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A summary review provided by the

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FDA-Approved for Q.C. purposes only on Leukoreduced Apheresis Platelets ... 3,927 apheresis units cultured (5 mL into aerobic bottle, BacT/Alert automated system) ... – PowerPoint PPT presentation

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Title: A summary review provided by the


1
Bacterial Contamination in Blood ProductsRisks,
Prevention and Detection
  • A summary review provided by the
  • American Red Cross Blood Services Regions
  • serving the North Atlantic Area
  • July, 2003

2
Bacterial Contamination
in Blood Products
  • Agenda
  • What is the Problem?
  • What are the Risks?
  • What Organisms are Associated with Bacterial
    Contamination?
  • What are the Sources of Contamination?
  • What Corrective Actions are Planned?

3
Recent Advances in Testing Technology1990-2003
  • Anti-HCV (1990)
  • Multi-antigen anti-HCV (1992)
  • Anti-HIV1/2, replacing anti-HIV-1 (1992)
  • HIV-1 p24 antigen (1996)
  • HCV/HIV NAT (IND) (1999)
  • Licensed NAT (2003)
  • West Nile Virus (IND) (2003)

4
Comparison of Residual Risks
1100
Transmission risk, per unit
HIV
11000
Bacterial Contamination (platelets)
HBV
110 000
Clinical Sepsis (platelets)
HCV
Septic Fatalities (platelets)
1100 000
11 000 000
1996
1994
1992
1990
1988
1986
1984
1998
2000
2002
Updated from Goodnough LT e t al. NEJM
1999341126-7
5
Bacterial Contamination of
Blood Products
  • First recognized infectious risk of blood
    transfusion
  • Risk greatly reduced in the 1960s by the use of
    closed, sterile systems for the collection and
    storage of blood
  • Recent dramatic improvements in safety from viral
    screening and testing have reduced the risks from
    Hepatitis and HIV
  • Bacterial sepsis is now the most common
    infectious disease event following transfusion

6
Bacterial Contamination of Blood Products
  • Bacterial contamination occurs primarily in
    room-temperature stored products (platelets) but
    can occur in red blood cells and plasma also
  • The blood banking community is taking steps to
    improve prevention and detection of bacterial
    contamination
  • The American Association of Blood Banks, as well
    as the College of American Pathologists have
    established compliance criteria for transfusion
    services

7
Bacterial Contamination in Blood Products
  • The American Association of Blood Banks has
    issued two new standards (March, 2003)
  • 5.1.5.1 The blood bank or transfusion service
    shall have methods to limit and detect bacterial
    contamination in all platelet components.
  • 5.1.5.1.1 Standard 5.1.5.1 shall be implemented
    by March 1, 2004
  • 5.6.2 The venipuncture site shall be prepared so
    as to minimize the risk of bacterial
    contamination. Green soap shall not be used

8
Bacterial Contamination in
Blood Products
  • College of American Pathologists Accreditation
    Checklist (December, 2002)
  • TRM.44955 Phase 1 Does the laboratory have a
    system to detect the presence of bacteria in
    platelet components?

9
Bacterial Contamination of
Blood Products
  • What are the Risks?

10
Risk of clinical sepsis
Pooling issues
  • Ness et al, Transfusion 200141857-60.
  • Identified clinical cases of transfusion
    associated sepsis over a 12 year period, with
    conversion from 51.7 random donor platelets to
    99.4 SDPs
  • The donors/septic event remained constant at
    15,000 throughout the 12 year period, despite the
    conversion to SDPs
  • Pooled random donor platelets were 5.5-times more
    likely to cause sepsis than SDPs due to pool size

11
Bacterial Contamination of Blood Products
  • What Bacterial Organisms are associated with
    Blood Product Contamination?

12
Bacterial species in platelets implicated in
clinical sepsis
Compilation of data from Clin Micro Rev 1994
7290-302 Transfusion 2001411493-99
www.shot.demon.co.uk/toc
n 86
13
Bacterial species in platelets implicated in
septic fatalities reported to the FDA (1976-1998)
n 52
14
Differences between the species implicated in
septic morbidity and mortality in platelet
components
  • S. epidermidis is less commonly observed in
    septic fatalities and more commonly observed in
    septic reactions
  • Klebsiella is commonly observed in septic
    fatalities
  • Gram negative organisms are implicated in more
    fatalities (60) than gram positive organisms
    (40) gram positives cause a majority of septic
    reactions (56)

15
Organisms implicated in sepsis
from platelets
  • Approximately 30 are associated with normal skin
    flora
  • Approximately 56 are gram positive
  • All are aerobic or facultative anaerobes
  • A rare (single case) exception Clostridium
    perfringens fatality from a pooled platelet unit
    Trans Med 1998819-22

16
Bacterial Contamination in Blood Products
  • What are the Sources of Bacterial Contamination?

17
Sources of Bacterial Contamination
  • Skin Surface Contamination
  • Phlebotomy Core
  • Donor Bacteremia
  • Containers and Disposables
  • Environment

