Transcript Blood Transfusion 1

Blood Transfusion
Dr Emer Lawlor, IBTS
3rd February 2003
First Blood Transfusions
1628
Harvey
Discovered Circulation of Blood
1665-’66
Wilkins & Lower
Transfusions from dog to dog
1667
Jean-Baptiste Denis
Performed first recorded blood
transfusions from animals to humans
19th Century Transfusions
1818
James Blundell, Obstetrician
First transfusion of human
to human
Early transfusion: Paris, France
20th Century Transfusions
1901
Karl Landsteiner
Discovers A, B, O Blood
Groups
20th Century Transfusions
1902
AB Group discovered
1907
Importance of crossmatching blood between
donor & recipient
1914
Sodium Citrate proposed as anticoagulant
1936
First Blood Bank: Barcelona, Spanish Civil War
1940
Levine & Landsteiner, Rhesus blood Group
System
Bad Blood
France, Switzerland, Italy, Netherlands,
Germany, Denmark, Ireland,
Australia, New Zealand,
Canada, USA
Japan
Aims of Transfusion Centre
• Provision of Blood of the best possible
quality and safety for the patient
receiving it
• To care for the donor - ensure act of
donation does not harm donor
Blood Supply Chain
• Blood Donor Screening Criteria
• Donation Process
• Donation Testing
• Component preparation
• Plasma Products
Donor Screening
• Self deferral of ‘At Risk’ groups
• Health Questionnaire
• Microbiological screening of each
donation
Blood Donor Criteria
• Age 17-65 ( new donors until 60)
• Weight > 50kg ( 7st 12Ibs)
• General health
• Specific illnesses
• Contact with infection
Blood Donor Criteria
• HIV,Hepatitis risk
• Medication
• CJD
• Hb > 13 M; >12 F
Haemoglobin Testing
Alternatives to Voluntary
Donors: Autologous
•5-10% of patients are fit to predeposit
autologous blood
•Orthopaedic, Plastic Surgery, Gynaecology
•Up to 5 units can be predeposited/1 week
•Increased donor reactions
•Still have risk of : Clerical error, Bacterial
Infections
Alternatives to Voluntary
Donors: Directed
• Relatives or friends
• Not demonstrably safer
• Not voluntary
• Viral marker rates higher as often first time
donors
• TA-GVHD
Blood Donation
• 475mls Blood + 63mls anticoagulant
Red Cells
Plasma
Buffy Coat
Platelets
• Red Cells + Optimal Additive Solution
Saline
Adenine
Glucose
Mannitol
• Expiry date 35 days
SAGM
Blood Components and
Products
Blood Component Production
Blood Component Production
Leucodepletion
• Universal leucodepletion introduced in
1999 to reduce the risk of vCJD
transmission by blood
• other benefits - less febrile reactions,
less alloimmunisation, less GVHD, ?
reduce immunosuppresssive effects
Leucodepletion
Platelets
• Pools prepared from buffycoats of
whole blood donations (4 donations)• Apheresis concentrates from one donor
using a cell separator
• pool/apheresis pack (250mls) =
standard adult dose
Blood Donation Testing
• Microbiology markers
• Blood grouping and screening for high
titre antibodies
• Quality monitoring
O
A
B
ABO Groups
Cells
Serum
A
Anti B
B
Anti A
AB
-
O
Anti AB
Frequency of ABO & Rh(D)
Groups in Ireland
•Group O
56%
•Group A
31%
•Group B
11%
•Group AB
2.5%
•Rh (D) positive
85%
•Rh (D) negative
15%
ABO Grouping
Patient Red Cells
PT 1
PT 2
PT 3
PT 4
+
-
+
-
B
-
+
+
-
Anti AB
+
+
+
-
A
B
AB
O
Anti A
Test Anti
Reagents
Cells v Serum
Serum v Cells
Microbiology testing
• Current
–
–
–
–
–
–
–
–
–
anti HIV 1+2
HIV PCR
HBsag
HBc assay
anti HCV
HCV PCR
anti HTLV1/2
syphilis
anti CMV
• Future
– Bacterial culture of
components
– Prions
Hospital Blood Transfusion
Laboratory
Patient/donor testing and product
selection and issue
Tests prior to transfusion
IBTS
Hospital
•ABO & Rh typing
Donor
Patient
•Antibody screen
Donor
•ABO & Rh typing
•Antibody screen
Compatibility Test (x-match)
Donor red cells + patients serum
Saline and LISS Coombs
Antigens on Red Cells
Blood Group Antibodies
1.
Naturally occurring:
- ABO
- Anti-Hi, P1, E
Immune
2.
Pregnancy:
- Rhesus, Kell, Fya + Others
3.
