Current Issues in Transfusion Medicine

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Current Issues in Transfusion Medicine

• First Year Graduate Medical Program
• September 2004
• Dr Peta Dennington

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Current Issues in Transfusion Medicine

• Risks of transfusion
• Current issues facing the donor side
• vCJD Guidelines
• Haemoglobin levels in donors
• Products
• Indications for use
• Adverse Transfusion Reactions
• Proposed leucodepletion
• Pathogen inactivation

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ARCBS PRODUCTS

• Whole Blood
• Red Blood Cells
• Standard, Buffy Coat Poor
• Platelets
• Platelet-Rich-Plasma, Buffy Coat Poor , Apheresis
• Plasma
• FFP, Cryoprecipitate, Cryosupernatant
• Plasma Products
• Procoagulants, Intragam P (IVIg),
  Immunoglobulins, Albumex

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BLOOD DONATIONS

• AUSTRALIA
• More than 1,000,000 per year
• NSW 305,000 per year
• 24 Collection Centres
• Sydney Metropolitan Area 50
• Regional Centres 50
• 2 Processing sites
• 1 Testing site

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DONOR SCREENING

• This has 3 parts
• Donor Questionnaire Form
• Identifies Risk Behaviour
• Wording is covered by legislation
• Legal Document - 5000 fine or 1 year gaol
• Donor Interview
• Confidential one-on-one
• Auditory and visual privacy
• National Donor Selection Guidelines
• Donor testing

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All Donations are tested every time for

• HBsAg
• HCV Ab and NAT
• HIV Ab and NAT
• HTLV-1Ab
• Syphilis
• ABO and Rh (D) Type
• RBC Antibody Screen
• CMV Ab (selected only)

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INFECTIOUS RISKS OF TRANSFUSION IN AUSTRALIA

• HIV Ab NAT
• Considerably less than 1 in 1 Million
• HCV Ab NAT
• Approximately 1 in 900,000
• HBV
• Approximately 1 in 500,000
• MALARIA
• 5100,000,000
• Bacterial Contamination
• 1 80 000 (UK Data)

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MANAGEMENT OF vCJD

• Donor Deferral Policy Version 1 introduced on
  December 21 2000
• Precautionary measure by Commonwealth Department
  of Health
• All donors who have spent a cumulative total of 6
  months or more in UK, EIRE
• Donor deferral in Australia for this reason would
  affect 2-5 of donors - affected 6
• Accompanied by active recruitment strategy for
  replacement donors
• Australia undertook donor travel survey to assess
  impact - Travel Simulator - used to form further
  policy

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MANAGEMENT OF vCJD

• Donor Deferral Policy Version 2 introduced July 1
  2003
• Donors who have had a transfusion in the UK and
  EIRE
• Little impact as these people deferred with
  Version 1
• First possible case in Lancet December 2000
• Second case to be published soon.
• First test announced - impact unknown

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Donor Haemoglobin Guidelines

• ARCBS now regulated under the TGA for fresh
  products
• Council of Europe Guidelines are now mandated
• Many differences but major one is donor Hb level
  prior to donation
• Increase in eligibility levels without donor
  management and recruitment strategies would have
  major effect on blood supply

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Donor Haemoglobin Guidelines

• To be introduced in two stages
• On January 1 2004, minimum level to changed to
• Males 125g/L to 128g/L
• Females 115g/L to 118g/L
• Next increment after review
• Males 128g/L to 130g/L
• Females 118g/L to 120g/L
• Further initiatives in donor recruitment to
  maintain blood supply

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Types of Platelet Products

• PRP Platelets - historical
• BCP Platelets
• Apheresis Platelets
• leuco-reduced
• non-matched
• Antigen-matched eg HLA
• Crossmatch compatible
• Please perform HLA Type at diagnosis patients who
  may become refractory
• Paediatric apheresis platelets are coming

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Opti-System BC vs PRP Method
Conventional Soft Spin
Opti-Systemä Hard Spin
Platelets
Platelets Leukocytes
í
Leukocytes
First Centrifugation
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Pooled Buffy Coat Method
T-Sol
BC
BC
BC
BC
Sterile Connect
Pooling Transfer Pack
Pool
Soft Spin
PL2410
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Opti-Systemä BC vs Conventional PRP Method
Opti-Systemä Soft Spin
Conventional Hard Spin
Pooled PC
Single PC
Pooled BC
PPP
Platelets in Supernatant
Platelets in a Pellet
Second Centrifugation
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Buffy Coat Platelets
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Apheresis Platelets
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INDICATIONSFOR PLATELET TRANSFUSION

