Quality Control And
Pathogen Inactivation of Platelets
Ohood Al.AyyadhiLaboratory ManagerBlood Transfusion servicesKuwait Central Blood Bank
Pathogen Inactivation
• Introduction.• Why Pathogen Inactivation.• Methods.• Kuwait Central Blood Bank Results.
Infectious Risks
Transfusion of biological fluids=
Viruses, Parasites, Bacteria, Prions, ???
Infectious Risks
Test
vs
Risk
Known Unknown
Pathogens of highest concern in the Middle East
• West Nile virus• SARS• Vaccinia• Chikungunya virus• Dengue• Avian flu virus (H5N1)• Borrelia burgdorferi• Trypanosoma cruzi
• Plasmodium falciparum• Leishmania • Babesia microti• HIV• HBV• HCV• HTLV• Bacterial Contamination
Kuwait Central Blood Bank
What’s our Scope?
• The ONLY Central Blood Bank• 21 Government Hospitals• 20 Private Hospitals• 2 Military Hospitals• Blood product supplier to Allied armies
• 69,000 Whole blood donations.• 100% Leukocyte Reduced RBC & Plasma.• 7,794 Apheresis Platelets (55,000 units).
What’s our Scope?
• 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.
What’s our Scope?
Pathogens of highest concern in the Middle East (KCBB)
• Bacterial Contamination.• HBV.• HCV.• HIV.
Viral Infectious Risks At KCBB
2011 2010 2009 2008 HIV
68239 62720 60991 61771 Total Tests
4(0.006%)0
(0.00%)1
(0.01%)4
(0.06%) Anti-HIV
2 3 2 4 NAT-HIV
Infectious Risks at KCBB
2011 2010 2009 2008 HBV
68239 62720 60991 31771 Total Tests
122(0.19%) 163(0.26%)163(0.27
%)191(0.31
%) HBsAg
157 59 175 139 NAT-HBV
5715 (8.76%) 5657(9%)
6187(10%)
6059(9.8%) ANTI-HBC
3950 (6.06%)
3753(5.98%)
3754(60%)
3979(65%) ANTI-HBs
Infectious Risks at KCBB
2011 2010 2009 2008 HCV
68239 62720 60991 61771 Total Tests
110( 0.17%) 163( 0.26%) 208( 0.34%) 317( 0.19%) Anti-HCV
76 53 122 115 NAT-HCV
Infectious Risks at KCBB
2011 2010 2009 2008 HTLV
68239 65218 60991 31771 Total Tests
9 (0.012%)
12 (0.019%)
8 (0.01%)
14 (0.02%) Anti-HTLV
Infectious Risks at KCBB
2011 2010 2009 2008 MALARIA
8207 10830 11319 11218 Total Tests
728 (8.87%) 220 (2.03%) 239 (2.1%) 183 (3%) Anti-Malaria
Infectious Risks at KCBB
Bacterial Contamination Risksof Platelets At Kuwait Central Blood
Bank
HIV
HBVHCV
1996199419921990198819861984
1:100
1:1000
1:10 000
1:100 000
1:1 000 000
1998 2000
Transmission risk, per unit
Updated from: Goodnough LT e t al. NEJM 1999;341:126-7
Comparison of Residual Risks
2002
BacterialContamination
(platelets)
SepticFatalities(platelets)
Unit Transfused Risk per Million Units Confirmed Report of FatalityBacterial Contamination
Red Blood Cells 6.0 1.0Platelet pheresis units 32 7.1TOTAL, all units 7.4 1.1
Perez P et al. Transfusion 1999;39:2S.
Bacterial Contamination Risks
Perez P et al. Transfusion 1999;39:2S.
1/140,800
Unit Transfused Risk per Million Units Confirmed Report of FatalityBacterial Contamination
Red Blood Cells 6.0 1.0Platelet pheresis units 32 7.1TOTAL, all units 7.4 1.1
Bacterial Contamination Risks
1/140,800
Unit Transfused Risk per Million Units Confirmed Report of FatalityBacterial Contamination
Red Blood Cells 6.0 1.0Platelet pheresis units 32 7.1TOTAL, all units 7.4 1.1
1/31,000
Bacterial Contamination Risks
Perez P et al. Transfusion 1999;39:2S.
Frequency of Contamination
Ness PM et al. Transfusion 2001;41:857-61.Recalculation: LJ Dumont.
Plt Conc SDPPost-transfusion sepsis 402/million 75/millionFatalities 62/million 14/million
Based on Johns Hopkins’ Data
Compare:HIV 0.33/millionHCV 1/million
Ness PM et al. Transfusion 2001;41:857-61.Recalculation: LJ Dumont.