Transfusion:
- Rh, Kell, Fy, JKa + Others
Conventional Testing.
Weak reactions often difficult to interpret. Can also be
downgraded due to shaking the completed test.
Principle of Gel Technology
• The sephadex gel matrix acts as a sieve.
• Large agglutinates remain on or near the top
of the gel interface.
• Smaller agglutinates pass partway through
the gel, depending on size.
• Unagglutinated cells pass to the base of the
microtube
ABO/Rh Typing
Group B
RhD
positive
Antibody Screening
Positive antibody screen.
Antibody could cause a transfusion reaction or
affect an unborn baby.
Purpose of Crossmatch
• Detect unsuspected ABO incompatibility
Donor centre
Error in laboratory
• Detection of unsuspected antibodies in
<1% cases
Crossmatching
ABO Group Crossmatch
Donor and
patient
compatible.
Unit safe to
transfuse.
Patient B
Positive
Recipient Serum
Donor Red Cells
Electronic Crossmatch
• Donor units
• Repeat ABO Rh groups performed on
all donor units
• Automated Grouping
• Validated computer software to ensure
that ABO incompatible units cannot be
selected for patient
Blood Component Storage
• Whole blood/red cells - 2-6C for up to 35
days use within 5 hours of removal from
blood fridge
• Platelets -20-24C on agitator for 5 days
• SD Fresh frozen plasma ( FFP) for 6
months - use within 4 hrs of thawing
• Cryoprecipitate -30C use within 4 hours
of thawing
Haemovigilance
Looping the Loop
Safety of the Transfusion Chain
from Vein to Vein
Right
Blood
+
Right
Patient
+
Right
Time
=

Transfusion Chain
• Supply from Transfusion Centre
•
•
•
•
•
•
•
•
•
Patient and sample identification
Transport of sample to laboratory
Laboratory ordering/testing process
Storage
Delivery of blood unit to patient
Administration
Monitoring
Adverse Reaction reporting
Guidelines, Audit and Review (outside loop)
Transfusion Chain
Hospital
•patient & sample
Identification
Transfusion
Centre
•Blood Supplied
Laboratory
•Ordering
•Testing
•Storage
Patient
•Blood Administered
•Monitored
Haemovigilance
•Adverse Reaction
reporting
•Guidelines, Audit
& review
NHO Incidents (category)
1999-2001
70
60
50
40
1999
2000
2001
2002
30
20
10
TT
I
DH
TR
TR
AL
I
Un
usu
al
AU
TO
TA
CO
ST
R
AH
O
AA
IB
C
T
0
Transfusion Chain
• Supply from Transfusion Centre
•
•
•
•
•
•
•
•
•
Patient and sample identification
Transport of sample to laboratory
Laboratory ordering/testing process
Storage
Delivery of blood unit to patient
Administration
Monitoring
Adverse Reaction reporting
Guidelines, Audit and Review
IBCT (n=31)
‘Site of First Error’
6.5%(2)
6.5%(2)
10%(3)
29%(9)
16%(5)
Prescription &/or
Request
Hosp Blood Bank
Administration
Site of Collection
32%(10)
Sampling
Unclear
Wrong
Pre-Transfusion Samples
 2 cases in the first two years of NHO reporting
 NHO audit 2000: 40% samples not labelled at
bedside as per guidelines or prelabelled
 Untoward incident reports St Elsewhere’s 2000
 8 wrong patient samples bled
 samples out of hours
 non phlebotomy staff
 prelabelled tubes
 musical beds
Near Misses only because lab had historic group on patient!
Wrong ABO Group - Case 1
 Pre transfusion sample was taken from
wrong patient.
 Patient received an ABO incompatible
transfusion.
 Transfusion reaction investigations led
to the identification of multiple errors.
NHO Report, 2001
Wrong ABO Group (Cases 5 & 6)
• Two patients in the same ward, one Group
O, other Group A, received blood
crossmatched for each other
– Remote checking of units
– Failure to positively identify the patients
– Error detected by nursing staff following
commencement of the transfusion.
– Transfusion reaction in O patient who
received 100mls A red cells
NHO Report, 2001
Immediate Haemolytic
Transfusion Reactions
IgM
Anti A
A antigen
Complement Activated C1-9
Intravascular
Haemolysis
Causes of error in deaths due to
haemolytic reactions
• Blood given to wrong person
49%
• Breach of identification procedures
– sample taken from wrong person
– given to person with same surname
– given to roommate
• Blood Bank errors 29%
– Identification errors
– Wrong blood issued
– Serological errors 13%
The Final Check
How Good is It ?
• 20 of 31 cases (ie.64.5%) the bedside
checking procedure failed.
• May not detect errors
– of sampling
– in the transfusion laboratory
Accident waiting to happen?