18
Skin source
Avoiding Skin Contamination
  • Diversion of the initial blood flow
  • Improvement in pre-phlebotomy skin cleansing

19
Diversion of initial blood flow
  • Diversion of initial blood flow into sampling
    tubes
  • Reduces the load of skin-associated bacteria
    entering blood container
  • Phlebotomy core directed into sampling pouch
    instead of blood container

20
Clinical data supporting diversion of initial
blood flow
  • de Korte et al. Vox Sang 20028313-16
  • Collected blood normally or diverted the first
    10mL of whole blood into a satellite bag
  • Performed bacterial testing by automated blood
    culture (BacT/Alert) in a laminar flow hood

21
Skin disinfection methods
  • Some agents may reduce the number of surface
    bacteria more than others
  • Method of application and applicator may have
    some impact on the extent of reduction of surface
    bacteria
  • Minimum scrub of 30 seconds required to be
    effective

22
Impact of Skin Disinfection on surface bacteria
63
Goldman et al, Transfusion 199737309-12
23
Recurrent contamination from the dimpled skin of
one plateletpheresis donor
  • Anderson et al., Am J Med 1986405-11.
  • One donor gave 17 plateletpheresis donations from
    a scarred dimpled site in the right antecubital
    fossa
  • Two units were implicated in septic events traced
    to this donor
  • Four units, including the two units linked to the
    septic event, were culture positive with
    coagulase negative Staphylococcus
  • Follow up blood samples obtained from the
    non-scarred left antecubital fossa were routinely
    culture negative

24
Recurrent contamination from an asymptomatic
bacteremic donor
Donor bacteremia
  • Rhame et al., Ann Intern Med 197378633-41.
  • One plateletpheresis donor was linked to 7 cases
    of Salmonella cholerae-suis transfusion
    associated bacterial sepsis 2 cases were fatal
  • Three of the cases were linked to positive
    culture of the platelet units
  • The donor had a low-grade bacteremia and
    unknowingly had Salmonella osteomyelitis of the
    tibia

25
Multiple cases of sepsis from
contaminated blood containers
Container source
  • Heltberg et al. Transfusion 199333221-7
  • Högman et al. Transfusion 199333189-91.
  • Serratia marcescens was cultured from three
    septic patients and their implicated units in
    Denmark
  • All units were collected using the same lot of
    blood containers
  • 11 of 1,515 blood products collected using the
    implicated lot were positive for Serratia
    marcescens
  • An organism of the same ribotype was isolated
    from the manufacturing plant
  • The same containers were implicated in Sweden

26
A fatal case of Clostridium perfringens sepsis
from a platelet pool
Environmental source
  • McDonald et al., Transfusion Medicine
    1998819-22.
  • C. Perfringens is a spore forming facultative
    anaerobe, found in soil and human intestinal
    tract
  • Organism recovered from platelet pool septic
    recipient was on antibiotics no organism
    recovered
  • Patients death was considered a septic event
  • The same serotype of Clostridium was isolated
    from the arm of 1 of the 4 donors a subsequent
    culture of the same arm 6 months later yielded
    fecal flora
  • The donor was a mother who carried her two
    toddlers in the crook of her arm

27
Bacterial Contamination in
Blood Products
  • What Options exist to Prevent and Detect
    Bacterial Contamination?

28
Bacterial Contamination of PlateletsPrevention
and Detection Options
  • Donor screening not feasible except for arm
    screening. Cant detect asymptomatic bacteremic
    donors
  • Arm Preparation-Limited effectiveness of arm
    scrub
  • Pathogen reduction not yet available. May not
    inactivate spore forming organisms
  • Better phlebotomy methods and initial blood
    diversion
  • Bacterial detection offers best confirmatory
    option

29
Bacterial Detection Options in Platelet Products
  • Visual examination for discoloration, clumping or
    abnormal morphology
  • Microscopy
  • Gram stain
  • Acridine orange
  • Measuring Biochemical changes
  • Lowered pH
  • Reduced Glucose
  • Bacterial culture
  • Detection through oxygen consumption
  • Detection through CO2 production

30
Bacterial Detection Options in Platelet Products
  • Visual Examination
  • Inspect product prior to transfusion for
    discoloration or abnormal clumping
  • Perform swirl procedure to detect morphologic
    changes in platelets
  • Normal shaped platelets will align with fluid
    flow and shimmer when swirled
  • Contaminated platelets, among others, lose
    discoid shape and do not shimmer when swirled
    Not a specific marker for contamination

31
Swirling
Alignment with flow
SENSITIVITY 75 SPECIFICITY 95
No alignment with flow
Low pH Metabolic disturbance
Leach MF et al. Vox Sang 199874(suppl 1)1180.
32
Bacterial Detection Options in Platelet Products
  • Microscopic Methods
  • Gram Stain or Acridine Orange preferred methods
  • Limitations
  • Must be performed by the Transfusion Service
    prior to product issue for transfusion
  • Lack sensitivity with low bacterial load

