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Quality Control
And
Pathogen Inactivation of Platelets
Ohood Al.Ayyadhi
Laboratory Manager
Blood Transfusion services
Kuwait Central Blood Bank
Pathogen Inactivation
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Introduction.
Why Pathogen Inactivation.
Methods.
Kuwait Central Blood Bank Results.
Infectious Risks
Transfusion of biological fluids
=
Viruses, Parasites, Bacteria, Prions, ???
Infectious Risks
Test
Known
vs
Risk
Unknown
Pathogens of highest concern
in the Middle East
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West Nile virus
SARS
Vaccinia
Chikungunya virus
Dengue
Avian flu virus (H5N1)
Borrelia burgdorferi
Trypanosoma cruzi
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Plasmodium falciparum
Leishmania
Babesia microti
HIV
HBV
HCV
HTLV
Bacterial Contamination
Kuwait Central Blood Bank
What’s our Scope?
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The ONLY Central Blood Bank
21 Government Hospitals
20 Private Hospitals
2 Military Hospitals
Blood product supplier to Allied armies
What’s our Scope?
• 69,000 Whole blood donations.
• 100% Leukocyte Reduced RBC & Plasma.
• 7,794 Apheresis Platelets (55,000 units).
What’s our Scope?
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AABB Accredited 1989.
CAP Survey 1994.
Accredited by the National Quality Program.
National Reference Laboratory.
Accredited as regional reference center for
Arabian countries.
• AABB Immunohaematology Reference Lab IRL
self assessment 2008.
What’s our Scope?
• Training center for post-graduate
hematologist.
• Training center for pre-graduate medical lab
technologist.
• Training center for regional countries.
• Therapeutic Apharesis Center.
• National Antenatal screening program.
Pathogens of highest concern in the
Middle East (KCBB)
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Bacterial Contamination.
HBV.
HCV.
HIV.
Viral Infectious Risks At KCBB
Infectious Risks at KCBB
HIV
2008
Total Tests 61771
2009
60991
2010
62720
2011
68239
Anti-HIV
4 (0.06%) 1 (0.01%) 0 (0.00%) 4(0.006%)
NAT-HIV
4
2
3
2
Infectious Risks at KCBB
HBV
2008
Total Tests 31771
2009
60991
2010
62720
2011
68239
HBsAg
191(0.31%) 163(0.27%) 163(0.26%)
122(0.19%)
NAT-HBV
139
157
175
59
ANTI-HBC 6059(9.8%) 6187(10%) 5657(9%)
5715 (8.76%)
ANTI-HBs 3979(65%) 3754(60%) 3753(5.98%) 3950 (6.06%)
Infectious Risks at KCBB
HCV
2008
2009
2010
2011
Total Tests
61771
60991
62720
68239
Anti-HCV
317 (0.19%)
208 (0.34%)
163 (0.26%)
110 (0.17%)
NAT-HCV
115
122
53
76
Infectious Risks at KCBB
HTLV
2008
Total Tests 31771
2009
60991
2010
65218
2011
68239
Anti-HTLV 14 (0.02%) 8 (0.01%) 12 (0.019%) 9 (0.012%)
Infectious Risks at KCBB
MALARIA
2008
2009
11319
2010
10830
2011
8207
Total Tests
11218
AntiMalaria
183 (3%) 239 (2.1%) 220 (2.03%) 728 (8.87%)
Bacterial Contamination Risks
of Platelets At Kuwait Central Blood Bank
Comparison of Residual Risks
1:100
Transmission risk,
per unit
HIV
1:1000
Bacterial
Contamination
(platelets)
1:10 000
HBV
HCV
Septic 1:100 000
Fatalities
(platelets)
1:1 000 000
1984
1986
1988
1990
1992
1994
1996
Updated from: Goodnough LT e t al. NEJM 1999;341:126-7
1998
2000
2002
Bacterial Contamination Risks
Unit Transfused
Red Blood Cells
Platelet pheresis units
TOTAL, all units
Risk per Million Units
Confirmed Report of
Fatality
Bacterial Contamination
6.0
1.0
32
7.1
7.4
1.1
Perez P et al. Transfusion 1999;39:2S.
Bacterial Contamination Risks
Unit Transfused
Red Blood Cells
Platelet pheresis units
TOTAL, all units
Risk per Million Units
Confirmed Report of
Fatality
Bacterial Contamination
6.0
1.0
32
7.1
7.4
1.1
1/140,800
Perez P et al. Transfusion 1999;39:2S.
Bacterial Contamination Risks
Unit Transfused
Red Blood Cells
Platelet pheresis units
TOTAL, all units
1/31,000
Risk per Million Units
Confirmed Report of
Fatality
Bacterial Contamination
6.0
1.0
32
7.1
7.4
1.1
1/140,800
Perez P et al. Transfusion 1999;39:2S.
