Blood Transfusion Dr Emer Lawlor, IBTS 3rd February 2003

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Blood Transfusion Dr Emer Lawlor, IBTS3rd
February 2003
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First Blood Transfusions
Harvey Discovered Circulation of Blood
1628
Wilkins Lower Transfusions from dog to dog
1665-66
1667
Jean-Baptiste Denis Performed first recorded
blood transfusions from animals to humans
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19th Century Transfusions
1818
James Blundell, Obstetrician
First transfusion of human to human
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Early transfusion Paris, France
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20th Century Transfusions
1901
Karl Landsteiner Discovers A, B, O Blood Groups
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20th Century Transfusions
1902
AB Group discovered
Importance of crossmatching blood between donor
recipient
1907
Sodium Citrate proposed as anticoagulant
1914
1936
First Blood Bank Barcelona, Spanish Civil War
Levine Landsteiner, Rhesus blood Group System
1940
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Bad Blood

• France, Switzerland, Italy, Netherlands,
• Germany, Denmark, Ireland,
• Australia, New Zealand,
• Canada, USA
• Japan

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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

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Blood Supply Chain

• Blood Donor Screening Criteria
• Donation Process
• Donation Testing
• Component preparation
• Plasma Products

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Donor Screening

• Self deferral of At Risk groups
• Health Questionnaire
• Microbiological screening of each donation

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Blood Donor Criteria

• Age 17-65 ( new donors until 60)
• Weight gt 50kg ( 7st 12Ibs)
• General health
• Specific illnesses
• Contact with infection

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Blood Donor Criteria

• HIV,Hepatitis risk
• Medication
• CJD
• Hb gt 13 M gt12 F

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Haemoglobin Testing
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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

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Alternatives to Voluntary Donors Directed

• Relatives or friends
• Not demonstrably safer
• Not voluntary
• Viral marker rates higher as often first time
  donors
• TA-GVHD

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Blood Donation

• 475mls Blood 63mls anticoagulant
• Red Cells
• Plasma
• Buffy Coat Platelets
• Red Cells Optimal Additive Solution
• Saline
• Adenine SAGM
• Glucose
• Mannitol
• Expiry date 35 days

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Blood Components and Products
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Blood Component Production
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Blood Component Production
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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

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Leucodepletion
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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

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Blood Donation Testing

• Microbiology markers
• Blood grouping and screening for high titre
  antibodies
• Quality monitoring

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A
O
B
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ABO Groups
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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

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ABO Grouping
Patient Red Cells
Test Reagents
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Cells v Serum
Serum v Cells
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Microbiology testing

• Current
• anti HIV 12
• HIV PCR
• HBsag
• HBc assay
• anti HCV
• HCV PCR
• anti HTLV1/2
• syphilis
• anti CMV

• Future
• Bacterial culture of components
• Prions

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Hospital Blood Transfusion Laboratory

• Patient/donor testing and product selection and
  issue

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Tests prior to transfusion
Hospital
IBTS

• ABO Rh typing
• Antibody screen

Patient
Donor
Donor

• ABO Rh typing
• Antibody screen

Compatibility Test (x-match) Donor red cells
patients serum Saline and LISS Coombs
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Antigens on Red Cells
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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

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Conventional Testing.
Weak reactions often difficult to interpret. Can
also be downgraded due to shaking the completed
test.
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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

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ABO/Rh Typing
Group B RhD positive
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Antibody Screening
Positive antibody screen. Antibody could cause a
transfusion reaction or affect an unborn baby.
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Purpose of Crossmatch

• Detect unsuspected ABO incompatibility
• Donor centre
• Error in laboratory
• Detection of unsuspected antibodies in lt1 cases

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Crossmatching
Crossmatch
ABO Group
Donor and patient compatible. Unit safe to
transfuse.
Patient B Positive
Recipient Serum Donor Red Cells
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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

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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

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Haemovigilance Looping the Loop

• Safety of the Transfusion Chain
• from Vein to Vein

Right Blood
Right Patient
Right Time



?
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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)

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Transfusion Chain

• Haemovigilance
• Adverse Reaction
• reporting
• Guidelines, Audit
• review

• Hospital
• patient sample
• Identification

• Transfusion
• Centre
• Blood Supplied

• Laboratory
• Ordering
• Testing
• Storage

• Patient
• Blood Administered
• Monitored

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NHO Incidents (category) 1999-2001
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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

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IBCT (n31) Site of First Error
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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 Elsewheres 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!