• BLEEDING DUE TO
• THROMBOCYTOPAENIA
• FUNCTIONALLY ABNORMAL PLATELETS
• Thrombocytopenia does not equal Platelet
  Transfusion

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1. THROMBOCYTOPENIA

• Marrow suppressive chemotherapy
• Consumptive coagulopathy
• Rarely in situations of rapid platelet
  destruction
• ITP ( Immune Thrombocytopenia)
• TTP (Thrombotic Thrombocytopenic Purpura)
• Contraindicated in Heparin induced
  thrombocytopenia

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2. FUNCTIONALLY ABNORMAL PLATELETS

• Haematological disorders
• Myeloproliferative Disease
• Myelodysplastic Disease
• Aspirin and other anti-platelet drugs
• Acquired Platelet Dysfunction

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Clinical Practice Guidelines Platelets

• Likely to be appropriate
• lt10 with no risks or lt20 risk factors
• maintain gt 50 during surgery or procedures
• inherited/drug induced defects
• bleeding and thrombocytopenia
• 50 and massive transfusion
• higher counts in neurosurgical/ ophthalmological
  procedures

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BLOOD ANTIBODIESGROUP IN PLASMA

• O ANTI-A ANTI-B
• A ANTI-B
• B ANTI-A
• AB NIL

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CROSSING THE ABO BARRIER IN PLATELET TRANSFUSION

• 1. PLASMA INCOMPATIBILITY
• PLATELET PATIENT
• GROUP GROUP
• O A,B,AB
• A B,AB
• B A,AB
• Transfusion of incompatible anti A or anti B
• USUALLY NOT CLINICALLY SIGNIFICANT
• OCCASIONAL POSITIVE DAT

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2. PLATELET INCOMPATIBILITY

• PLATELET PATIENT
• GROUP GROUP
• A O,B
• B O,A
• AB O,A,B
• RECOVERY SLIGHTLY REDUCED
• BUT NOT CLINICALLY SIGNIFICANT.
• ABO COMPATIBLE PLATELETS PREFERRED
• In a life threatening situation, the best
  platelets are the nearest ones!

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PLATELET PRODUCT

• STORAGE TIME LIMITS
• At 20-24 degrees Celsius
• AGITATION 5 DAYS
• NO AGITATION ASAP
• Transfuse within 4 HOURS
• Platelets that are refrigerated, quickly become
  irreversibly damaged.

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RED BLOOD CELLS

• Red Cells from one unit of blood
• Volume of 340-400ml
• Haematocrit of 50-60
• Does not contain functional platelets or
  coagulation factors

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RED BLOOD CELLS

• Donor red cells and recipient plasma are
  ABO-compatible
• Contains a minimal amount of plasma (ABO
  alloantibodies) so can be used in situations of
  ABO non-identical compatibility e.g
• Group O RCC to Group A, B, AB
• Group A or B to Group AB
• One unit should raise the haematocrit by 3 or
  the haemoglobin by 10g/L in an adult patient with
  an intact spleen

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INDICATIONS FOR RED CELL TRANSFUSION

• To improve oxygen carrying capacity
• Some volume replacement
• Component of choice for patients with a
  symptomatic deficit in oxygen carrying capacity

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MANAGEMENT OF ANAEMIA

• Determine the cause of the anaemia
• Determine if the anaemia needs to be treated
• Determine the appropriate treatment
• Haematinics - Iron, B12, Folate
• Red Cell Transfusion
• Erythropoietin
• Anaemia does not equal Red Cell Transfusion

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Recommendations
Intro 1. Transfusions of blood products should
only be given when the expected benefits to the
patient are likely to outweigh the potential
risks 2.The decision to transfuse red blood cells
should be based on clinical judgement of patient
factors, response to any previous transfusion,
and haemoglobin levels
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Recommendations

• THE GUIDELINES
• 3. Red blood cell transfusion is likely to be
  inappropriate when Hbgt100g/L unless there are
  specific indications (level I evidence)
• If red blood cells are given at this haemoglobin
  level, reasons for the transfusion should be well
  documented

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Recommendations

• THE GUIDELINES
• 4. Red blood cells may be appropriate when Hb is
  in the range 70100g/L (level IV evidence)
• In such cases, the decision to transfuse should
  be supported by the need to relieve clinical
  signs and symptoms and prevent significant
  morbidity and mortality

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Recommendations

• THE GUIDELINES
• 5. Use of red blood cells is likely to be
  appropriate when Hblt70g/L (level I evidence)
• In patients who are asymptomatic and/or where
  specific therapy is available, lower threshold
  levels may be acceptable

