Folie 1

1
Workshop - Blood Safety On the occasion of the
75th anniversary of Blood Service in Tomsk region
18.30 - 20.30 Procedures for virus
inactivation in donor blood Quality management
systems for blood banks and quality control of
blood safety testing German speakers/discussants
Igor W. Blau (Berlin), Christian Seidl
(Frankfurt a.M.), Wolfram H. Gerlich
(Giessen),Detlev H. Krueger (Berlin), Sigrid Nick
(Langen), Micha Nuebling (Langen), R. Stefan Ross
(Essen), Heinz Zeichhardt (Berlin)
2
Introduction - Transfusion Hazards Quality
Management of the Transfusion Process
Prof. Dr. med. Christian Seidl
3
Risk scale for major transfusion hazards
Serology NAT
Pre-Donation sampling / Pathogen Inactivation
Hospital quality system
Donor selection and/or Testing (HLA/HNA)
Irradiation
Modified from Dzik, W.H. in Brown F, Seitz R
Advances in Transfusion Safety 2001
4
Adverse events and errors Serious Hazards Of
Transfusion (SHOT)
ICBT Incorrect Blood Component Transfused
TTITransfusion Transmitted Infections
ATRAcute Transfusion Reaction DTRDelayed
Transfusion Reaction
5
Quality Management of the Transfusion Process
Clinical governance working group of the Ministry
of Health Arbeitskreis Blut (24 TFG)
The Vein to Vein Process
Transfusion law (Transfusionsgesetz TFG)
Guidelines Richtlinien (BÄK/PEI) 12 and 18
TFG state-of-the-art ,scientific and technical
medical content
GL 1.4.4 Chapter 4.
Hospital specific QMH 15 TFG Standard
procedures and recommendations Dienstanweisung
for transfusion practice
GL 1.4.3.6
Recommendations Leitlinien (BÄK) - Haemotherapy
with blood components and plasma derivates
6
Quality management system 15 TFG Hospital
based Transfusion Practice
Working Group Haemotherapy (regional)
Transfusion-Responsible Person (Quality
Management System)
Transfusion Commission (local)
Transfusion-Delegate(s) (for each
Department/Section)
Transfusing Physician(s)
Transfusion Recipient / Patient(s)
EU Optimal Use of Blood Use Project Working
Group Meeting 13th 17th August 2007
7
Quality management system 15 TFG Hospital
based Transfusion Practice

• Transfusion Commission (local board)
• Medical director
• Transfusion responsible Person
• Transfusion Delegates
• Pharmacist
• Director Nursing Department
• Director Technical Services

• Key responsibilities
• Implementation and consistency of legal
  requirements
• - Develop Hospital specific QMH 15 TFG
• Standard procedures and recommendations
• Dienstanweisung for transfusion practice
• based on Guidelines and Recommendations
• - Establish a link to the Pharmaceutical
  Commission
• Monitore the amount of blood used
• Training of physicians and nurses

Pocket Guide Transfusion Practice
EU Optimal Use of Blood Use Project Working
Group Meeting 13th 17th August 2007
8
Virus prevalence among blood donors
0,05
0,0003
0,01
0,01
9
Virus prevalence among blood donors
0,0003
0,001
0,001
0,0003
10
German Red Cross NAT Study
Virus NAT only Donations Ratio of
Incidence
positive (n) positives
per Mill.
HBV 43 30.956.260 1
719.913 1.4
HCV 22 31.094.964
11.413.407 0.71
HIV-1 8 30.921.353
13.865.169 0.26
Real Residual Risik before Introduction of NAT
GRC HIV-1 PCR kit
11
Contamination and Infectious Risk
Observed virale Infection risk
Bacterial Risk
Contamination 1 in 2.000
lt 1 in 500.000
HBV
lt 1 in 25 Millionen
HCV
Septic Reactions 1 in 100.000
1 in 25 Millionen
HIV
Death 1 in 250.000
including anti-HBc-testing since 2006 Result
of the German Red Cross observation study
1997-2005 for ELISA- and PCR-negative Blood
components from GRC blood establishments
Adapted from Blajchman MA, Trans Med Rev, 2004
18 11-24
12
(Re)Emerging Pathogens
1 VHF Viral Haemorrhagic Fever
2 HHV Humanes Herpes-Virus (adapted from
Woolhouse MEJ Trends Microbiol 2002)
13
Quality Control versus GERMS Study Results
Contamination Rate
Comparison of bacterial contamination rate of
pool versus apheresis platelet concetrates (PC)
Three different bacterial detection systems
(BacT/Alert, Pall eBDS and Scan system) in 50.000
PC (multicenter study)
Research Foundation of the German Red Cross Blood
Donor Services
14
What could be the solution ?
Platelet Products
Pathogen Inactivation
Testing
Rapid detection methods
Culture Methods
Photodynamic reactions
Photochemical reactions
BacT / ALERT
Pall eBDS
FACS
NAT
Scan-System
15
Problems of Bacterial Detection

• Method
• Sample size taken
• Time of sampling
• Incubation/bacterial culture
• Direct detection method
• All bacteria detected? / low level contamination
  relevance?
• No. of false negative results
• No. of false positive results
• Complex logistics of testing and information flow
• Recalls
• Already transfused products

16
Problem Sample Error
Bacteria
Patient
Sample drawn
?Testing Negative result
Sepsis / Death
17
Problem Incubation Time until Positive Signal in
BacTAlert
Number of products positive in BactT Alert
time (h)
18
Pathogen Inactivation
Modified from Klueter et al., 2004
19
Testing versus Inactivation

• unknown viruses
• leukocytes
• broad range of pathogens

• all products
• no additives

Testing
Inactivation

• unknown viruses
• restricted range of pathogens
• time dependent loss of activity
• costs dependent on number of
• pathogens tested

• no method for all products yet
• not effective against all pathogens
• (e.g. spec.viruses (only some methods)
• prions bacterial spores)
• loss of activity dependent on method
• increasing process costs

20
Milestones in the Development of Transfusion
Safety
Pathogen Inactivation
Molecular Biology
Testing for Markers of Infections
Safety Level
NAT / PCR
Immunohematology
e.g. HBsAg, HIV
e.g. Rhesus
Histocompatibility
AB0 System
1901 1940
1970 1997
2004
Adapted from Klueter et al., 2004
21
Acknowledgements
Institute Frankfurt Goethe University Hospital
of Frankfurt/Main Michael Schmidt Walid
Sireis Markus M. Müller Reinhard Henschler
22
Costs per quality adjusted life-year (QALY) per
100,000 PLT concentrates are estimated at
3,277,032 for BCU 18,582,844 for PRT The
relative cost effectiveness (CE) is estimated
at 3,596,256 (between BCU and PRT) ratio of
differences in costs and QALYs
Costs and benefits of bacterial culturing (BCU)
and pathogen reduction (PRT) in the Netherlands
Univariate sensitivity analysis

• Photochemical Reactions
• Psoralens
• Amotosalen-HCl (S-59, HelinxTM)
• Inactine (PEN-110)
• FRALE (S-303)

• Photodynamic Reactions
• Phenothiazine
• Methylene Blue
• Thionin
• Riboflavin

• Solvent Detergent Method (Pool Plasma only!)

Mart P. Janssen, Cees L. van der Poel, Erik
Buskens, Luc Bonneux, Gouke J. Bonsel, and Ben A.
van Hout, Transfusion, Vol. 46, June 2006