Reported incidents
1/600,000 fatalities
1/30,000 ABO incompatible
transfusions
1/12,000 incorrect units
administered
Near-Miss Events
????????
Kaplan & Battles 2001
Estimates of the risk of
post-transfusion complications
(US Figures)
Risk of
occurrence
1/100
HIV
HCV
HBV
1/1,000
1/100,000
1:600,000 <---Fatal acute hemolytic reaction
1999
1998
1997
1996
1995
1994
1993
1992
1991
1990
1989
1988
1987
1986
1985
1984
1983
1/1,000,000
Immediate Hazards of Blood
Transfusion
• Simple Febrile reactions
• Allergic or anaphylactoid reactions
• ABO incompatibility leading to acute
hemolysis
• Septic shock due to bacterial contamination
• Transfusion Associated Circulatory Overload
• Transfusion Related Acute Lung injury
Immediate complications
(1-6 h)
• Immunological
–
–
–
–
Febrile, non-haemolytic
Allergic /Anaphylactic
Haemolytic transfusion reaction
Transfusion Related Acute Lung Injury (TRALI)
• Non-Immunological
–
–
–
–
Congestive Cardiac Failure
Bacterial Contamination
Haemolysis-heat damage, freezing, hypotonic fluids
Embolism
Febrile Nonhaemolytic
Transfusion Reactions (FNHTR)
• Definition: ~1oC rise in temperature and/or chills
• Incidence 0.5% per unit transfused
• Alloimmunisation to HLA antigens-pregnancy, previous
transfusion
• Cytokine generation during component storage e.g.
platelets
• Bacterial contamination of blood component
• Importance:
– differentiate from ABO, HTR
– possibility of sepsis from infected unit:
» platelet 1:7,000
» red cells 1:33,000
Urticarial Reactions
• 1-3% of transfusions
• Slow/Stop the transfusion rate
• Administer iv antibodies e.g chlorpheniramine
10-20 mg
• If no further progression after 30 mins
transfusion may proceed normally
• Prevention: prophylactic antihistamines
Delayed Hazards
• Delayed Hemolytic Transfusion Reactions
• Post Transfusion Purpura
• Transfusion Associated Graft versus Host
Disease
• Viral infection - parasitic infections ?prions
• Immunosuppression
• Iron overload in multi- transfused recipients
Frequency of Transfusion
Adverse Events
Transfusion Associated
Circulatory Overload
TRALI
ABO incompatible transfusion
Severe Anaphylactoid reaction
GVHD/Post Transfusion Purpura
Bacterial infection Red Cells Platelets
Viral infection in Ireland - HIV
- HCV
- HBV
1:200
1:5,000
1;30,000-60,000
1:20,000
1:750,000 to 1:1mill
1:7,000
1:3.3 million
1:1 million
1:500,000
Transfusion Associated
Circulatory Overload (TACO)
• 1% of transfusions are complicated by TACO
• dysnoea, hypertension, crepitations,O2 sats
• Risk of volume overload/respiratory distress
especially in the small and/or elderly patient
• Largely avoidable by careful attention to fluid
balance
Transfusion Related Acute
Lung Injury
• 3rd commonest cause of death from transfusion
• 89% associated with Granulocyte antibodies or
HLA antibodies in donor
• Donor antibodies react with patient white cells
• Aggregates in lungs
• Neutrophil priming by lipid ? Older components
• 2 Hit hypothesis-underlying condition ?