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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
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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
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Immediate Haemolytic Transfusion Reactions
IgM Anti A
A antigen
Complement Activated C1-9
Intravascular Haemolysis
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Causes of error in deaths due to haemolytic
reactions

• Blood given to wrong person
• Breach of identification procedures
• sample taken from wrong person
• given to person with same surname
• given to roommate
• Blood Bank errors
• Identification errors
• Wrong blood issued
• Serological errors

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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

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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
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Estimates of the risk of post-transfusion
complications (US Figures)
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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

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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

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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 17,000
• red cells 133,000

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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

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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

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Frequency of Transfusion Adverse Events

• Transfusion Associated
• Circulatory Overload 1200
• TRALI 15,000
• ABO incompatible transfusion 130,000-60,000
• Severe Anaphylactoid reaction 120,000
• GVHD/Post Transfusion Purpura 1750,000 to
  11mill
• Bacterial infection Red Cells Platelets 17,000
• Viral infection in Ireland - HIV 13.3 million
  
• - HCV 11 million
• - HBV
  1500,000

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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

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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

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CXR - 21/11/01
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CXR - 24/11/01
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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

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TA-GVHD

• 1-6 weeks post transfusion
• Fever
• Rash
• Liver dysfunction
• Diarrhoea
• Pancytopenia
• Skin/bone marrow biopsy
• Presence circulating donor lymphocytes

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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

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Bacterial Contamination

• Infective shock 12 million units transfused
• 15 cases reported to SHOT since 1996
• 5 fatalities
• largest cause of infection related deaths from
  blood transfusion

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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 12

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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

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Window period

• HIV 22 days
• HBV 60 days
• HCV 80 days

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HIV Markers During Early Infection
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HCV Markers During Early Infection
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Residual Risk of Transfusion Transmitted Disease

• HIV 13000 000
• HCV 1 500 000
• HBV 1 100 000

JOR after Shreiber et al NEJM 1996
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Risk of Dying in any 1 year

• Risk Estimate
• RTA 1 8 000
• Playing soccer 1 25 000
• Homicide 1 100 000
• Train Accident 1 100 000-116
• Lightning 1 1 000 000

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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

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Viral Treatment of Blood Components

• Solvent detergent FFP (pooled-600-1500 donations)
  from voluntary American donors has replaced
  single unit FFP
• Use of psoralen (S59) Rx platelets under
  investigation

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Other Infectious Risks

• Viruses
• Parvo B19, CMV,EBV, HAV
• West Nile Virus
• Parasites
• Malaria.
• Trypanosomiasis
• Babesiosis
• Prions-vCJD

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What is a Prion?

• Proteinaceous infectious particle resistant to
  most procedures that modify nucleic acids in blood

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Human CJD

• Type Cause
• Sporadic Idiopathic
• Genetic Inherited, PrP mutation
• Iatrogenic medical accident
• Variant BSR via diet

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Number of Cases of BSE Reported in the United
Kingdom
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vCJD cases in the UKSource Department of Health
(UK)
To 31st August, 2001
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What next? Inadvertent Population Exposure

• Bovine BSE
• Human vCJD
• Human vCJD by iatrogenic spread

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Can CJD be transmitted through blood?

• Epidemiological
• - case-control studies
• - lookback
• - surveillance e.g. haemophiliacs

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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

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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

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vCJD and Blood Transfusion

• Current Precautions
• Donor exclusion criteria
• UK, Irish plasma not used for fractionation
• 100 leucodepletion of all components

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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

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Protective Measures

• Sourcing country
• Sourcing donor
• Processing
• Testing
• Appropriate use of blood/alternatives

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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

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Rh Haemolytic Disease
Father RhD Pos DD, Dd
Mother RhD Neg dd
Placenta
RBC RhD
Mother produces anti-D antibodies
Baby
Next Rh Pos Babies
Neonatal jaundice anemia, hydrops intrauterine
death
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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

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Haemolytic Disease of the Newborn