Frequency of Contamination
Plt Conc SDPPost-transfusion sepsis 402/million 75/millionFatalities 62/million 14/million
Based on Johns Hopkins’ Data
Bacterial ContaminationAABB 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 KCBBTest Date
Syphilis 1965HBVs-Ag 1970HIV-Ab 1985Malaria-Ab 1987HBVc-Ab 1992HBVs-Ab 1992HCV-Ab 1992HTLV-I&II Ab 1994HIV-I & II Ab 1997HIV-Ag 1997Bacterial Detection 2005NAT- 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
Summary results of QC of platelet aphaeresis component (10% collection)Detection System Tested
ComponentsInitial Positive
False Positive
False Negative
ScansystemMarch 05 – May 07
2475 5 (.20%) 5 (.20%) 1 (.04%)
eBDSJune 07 – May 08
1292 2 (.15%) 2 (.15%) 1 (.07%)
Total 3767(22,602)
7 (.19%) 7 (.19%) 2 (.05%)
Bacterial Detection
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 InactivationWHY ?
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 InactivationSystems
Platelet Pathogen Inactivation Systems
• Intercept– Amotosalen + UV
• Intercept • Mirasol
– Riboflavin + UV
Platelet Pathogen Inactivation Systems
• Intercept• Mirasol• Theraflex UV
Platelet Pathogen Inactivation Systems
InterceptBlood System for
Platelets
DNA or RNAof pathogen
Mechanism of Action
Amotosalen
Intercalation Crosslinking
UVA Illumination
Double-strandedDNA or RNA
Single-strandedDNA or RNA
Helical Regions
Amatosalen Cross links Both Single and Double Stranded Nucleic Acids
INTERCEPT Blood System for Platelets
UVA Illumination Device
Integrated Processing Set
1Collection
2Amotosalen
3Illumination
4CAD
5Storage
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
• Reduction of viruses, bacteria, parasites• Inactivation of residual white cell
+Riboflavin
(Vitamin B2)solution
UV LightPlatelet or
Plasma product
+
Mirasol PRT System Concept
Theraflex UVSystem
Theraflex
• Methylen Blue and UV illumination device used as a technique for Pathogen Reduction
Theraflex
KCBBClinical 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
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)
DoubleSingle
KCBB Results
KCBB QC Results
Parameters:• Volume (Pre & Post)• Platelet Count (Pre & Post)• Count Loss• Culture
QC Samples:
• Total 990 (15.3%)• Valid 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 Results
KCBB QC Average Results
Parameter July-August2008
Pre Platelet Count 3.25
Post Platelet Count 3.05
Loss 0.21
August-September2008
3.8
3.2
0.6
All Culture NEGATIVE
KCBB QC Average Results
All Culture NEGATIVE
Collection Storage
Average time 2hr
Registration
Action
Duration
Process
Equip-ment
Random Donation
zero 02:00 02:15Time
Trim
a: R
estin
g tim
e 1h
rH
aem
oniti
c: n
o ne
ed fo
r res
ting
Prin
t lab
el
Aphaeresis PLT Collection toolsSealerComputer
IncubatorScalesClampsSealersComputer RAD-SURE (UVA illumination indicator)
Filtration StandsClampsSealersConnection deviceComputerScalesIntercept set (LV/SV)
End
Prod
uct:
leuc
ocyt
es re
duce
aph
aere
sis
plat
elet
pat
hoge
n in
activ
ation
Filtration
Filtration
Processing
Final Platelets
02:20
Illumination
02:30 08:30
Average time =6min Average time =6-16hrAverage time = 3-6min
CAD start
INTERCEPT Pathogen Inactivation Workflow
Present TestingTest Date
Syphilis 1965HBVs-Ag 1970HIV-Ab 1985Malaria-Ab 1987HBVc-Ab 1992HBVs-Ab 1992HCV-Ab 1992HTLV-I&II Ab 1994HIV-I & II Ab 1997HIV-Ag 1997NAT- HIV, HCV, HBV 2005Bacterial Detection 2006
Present TestingTest Date
Syphilis 1965HBVs-Ag 1970HIV-Ab 1985Malaria-Ab 1987HBVc-Ab 1992HBVs-Ab 1992HCV-Ab 1992HTLV-I&II Ab 1994HIV-I & II Ab 1997HIV-Ag 1997NAT- HIV, HCV, HBV 2006Bacterial Detection REMOVED 2008
Present Testing ProcessingTest Date
Syphilis 1965HBVs-Ag 1970HIV-Ab 1985Malaria-Ab 1987HBVc-Ab 1992HBVs-Ab 1992HCV-Ab 1992HTLV-I&II Ab 1994HIV-I & II Ab 1997HIV-Ag 1997NAT- HIV, HCV, HBV 2006Bacterial Detection REMOVED 2008
Pathogen Inactivation 2008
Clinical Effectiveness
• Platelet count loss.• Platelet activation.• Frequent platelet transfusion.• Compromised CCI.
Processing effects
Processing effects
• 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
• Better platelet products quality on TIME.• STOP Bacterial detection tests.• STOP Irradiation.• STOP Malaria testing.
Platelets Pathogen Inactivation
• Conclusion • PI highly prevalence agent.• PI vs. Testing; compromised budgeting.• PI in highly endemic areas.
Acknowledgment
• 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
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