33
Bacterial Detection Options in
Platelet Products
  • Measuring Biochemical Changes
  • Measure changes in glucose consumption against a
    control. Variances of gt2 S.D. may indicate
    bacterial contamination
  • Dipstick testing
  • Limitations
  • Both this method and staining methods are
    subjective, require high levels of contamination,
    and must be performed prior to issue by the
    Transfusion Service

34
Detecting Bacteria in Platelets Biochemical
Changes
Glucose, Day 0
-2 SD
Storage Time, d
after Burstain JM et al. Transfusion
199737255-8.
35
Chemical Tests - Dipsticks
Must be performed immediately before issue
because of its relative insensitivity and the
need for high bacterial counts
36
Bacterial Detection Options in Platelet Products
  • Blood Culture Methods
  • Two methodologies presently approved by FDA for
    Quality Control use
  • bioMeriuex BacT/Alert System
  • Pall Biomedical BDS System

37
Bacterial Detection Options in Platelet Products
  • bioMeriuex BacT/Alert System
  • Detects bacterial growth in culture bottles by
    measuring CO2 production
  • Automated reader continuously monitors samples
  • Sampling interval of gt24 hours post phlebotomy
  • Culturing interval of gt24 hours post sampling
    (aerobic and anaerobic cultures)
  • Cultures incubate for 5-7 days may identify
    positive cultures post-transfusion
  • FDA-Approved for Q.C. purposes only on
    Leukoreduced Apheresis Platelets

38
Practical Application of Culturing in a
Transfusion Service Laboratory Aubuchon, Dartmouth
Experience in first 3 years 3,927 apheresis
units cultured (5 mL into aerobic bottle,
BacT/Alert automated system) 23 initial
positives (0.5) in 28 h (10-69) 14 not
confirmed on repeat culture 5 not able to be
recultured 4 confirmed positives
RATE 1/1,000 units (95 CI to 1/600)
39
Detecting Bacteria in Platelets Detection of
Growth by O2 Consumption Pall BDS system
Measure O2 in headspace
24 h
Limit 19.5
Filter Stops WBCsPlts Passes Bacteria
24 h at 35C
Gas impermeable bag
40
Bacterial Detection Options in Platelet Products
  • Pall Biomedical BDS System
  • Detects bacterial contamination by measuring O2
    consumption
  • Automated reader measures O2 levels in headspace
    of culture pouch
  • Sampling interval of gt24-48 hours
  • Culture performed for gt24-30 hours
  • FDA-Approved for Q.C. on leukoreduced platelet
    concentrates and leukoreduced apheresis platelets

41
Bacterial Detection Options in Platelet Products
  • Limitations of Blood Culture Methods
  • Early sampling/testing may not detect small
    bacteria per bag. Approved methods require 24-30
    hour wait before sampling
  • Two FDA-Approved methods require bacteria to grow
    up after sampling to detectable levels, so
    culture must be done well before planned
    transfusion (Blood Center)
  • The two time intervals (collection to sampling
    and sampling to release/transfusion) dominate the
    logistic considerations

42
Bacterial Detection Options in Platelet Products
  • Limitations of Blood Culture Methods
  • Both options require leukoreduced platelets
  • BacT/Alert requires continued culture after
    product release
  • Release and recall (BacT/ALERT) or hold to end of
    culture to release (PALL BDS)

43
Bacterial Detection Options in Platelet Products
  • Limitations of Blood Culture Methods
  • Need to balance the risk of platelet shortages
    versus the risk of platelet contamination
  • The two available devices are FDA-Approved for
    Q.C, and not approved as pre-release tests
  • Cost
  • Probable negative impact on outdates
  • Possible extension of platelet storage to seven
    days or pooling/storing whole blood derived
    platelets

44
Bacterial Contamination in Transfusable Blood
Products
  • AABB Guidance
  • Association Bulletin 03-07 issued May 16, 2003
  • Provides guidance for methods to limit
    contamination and to detect contamination

45
AABB Association Bulletin 03-07May 16, 2003
  • Methods to Limit Contamination
  • Careful phlebotomy No green soap prep
  • Iodine based scrub recommended
  • Consider phlebotomy diversion sample first
    technologies
  • Consider increased use of apheresis platelets

46
AABB Association Bulletin 03-07May 16, 2003
  • Methods to Detect Contamination
  • Culture methods optimal. Two approved products
    cited. Other culture methods can be validated. No
    label claims allowed
  • Due to insensitivity, staining and dipstick
    methods should be used as close in time to issue
    as possible
  • Validation of all methods is required
  • Swirl procedure useful for inspection but does
    not by itself meet AABB Standard 5.1.5.1

47
Bacterial Contamination in Blood Products
  • American Red Cross Bacterial Prevention and
    Detection Strategy
  • Implement prevention and detection strategies to
    meet the requirements and timelines of the AABB
    and CAP
  • Solicit customer feedback to develop efficient
    and cost-effective implementation strategies
  • Keep customers well-informed during the
    pre-implementation period
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