM > ELISA/FC > CDC
Transplantation 2013;95: 19~47
Kidney International(2011) 79, 583 – 586.
Pretransplant Panel Reactive
Antibodies in Lung Transplantation
1987~2005 USA
10236 lung transplant
Ann Thorac Surg 2008; 85: 1919–24
Pretransplant Panel Reactive
Antibodies in Lung Transplantation
Ann Thorac Surg 2008; 85: 1919–24
Pretransplant Panel Reactive
Antibodies in Lung Transplantation
Ann Thorac Surg 2008; 85: 1919–24
Pretransplant Panel Reactive
Antibodies in Lung Transplantation
Ann Thorac Surg 2008; 85: 1919–24
Pretransplant Panel Reactive
Antibodies in Lung Transplantation
Ann Thorac Surg 2008; 85: 1919–24
Preexisting HLA Antibodies in Lung
Transplantation
Transplantation 2013;95: 19~47
Pretransplantation
Donor-Specific Antibodies
Transplantation 2013;95: 761~765
Desensitization Therapies
J Heart Lung Transplant 2010;29:914 –956
Plasma Exchange in Desensitization
• A single exchange of 1.0 PV removes ~63% of
all solutes in the plasma
– An exchange of 1.5 PV removes ~78%
• In case of slowly forming antibodies, 5
separate treatments during a 7- to 10-day
period will be required to remove 90% of the
patients’ initial total-body burden
Transfus Med Hemother 2012;39:234–240
Plasma Exchange in Desensitization
• TPE should be repeated daily for a minimum
of 3 days
– 5–7 days
– Until the circulating antibodies are reduced to
very low titer
• The effect appears to be long lasting
– No return of DSA observed in patients followed for
an average of 13 months
Transfus Med Hemother 2012;39:234–240
Plasmapheresis + IVIG
Therapeutic Apheresis (1997) 1(2):147-151
Plasmapheresis + IVIG
• Plasmapheresis was begun as soon as possible
after notification that a suitable organ was
available and accepted
– 1 session, 1.5 plasma volume
– 5% albumin + 4U FFP
• Immediately after plasmapheresis 20 g of
5% IVIG
Therapeutic Apheresis (1997) 1(2):147-151
Peritransplant IVIG &
Extracorporeal Immunoadsorption
• January 1992 ~ July 2003
• Duke University Medical Center, Durham, NC,
USA
Human Immunology 66, 378 –386 (2005)
Peritransplant IVIG &
Extracorporeal Immunoadsorption
• An averaged median of 83.5 days
(3rd-party)
Human Immunology 66, 378 –386 (2005)
Peritransplant IVIG &
Extracorporeal Immunoadsorption
P = 0.32
(23)
(12)
(345)
Human Immunology 66, 378 –386 (2005)
P = 0.05
P = 0.03
Human Immunology 66, 378 –386 (2005)
Therapeutic apheresis in lung
transplantation in Jena
2008 ~ 2012
Atherosclerosis Supplements 14 (2013) 33-38
Therapeutic apheresis in lung
transplantation in Jena
• 3 consecutive days
– When necessary, every second or third day after
that until graft functionality was established or the
graft was lost
• Average 1.3 times the plasma volume
• Replacement fluid:
– Early postoperative phase: therapeutic plasma
– Later: 1:1 mix of Octaplas LG and 5% human
albumin
Atherosclerosis Supplements 14 (2013) 33-38
Donor-specific HLA Antibodies
Following Plasma Exchange Therapy
St. Louis Children’s Hospital from 2007 to 2010
• A cycle of TPE: daily for 5 days using 1.5-volume exchanges
• Replacement fluid: 5% albumin
– Risk of bleeding: FFP
J. Clin. Apheresis 28:301–308, 2013
Donor-specific HLA Antibodies
Following Plasma Exchange Therapy
J. Clin. Apheresis 28:301–308, 2013
Donor-specific HLA Antibodies
Following Plasma Exchange Therapy
P = 0.02
P = 0.58
J. Clin. Apheresis 28:301–308, 2013
Therapeutic strategies antibodymediated rejection
Guidelines for Heart Transplant
• A PRA 10% indicates significant allosensitization
• Desensitization therapy should be considered when the
calculated PRA is considered by the individual transplant
center to be high enough to significantly decrease the
likelihood for a compatible donor match or to decrease the
likelihood of donor heart rejection where unavoidable
mismatches occur
– Average threshold PRA level for initiation of treatment: 35%
(range 10 –100%)
• Choices to consider as desensitization therapies include IV
immunoglobulin (Ig) infusion, plasmapheresis, either alone
or combined, rituximab, and in very selected cases,
splenectomy
J Heart Lung Transplant 2009;28:213–25
J Heart Lung Transplant 2010;29:914 –956