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Recommendations

• IMPLEMENTATION and MAINTENANCE
• 6. Documentation used in ordering or
  administering red blood cells should summarise
  the clinical recommendations of these guidelines
  and collect standardised data items
• Clinical and laboratory indications for red
  blood cells should be accurately recorded in that
  documentation and in the patients medical record

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Recommendations

• IMPLEMENTATION and MAINTENANCE
• 7. In all situations where red blood cell therapy
  is given, a process for clinical review should be
  in place to monitor the appropriateness and
  safety of its use and to develop systems for the
  implementation of these guidelines

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Recommendations

• IMPLEMENTATION and MAINTENANCE
• 8. As part of the informed consent process, a
  patient should be given clear explanation of the
  potential risks and benefits of red cell therapy
  in his or her particular case

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RED BLOOD CELLS

• Storage Time Limits
• Refrigeration
• 4-6 Deg C 42 days CPD
• Non-refrigerated Max. 30mins
• Room temperature
• NOTE (unit will not be reissued)
• Transfuse within 4 Hours

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INDICATIONS FOR FRESH FROZEN PLASMA

• CONTROL OF BLEEDING DUE TO DEFICIENCY OF
  COAGULATION FACTORS
• LIVER DISEASE
• WARFARIN OVERDOSE
• MASSIVE TRANSFUSION

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NOT INDICATED FOR

• VOLUME REPLACEMENT
• SPECIFIC FACTOR DEFICIENCIES FOR WHICH
  CONCENTRATES ARE AVAILABLE

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FRESH FROZEN PLASMA

• Storage Time Limits
• Frozen
• lower than -18 Deg C (AABB) 1 Year
• lower than - 30 Deg C (TGA)
• Thawing Instructions ASAP
• 30-37 Deg C
• Transfuse ASAP

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INDICATIONS FOR CRYOPRECIPITATE

• FIBRINOGEN REPLACEMENT
• CONGENITAL HYPOFIBRINOGENAEMIA
• ACQUIRED HYPOFIBRINOGENAEMIA
• DIC
• No longer used for FACTOR VIII VON WILLEBRAND
  FACTOR REPLACEMENT

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CRYOPRECIPITATE

• Storage Time Limits
• Frozen 1 Year
• lower than -18 Deg C (AABB)
• lower than -30 Deg C (TGA)
• Thawing Instructions
• 30-37 Deg C ASAP

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SIDE EFFECTS OF FRESH BLOOD COMPONENTS

• Side effects can be categorised
• result of receiving Allogeneic graft
• result of storage
• result of adverse event e.g. incorrect blood
  product given
• result of massive transfusion

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SIDE EFFECTS OF FRESH BLOOD COMPONENTSEffect of
allogeneic graft

• IMMEDIATE AND DELAYED TRANSFUSION REACTIONS DUE
  TO RED CELL AgAb REACTIONS (Haemolytic and
  non-haemolytic)
• TRANSMISSION OF INFECTIOUS DISEASE
• ALLOIMMUNIZATION OF THE RECIPIENT
• GRAFT-VS-HOST DISEASE (GVHD)
• FEBRILE REACTIONS (FNHTR)
• ALLERGIC REACTIONS

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SIDE EFFECTS OF FRESH BLOOD COMPONENTS

• Effect of product storage
• BACTERIAL CONTAMINATION OF BLOOD
• Result of adverse event
• HAEMOLYTIC TRANSFUSION REACTIONS - ABO
  Incompatibility

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SIDE EFFECTS OF FRESH BLOOD COMPONENTSMassive
transfusion

• CIRCULATORY OVERLOAD REACTIONS
• IRON OVERLOAD
• METABOLIC COMPLICATIONS OF (a) HYPOTHERMIA (b) C
  ITRATE TOXICITY (C) ACIDOSIS (d) ALTERATIONS IN
  POTASSIUM - HYPOKALEMIA OR HYPERKALEMIA

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Bacterial Contamination(Data from UK SHOT Scheme)

• Predominant cause of post transfusion infection
• 25 products - 21 platelets, 4 RBCs
• Majority were skin contaminants
• Risk of infection - 1 in 80 000
• Risk of death - 1 in 340 000

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Strategies to reduce bacterial contamination

• ARCBS - routine sterility testing
• Strategies under evaluation
• review of donor arm sterilisation
• diversion of first 30 mL of blood
• New technologies
• bacterial testing of platelets

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Incorrect Blood Component Transfused

• 61 of adverse reactions reported through SHOT
• ABO Incompatibility - 161
• Rh Incompatibility - 73
• ABO/Rh Compatible ICBT- 195
• Rh (D) administered erroneously - 37
• Risk for autologous products as well as
  homologous transfusion

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SHOT Case Study 1 (SLIDE 1)

• Two patients on the same ward shared the same
  surname
• Patient 1 (group O) did not need a transfusion
  blood was brought for patient 2 (group A),
  checked, and given to patient 1.