haematological malignancy, ?cardiac
CXR - 21/11/01
CXR - 24/11/01
Graft versus Host Disease
• Rarely reported but virtually always fatal
• Occurs in immunosuppressed patients
• In normal patients where donor is HLA
homozygous and patient shares a haplotype
allowing proliferation and expansion of donor
lymphocytes
• Rare but occurrence commoner where fresh
blood, donations from relatives, or where
there is a restricted genetic pool i.e. Japan
• Prevented by irradiation of product
TA-GVHD
•
•
•
•
•
•
•
•
1-6 weeks post transfusion
Fever
Rash
Liver dysfunction
Diarrhoea
Pancytopenia
Skin/bone marrow biopsy
Presence circulating donor lymphocytes
Post-Transfusion Purpura
• Thrombocytopenia 5-12 days post
transfusion associated with anti HPA
antibodies in the patient
• Shot 11 cases
• All women previous pregnancies
• 4 previously transfused
• Platelet alloantibody: HPA-1a in 8/9 cases
• Rx IvIg
Bacterial Contamination
• Infective shock 1:2 million units
transfused
• 15 cases reported to SHOT since 1996
• 5 fatalities
• largest cause of infection related deaths
from blood transfusion
Prevention of Transmissible
Disease
• Careful selection of Donors
›
›
›
›
Exclude IVDU
Homosexuals/bisexuals
promiscuity
Other exposures e.g. visits to malaria areas
• Laboratory Screening
›
›
›
›
›
HIV 1 + 2 & HIV PCR
HCV & HCV PCR
HBsAg + Core Antibody
VDRL
HTLV 1+2
Sources of Risk
• Infectious, but seronegative window period
• Immunosilent infection
• Variants of known agents
• Laboratory error
• New agents for which no test available
• Unknown agents
‘Window period’
HIV
HBV
HCV
22 days
60 days
80 days
HIV Markers During Early Infection
HCV Markers During Early Infection
Residual Risk of Transfusion
Transmitted Disease
• HIV
1:3000 000
• HCV
1: 500 000
• HBV
1: 100 000
JOR after Shreiber et al NEJM 1996
Risk of Dying in any 1 year
•
•
•
•
•
RTA
Playing soccer
Homicide
Train Accident
Lightning
Risk Estimate
1: 8 000
1: 25 000
1: 100 000
1: 100 000-1:16
1: 1 000 000
Nucleic Acid Amplification
Testing NAT IBTS
• HCV NAT SNBTS Nov 99
• HIV NAT
Sept 01
• 467, 694 donations screened
• No HCV RNA, anti-HCV neg detected
• No HIV NAT
• UK 3: 3,500,000 HCV RNA pos
Viral Treatment of Blood
Components
• Solvent detergent FFP (pooled-6001500 donations) from voluntary
American donors has replaced single
unit FFP
• Use of psoralen (S59) Rx platelets
under investigation
Other Infectious Risks
• Viruses
– Parvo B19, CMV,EBV, HAV
– West Nile Virus
• Parasites
– Malaria.
– Trypanosomiasis
– Babesiosis
• Prions-vCJD
What is a Prion?
• Proteinaceous infectious particle
resistant to most procedures that modify
nucleic acids in blood
Human CJD
•
•
•
•
•
Type
Sporadic
Genetic
Iatrogenic
Variant
Cause
Idiopathic
Inherited, PrP mutation
medical accident
BSR via diet
Number of Cases of BSE Reported
in the United Kingdom
40000
35000
30000
25000
20000
15000
10000
5000
0
1987
1988
1989
1990
1991
1992
1993
1994
1995
1996
1997
1998
1999
2000
vCJD cases in the UK
Source: Department of Health (UK)
30
28
25
22*
20
18
15
15
10
5
10
10
1996
1997
UK
3
0
1995
1998
Year
1999
2000
2001
What next?
Inadvertent Population Exposure
Bovine BSE
Human vCJD
Human vCJD by iatrogenic spread
Can CJD be transmitted
through blood?
• Epidemiological
-
case-control studies
-
lookback
-
surveillance e.g. haemophiliacs
vCJD and blood transfusion
• Is there a risk?
– no documented evidence of
transfusion transmission in humans
– putative infective agent found in
lymphoid tissue
– BSE transmissible by blood from
sheep to sheep
CJD Blood Donor Exclusions
•
•
•
•
•
•
•
5 year Residence in UK 1980-1996
dementia
chronic neurological disorder
personal or family hx of CJD
recipients of human pituitary hormones
corneal transplant recipients
brain surgery pre 1992
vCJD and Blood Transfusion
• Current Precautions
– Donor exclusion criteria
– UK, Irish plasma not used for
fractionation
– 100% leucodepletion of all
components
FDA TSEAC 28-29 June, 2001
Indigenous risk assessment in European
countries
– UK 98% of total risk
– France 5% of UK risk
– Rest of Europe 1.5% of UK risk
Protective Measures
• Sourcing: country
• Sourcing: donor
• Processing
• Testing
• Appropriate use of blood/alternatives
West Nile Virus
• Flavivirus natural host birds,mammals
spread by mosquito
• 43 States in US
• 80% cases asymptomatic
• 20% mild illness
• 1% encephalitis
• 3989 cases -259 deaths
• 30 related to Transplant /Transfusion
Rh Haemolytic Disease
Mother RhD Neg
Father RhD Pos
DD, Dd
Baby
RBC
dd
Placenta
RhD+
Next Rh Pos
Babies
Neonatal jaundice
anemia, hydrops
intrauterine death
Mother
produces anti-D
antibodies
Prevention & treatment of Rh
Haemolytic Disease
• Prevention: Anti-D Immunoglobulin
• Incidence reduced from 18% to 1%
• Treatment of Affected Child
• Exchange Transfusion
• Monitoring in utero
• Ultrasound Amniocentesis
• Cordocentesis
• Intrauterine Transfusion
Haemolytic Disease of the
Newborn