Frequency of Contamination
Based on Johns Hopkins’ Data
Post-transfusion sepsis
Fatalities
Plt Conc
402/million
62/million
SDP
75/million
14/million
Ness PM et al. Transfusion 2001;41:857-61.
Recalculation: LJ Dumont.
Frequency of Contamination
Based on Johns Hopkins’ Data
Post-transfusion sepsis
Fatalities
Plt Conc
402/million
62/million
SDP
75/million
14/million
Compare:
HIV
HCV
0.33/million
1/million
Ness PM et al. Transfusion 2001;41:857-61.
Recalculation: LJ Dumont.
Bacterial Contamination
AABB STD 5.1.5.1
The blood bank or transfusion services shall have methods to
limit and detect bacterial contamination in all platelet
components.
History of testing in KCBB
Test
Date
Syphilis
1965
HBVs-Ag
1970
HIV-Ab
1985
Malaria-Ab
1987
HBVc-Ab
1992
HBVs-Ab
1992
HCV-Ab
1992
HTLV-I&II Ab
1994
HIV-I & II Ab
1997
HIV-Ag
1997
Bacterial Detection
2005
NAT- HIV, HCV, HBV
2006
Bacterial Risk at KCBB
• 6,800 Apheresis Platelets (~ 40,000 units).
• 0.5 – 1 confirmed cases of sepsis per year.
Bacterial Detection
• Scansystem
•March 05 – May 07
•26,000 units
•eBDS Pall
•June 07 – May 08
•14,000 units
•10% of collection tested by culture as QC
Bacterial Detection
Summary results of QC of platelet aphaeresis component
(10% collection)
Detection System
Tested
Initial
Components Positive
False
Positive
False
Negative
Scansystem
2475
March 05 – May 07
5 (.20%)
5 (.20%)
1 (.04%)
eBDS
June 07 – May 08
1292
2 (.15%)
2 (.15%)
1 (.07%)
Total
3767
(22,602)
7 (.19%)
7 (.19%)
2 (.05%)
Mitigation
• Delay of component release (2 days)
• Complexity of procedures
• Results:
–False positives (0.2 %)
–False negatives (0.05%)
• Safety?:
–Did not prevent all septic transfusion reactions
–Did change the risks of bacterial contamination.
Pathogen Inactivation
WHY ?
Why is Pathogen Inactivation
Important?
• Reduced risk of bacterially contaminated platelet
transfusion
• Further closing of window period for screened viruses
• Added protection against untested pathogens (e.g.
Chagas)
• Pro-active protection against emerging pathogens (e.g.
Chikungunya, West Nile)
• Possible reduction in adverse transfusion events
• Potential to revisit donor deferral strategies and
enlarge donor pool
• Public expectation of ‘ZERO risk’
Pathogen Inactivation
Systems
Platelet Pathogen Inactivation Systems
• Intercept
– Amotosalen + UV
Platelet Pathogen Inactivation Systems
• Intercept
• Mirasol
– Riboflavin + UV
Platelet Pathogen Inactivation Systems
• Intercept
• Mirasol
• Theraflex UV
Intercept
Blood System for
Platelets
Mechanism of Action
UVA Illumination
Amotosalen
DNA or RNA
of pathogen
Intercalation
Crosslinking
Amatosalen Cross links Both Single
and Double Stranded Nucleic Acids
Helical
Regions
Double-stranded
DNA or RNA
Single-stranded
DNA or RNA
INTERCEPT Blood System for
Platelets
Integrated Processing Set
1
2
Collection Amotosalen
UVA Illumination Device
3
Illumination
4
CAD
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Storage
Mirasol® Pathogen Reduction
Technology System
Mirasol PRT System Overview
• The Mirasol PRT System uses riboflavin (vitamin B2)
and UV light to inactivate pathogens, altering their
nucleic acids so they cannot replicate.