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SHOT Case Study 1 (SLIDE 2)

• Patient complained of generalised pain a
  transfusion reaction was queried but was not
  acted upon
• Patient died within 6 hours
• Hospital review led to change of wording on
  compatibility labels

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SHOT Case Study 2

• Two nurses were interrupted while checking blood
  in the treatment room (local policy)
• A further unit was delivered, picked up in error
  and transfused
• Error rapidly discovered -no ill effects
• Avoid transfusions at night

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SHOT Out- patient problems

• No wrist bands
• Knowing who the patient is
• Anticipating who will be in the bed
• Two patients being transfused in an outpatient
  setting shared one drip stand.

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SHOT Recommendations Prescribing and sampling

• Prescribers must know what their patients need
• Staff taking samples for transfusion testing must
  at all times follow strict procedures to avoid
  confusion between patients.
• Sample tubes must never be pre-labelled and
  labelling must be completed for one patient
  before moving on to the next.
• Special care is required when dealing with
  unknown multiple casualties

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SHOT Recommendations BLOOD BANK

• Keep reviewing procedures/systems/training
• Check historical record always
• Put special requirements on computer
• Set minimum identification requirements for
  collection of blood from blood bank
• Make sure staff collecting blood are trained and
  know they are important

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Appropriate transfusion practice

• Consider benefit vs risk
• Use product appropriately
• Follow procedures for specimen collection,
  labelling and checking
• Observe aseptic techniques
• Document indication for transfusion in medical
  record
• Report any adverse reactions

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CROSSMATCHING

• 1. ABO and Rh(D) blood group
• 2. Antibody screen against a panel of common red
  cell antigens
• 3. Cross-match
• Full cross-match
• Immediate spin
• Clerical cross-match

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CROSSMATCHING

• Full cross-match
• - only if antibody is identified
• - takes at least 30 minutes
• Immediate spin
• - takes 5 mins
• - used to convert GS to cross-match
• - allows better use of inventory
• Group-specific blood

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MANAGEMENT OF MASSIVE TRANSFUSION

• 1. CPR and maintenance of blood pressure
• 2. Give O Rh(D) negative blood
• Take sample of blood group
• Notify laboratory that there is an emergency
• 3. Once blood group is known, give group specific
  blood

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MANAGEMENT OF MASSIVE TRANSFUSION

• 4. If more than 10 units required, consider
  changing
• - Rh (D) negative to Rh (D) positive
• - AB to A or B
• - B or A to O
• - Change back after bleeding has ceased
• 5. Give ABO compatible platelets if available, if
  not, give any available platelets

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ARCBS Plasma-derived Products

• Coagulation Factors
• Factor VIII - AHF Factor IX - MonoFIX-VF
• Prothrombinex (II,IX,X) Thrombotrol (AT111)
• Immunoglobulins
• Intragam P
• Normal Immunoglobulin
• Hyperimmune Globulins
• Zoster Tetanus
• Hepatitis B CMV
• Rh(D)
• Volume Expanders
• Normal Serum Albumin- Albumex

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LEUCODEPLETION

• Planning for leucodepletion
• Leucodepletion Reference Group
• 100 Platelets
• 30 RBCs depending on indication
• Being managed by the Commonwealth Department of
  Health
• Next step is Business Case

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Methods of Pre-storage Leucodepletion

• Filtration
• Whole Blood Filter - RBC.Plasma
• Red Cell Filtration of BCP RBC
• Platelet Filtration of BCP Platelets
• Apheresis Platelets

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Pathogen inactivation

• Treatment of fresh products to remove pathogens
• Need to preserve efficacy of product and safety
  to patients
• Photochemical methods being developed for RBCs
  and platelets
• Require leucodepleted product as starting point
• Will be expensive in terms of money as well as
  product loss

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Websites

• www.arcbs.redcross.org.au
• Circular of Information
• Transfusion Medicine Handbook
• www.nhmrc.org.au
• www.anzsbt.org.au
• www.csl.com.au
• www.aabb.com
• www.novoseven.com (Rec FVIIa)
• www.baxter.com (Rec FVIII)

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THE END