Desensitization Protocol in NTUH
• Indication: 術前PRA > 74%, Virtual cross
match (+)
• OR: 術中3次的plasma exchange
– 1) 5% albumin
• BW x 80 x (1 – HCT%) ≈ total plasma volume (TPV)
• Albumin volume = TPV x 0.05
• Albumin bottle = albumin volume / 10
– 2) 5% albumin
– 3) FFP exchange
Desensitization Protocol in NTUH
• ICU:
– 當日: Simulect 20mg in N/S 50mL run 30 mins
– POD1: FFP exchange
– POD2: FFP exchange
– POD3: 75% FFP + 25% albumin
– POD4: Simulect 20mg in N/S 50mL run 30 mins
– POD5: 50% FFP + 50% albumin
– POD6: IVIG (2g/kg, Total volume / 2~3 days / 24
hours)
•58008C血漿置換術(支付點數2475點)
Plasma exchange:限下列病患實施
SLE,CNS involvement
Myasthenia gravis crisis
Macroglobulinaemia
RPGN
Goodpasture's disease
Multiple myeloma
Guillain-Barre syndrome
Thrombocytopenic purpura
Multiple sclerosis and neuromyelitis optica
其他經專案向保險人申請同意實施者
•58016C二重過濾血漿置換療法(支付點數2475點)
•Double filtration plasmapheresis:施行本項之適應症請依支付標準
58008C「血漿置換術」之規定辦理。
全民健保醫療費用支付查詢網站: http://www.nhi.gov.tw/query/query2_list.aspx
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Centrifugal Device
(MCS+)
Membrane apheresis
KM8800
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KPS8800
HF400
Transfus Apher Sci. 2005 Apr;32(2):209-20
J Clin Apher. 2010;25(5):240-9
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Membrane
apheresis
Advantages
Disadvantages
Fast and efficient
plasmapheresis
No citrate requirements
Can be adapted for
cascade filtration
Removal of substances limited by
sieving coefficient of membrane
Unable to perform cytapheresis
Requires high blood flows, central
venous access
Requires heparin anticoagulation,
limiting use in bleeding disorders
Centrifugal Capable of performing
cytapheresis
devices
Expensive
Requires citrate anticoagulation
No heparin requirement Loss of platelets
More efficient removal
of all plasma components
Brenner: Brenner and Rector's The Kidney, 8th ed
56
Portion of Plasma Volume
Volumea
Exchanged
Exchanged (Ve/Vp) (Ve, mL)
Immunoglobulin or
Other Substance
Removed (MRR, %)
0.5
1,400
39
1.0
2,800
63
1.5
4,200
78
2.0
5,600
86
2.5
7,000
92
3.0
8,400
95
aPlasma volume = 2,800 mL in a 70-kg patient, assuming
hematocrit = 45%.
Ve, volume of plasma exchanged; Vp, estimated plasma
volume; MRR, macromolecule reduction ratio.
Handbook of Dialysis
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Experience from a heart transplantation case at NTUH
Solumedrol 500mg
IVIg 15g (heart lung machine)
Bortezomib (Velcade) IV slow push
IVIg 30g slowing infusion
Solumedrol 500mg + Rituximab (Mabthera) IV drip
RATG + FK506
TIW
D-9
D-7
D-5
D-3
D-1 OP day D1
D3
D5
1.5 PV 1.5 PV 1.5 PV 1.5 PV 1.5 PV 1.5 PV 2 PV 1.5 PV 1.5 PV 1.5 PV
DFPP DFPP DFPP DFPP DFPP
DFPP TPE DFPP DFPP DFPP
IVIg IVIg IVIg
IVIg IVIg
(OR)
Initial Ab X(1-78%)5
=0.0005 initial amount
residual Ab X(1-86%)
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J Clin Apheresis 2010;25:83-177
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Traffic
Accident
Transfer
to NTUH
Cardiac echo:
LVEF 19%
8/14 8/15 8/16
8/23
VV-ECMO
LM dissection
s/p POBAS
Desaturation
PCWP 40 mmHg
Dilate LV
8/31 9/1
9/5 9/6
Extubation
9/15
LV Drain
Cardiac cath:
No ISRS
10/5
LV Assist Device
Remove
VV-ECMO
10/20
10/25
檢查項目
數值
37℃
B cell
1:32 Positive Negative
37℃
T cell
1:32 Positive Negative
4℃
B cell
1:32 Positive Negative
4℃
T cell
1:32 Positive Negative
Donor:楊XX
數值
1:32 Positive
1:32 Positive
1:32 Positive
說明
37℃
37℃
4℃
檢查項目
B cell
T cell
B cell
4℃
T cell
1:32 Positive Negative
11/3
Panel reactive antibody:
Anti-HLA class I: 61%
Anti-HLA class II: 72%
標準值
標準值
Negative
Negative
Negative
說明
Donor:鄭XX
Rituximab (Mabthera)
200 mg
Bortezomib (Velcade)
3.5 mg
Solu-Medrol
1000 mg
Intravenous immunoglobulin
45 gm
R-anti-thymocyte globulin
25 mg
Plasma Exchange
Hypotension, Bradycardia
11/3
11/4
11/6
11/8
11/10
11/12
Donor
11/12
檢查項目
數值
標準值
37℃
B cell
1:8 Positive Negative
4℃
T cell
1:2 Positive Negative
說明
Double Filtration Plasmapheresis
37℃ T cell
1:2 Positive Negative
3L/session, 1.2x plasma volume
4℃
B cell
1:4 Positive Negative
total 5 course
Donor:侍XX
Isoproterenol
Millisrol
Dopamine
Primacor (Milrinone)
Bosmin
3000
Graft failure ?