Mechanism of Action
UV light + riboflavin: irreversible inactivation
• Riboflavin molecules form complexes
with nucleic acids
• UV light from the Mirasol Illuminator
activates the riboflavin molecule in the
complex
• Photoactivated riboflavin induces a
chemical alteration to the functional
groups (such as guanine bases) of
nucleic acids making pathogens unable
to replicate
Mirasol PRT System Concept
+
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Platelet or
Plasma product
Riboflavin
(Vitamin B2)
solution
UV Light
• Reduction of viruses, bacteria, parasites
• Inactivation of residual white cell
Theraflex UV
System
Theraflex
Theraflex
• Methylen Blue and UV illumination device
used as a technique for Pathogen Reduction
KCBB
Clinical Experience with
Platelet PI
Pathogen Inactivation
(INTERCEPT) Implementation
• Training, March 2008
• Validation, May 2008
• 100 % Pathogen Inactivation of Platelets
replaced 1st May 2008
• AABB inspection 15th May 2008
KCBB Results
Source
• Trima Accel version 5.2 / 6.0
• Hemonetics (MCS+) 998 CF-E
KCBB Results
Collection dose
• Single dose (3-4 x 1011/unit)
• Double dose (6-7 x 1011/unit)
• Baby units (0.5 x 1010/unit)
KCBB Results
Source
KCBB Results
Collection dose
• Single dose
(3-4 x 1011/unit)
• Double dose
(6-7 x 1011/unit)
• Baby units
(5 x 1010/unit)
Double
Single
KCBB QC Results
Parameters:
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Volume (Pre & Post)
Platelet Count (Pre & Post)
Count Loss
Culture
KCBB QC Results
QC Samples:
• Total
• Valid
990 (15.3%)
718 (11.1%)
KCBB QC Results
• Total: 718
• 66 % of tested units ≥ 3 x 1011/unit
• 34 % < 3 x 1011/unit
– Pre-PI is < 3 x 1011/unit
– Divided as baby units.
• Pathogen Inactivation process has no
significant effect on the final product.
KCBB QC Average Results
Parameter
July-August
2008
August-September
2008
Pre Platelet Count
3.25
3.8
Post Platelet
Count
3.05
3.2
Loss
0.21
0.6
All Culture NEGATIVE
KCBB QC Average Results
All Culture NEGATIVE
INTERCEPT Pathogen Inactivation Workflow
Duration
Time
zero
Action
Aphaeresis PLT
Collection tools
Sealer
Computer
Filtration
Processing
Average time = 3-6min
Average time 2hr
Random Donation
Equipment
Registration
02:00
02:15
Filtration
Filtration Stands
Clamps
Sealers
Connection device
Computer
Scales
Intercept set (LV/SV)
Average time =6-16hr
Average time =6min
02:20
02:30
Illumination
Storage
CAD start
08:30
Final Platelets
End Product:
leucocytes reduce aphaeresis
platelet pathogen inactivation
Collection
Trima: Resting time 1hr
Haemonitic: no need for resting
Print label
Process
Incubator
Scales
Clamps
Sealers
Computer
RAD-SURE (UVA illumination indicator)
Present Testing
Test
Syphilis
HBVs-Ag
HIV-Ab
Malaria-Ab
HBVc-Ab
HBVs-Ab
HCV-Ab
HTLV-I&II Ab
HIV-I & II Ab
HIV-Ag
NAT- HIV, HCV, HBV
Bacterial Detection
Date
1965
1970
1985
1987
1992
1992
1992
1994
1997
1997
2005
2006
Present Testing
Test
Syphilis
HBVs-Ag
HIV-Ab
Malaria-Ab
HBVc-Ab
HBVs-Ab
HCV-Ab
HTLV-I&II Ab
HIV-I & II Ab
HIV-Ag
NAT- HIV, HCV, HBV
Bacterial Detection
Date
1965
1970
1985
1987
1992
1992
1992
1994
1997
1997
2006
REMOVED 2008
Present Testing Processing
Test
Date
Syphilis
1965
HBVs-Ag
1970
HIV-Ab
1985
Malaria-Ab
1987
HBVc-Ab
1992
HBVs-Ab
1992
HCV-Ab
1992
HTLV-I&II Ab
1994
HIV-I & II Ab
1997
HIV-Ag
1997
NAT- HIV, HCV, HBV
2006
Bacterial Detection
REMOVED 2008
Pathogen Inactivation
2008
Clinical Effectiveness
Processing effects
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Platelet count loss.
Platelet activation.
Frequent platelet transfusion.
Compromised CCI.
Processing effects
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Same day release of Platelets.
Simple procedure.
No bacterial contamination.
Less allo-immunization.
Cost
• Expensive.
Cost
• Less expensive than:
– Bacterial testing.
Cost Effectiveness at KCBB
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Better platelet products quality on TIME.
STOP Bacterial detection tests.
STOP Irradiation.
STOP Malaria testing.
Platelets Pathogen Inactivation
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Conclusion
PI highly prevalence agent.
PI vs. Testing; compromised budgeting.
PI in highly endemic areas.
Acknowledgment
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Dr. Reem Al.Radwan
Dr. Nabeel Sanad
Suhaila Al.Shatty
Samiya Al.Hamdan
Badriya Al.Radwan
Hanan Sheshtari
Ghadeer Ashkanani
Maryam Ameer
• Ghadeer Boland
• Quality Control Lab
• Quality Managment
Department
• IT Department
• Platelets Donation
Department
www.atmckw.com