2500
CO: 2.23
CI: 1.48
2000
1500
1000
CVVH
500
11/11
11/12
Transplant
11/13
11/14
DFPP
11/15
11/16
Massive bloody
pleural effusion
DFPP
IVIG
11/17
IVIG
Solu-Medrol
FK506
Cellcept
11/18
11/19
PT
PTT
sec
sec
26.6
39.1
• Definition
• Exposure of the immune system to antigen (transplant
organ) sufficient to generate an immune response
• Antibody
– ABO
– Anti-HLA
– Non-HLA
• Blood transfusions
• Pregnancy
• Previous organ transplant
• Placement of a ventricular device
Approximate 30% incidence of antibody production (PRA > 10%)
after LVAD placement
J Heart Lung Transplant 2002; 21: 1218-24
Prevent rejection
Humoral Response
Donor selection
Recipient
Desensitization
Cellular Response
Immunosuppressive
agents
Human Immunology 2005;66:334-42
Examples of desensitization
J Heart Lung Transplant 2009;28:213-25
Pre-heart transplant plasmaheresis for
sensitized patients (high PRA)
• 1.5 plasma volume
plasmapheresis + 20g 5%
IVIG, then heart transplant
• 1.5 plasma volume
plasmapheresis qod
(followed by 20g 5% IVIG )X
5 sessions. Then a single
plasmaphereis with IVIG at
the time of surgery
J Heart Lung Transplant 1999;18:701 Clin
Transplant 2006;20:476-84
HLA class I
HLA class II
Clin Transplant
2006;20:476-84
Clin Transplant
2006: 20: 476–484
On-pump TPE for XM heart transplant
• High blood flow and thus increased pheresis
rate to shorten treatment time than standard
setting of TPE/DFPP
• 3 plasma volume within 60-90min
• Especially need to watch out [Ca]
J Extra Corpor Technol 1999;31:177-83 J
Heart Lung Transplant 2008;27:1036-9
Comparative long-term outcome
5-year patient survival
1-year rejection-free survival
523 heart transplant, 95 PRA>10%, 21/95 desensitization, 74 untreated
Survival: no significant difference
Rejection: significant decrease in desensitized patients
(Treated with PP+IVIG+Rituximab)
Clin Transplant. 2010 Oct 25
Proposed protocol for
desensitization
Solumedrol 500mg
IVIG 15g (heart lung machine)
Bortezomib (Velcade) IV slow push
IVIG 30g slowing infusion
Solumedrol 500mg + Rituximab (Mabthera) IV drip
RATG + FK506
TIW
D-9
D-7
D-5
D-3
D-1 OP day D1
D3
D5
1.5 PV 1.5 PV 1.5 PV 1.5 PV 1.5 PV 1.5 PV 2 PV 1.5 PV 1.5 PV 1.5 PV
DFPP DFPP DFPP DFPP DFPP
DFPP TPE DFPP DFPP DFPP
(OR)
IVIG IVIG IVIG IVIG IVIG
Initial Ab X(1-78%)5
=0.0005 initial amount
residual Ab X(1-86%)
Extracorporeal photopheresis
T-cell
B-Cell
Primary prophylaxis
N Engl J Med 1998;339:1744-51
Clin Transplantation 2000;14:162-6
Secondary prophylaxis
J Heart Lung Transplant 2006;25:283-8
Extracorporeal photopheresis
(ECP)
• Leukapheresis-based immunomodulatory therapy.
• Mechanism:
– causes apoptosis of the treated and abnormal T cells
– induces monocytes to differentiate into dendritic cells
capable of phagocytosing and processing the apoptotic Tcell antigens
– may cause a systemic cytotoxic CD8+ T-lymphocyte–
mediated immune response to the processed apoptotic Tcell antigens
– induce antigen-specific regulatory T cells, which may lead
to suppression of allograft rejection or GVHD
Thank You!