By the end of this talk you should be able to:

Transcription

1 Blood Components

2 Learning Objectives By the end of this talk you should be able to: List the components made from whole blood Describe how blood products are produced and stored Understand the Indications for the Use and Selection Criteria for Red cell concentrates Platelets Fresh frozen plasma ( FFP) / Cryoprecipitate Understand when specific requirements may be required

3 Blood and Blood Products are derived from human donors and are capable of transmitting many infectious agents. However there is an expectation of zero risk

4 Definitions Blood Product any therapeutic substance prepared from human blood Blood Components prepared by NHSBT Platelets Red Blood Cells Fresh Frozen Plasma Cryoprecipitate White Blood Cells / Granulocytes Plasma Derivative Plasma proteins prepared from pools of human plasma under pharmaceutical manufacturing conditions (donations sourced from countries with a low risk of vcjd Coagulation factors Immunoglobulin Albumin

5 Quality Assurance Rely on consensus among experts as expressed in professional guidelines and standards Red Book - Guidelines for the Blood Transfusion Services in the UK BSH British Standards in Haematology MSBT - Microbiological Safety Blood & Tissues for Transplantation SaBTO - Advisory Committee on Safety of Blood, Tissues & Organs EU Directives 2002/98/EC and subsequent documents 2004/33/EC, 2005/61/EC and 2009/135/EC UKAS United Kingdom Accreditation Service EC Guide to GMP Good Manufacturing Practice All centres inspected by MHRA and hold Blood Establishment status under Blood Safety and Quality Regs, 2005

6 GMP - Quality Management Our aims are to: produce products that conform to specification carry out collection procedures that follow up to date guidelines manufacture products free from bacterial contamination and commonly occurring blood borne viruses correctly process, test, package and label products Regular monitoring is undertaken to ensure that blood components continue to meet their specifications 75% compliance except leucodepletion

7 Leucodepletion Since Nov all cellular components are filtered to a residual leucocyte count of: <5x10 6 per unit (95% confidence) in over 99% of units <1x10 6 per unit in over 90% of units Why? Reduce risk of vcjd Other Benefits reduced rates of NHFTRs HLA alloimmunisation CMV (and other cell-associated virus) transmission

8 Serological and Microbiological Testing Blood group serology tests Antibodies Microbiology Testing Nucleic Acid Testing All Donations ABO Rh and K grouping Antibody screen Some high Titre Anti A & B HIV 1+2 HBV HCV Syphilis HTLV 1+2 HCV HIV HBV Hep E Plus bacterial screening on all platelets Selected Donations Additional antigen phenotyping Paediatric antibody screening CMV T-Cruzi West Nile Virus Precautions to reduce the transfusion transmission of prion infected diseases Other discretionary microbiology tests may include: HbS (Sickle Cell Marker) Malaria parasite

9 Donor Selection UK blood donors are all volunteers Aged 17+ years and weight limit 50 Kg Can donate every... CD platelet donors every... Pre-donation health information and questioning regarding lifestyle Low risk of viral transmissions Ensures safe for donor to give Donor Selection Guidelines - identifies potential patient and donor related problems Excluded if received a transfusion after 1st Jan 1980 Hb level screened CuSO 4 test (125g/L females / 135g/L males)

10 Whole Blood Donation Red Book Guidelines Whole blood donation volume 450ml +/- 45ml Bled 66.5ml anticoagulant Citrate Phosphate Dextrose (CPD) for RBCs stored in Saline Adenine Glucose Mannitol (SAG-M) or Citrate Phosphate Dextrose Adenine (CPD-A1) for autologous Few patients require whole blood Small amount still produced for specific indications mostly paediatrics

11 Collection Packs Whole blood filter packs Allows leucodepletion before separation of the components Pack not suitable for platelet production Usually SAG-M Bottom and Top (BAT) pack Separation of component carried out before filtration Can be used to produce the same components as the WBF packs with the addition of platelets

12 Component Donation (Apheresis) Products directly leucodepleted Collects 2-3 adult doses of platelets Can be used to collect double dose red cells

13 Component Production Benefits of separating into components Allows provision of a concentrated form of a clinically effective product NBS Enables treatment of a specific deficiency without wasting other components Allows for storage at optimal conditions NBS

14 Product Labelling In process labelling - all critical stages of processing are under computer control NBS

15 Activity Labelled blood pack (as prescribed by BSQR 2005) What do all the numbers and barcodes mean See Booklet

16 Final Label

17 Why are Specific Requirements important? Prevention of transfusion associated Graft versus host disease IRRADIATION Prevention of CMV infection or reactivation CMV NEGATIVE Prevention of red cell antibody production PHENOTYPE MATCHED Increase platelet increments post transfusion HLA/HPA SELECTED Prevent anaphylactic reactions WASHED

18 Red Cell Products Red Cells in (105ml) Optimal Additive Solution (SAG-M) RBCs re-suspended in SAG-M Plasma Reduced Red Cells ~220ml plasma removed Saline Washed Red Cells Plasma removal - residual protein <0.5g/unit Also available Frozen CMV negative Phenotyped Irradiated Neonatal

19 Mar-99 Apr-01 Jul-01 Oct-01 Jan-02 Apr-02 Jul-02 Oct-02 Jan-03 Apr-03 Jul-03 Oct-03 Jan-04 Apr-04 Jul-04 Oct-04 Jan-05 Apr-05 Jul-05 Oct-05 Jan-06 Apr-06 Jul-06 Oct-06 Jan-07 Apr-07 Jul-07 Oct-07 Jan-08 Apr-08 Jul-08 Oct-08 Jan-09 Apr-09 Jul-09 Oct-09 Jan-10 Apr-10 Jul-10 Oct-10 Jan-11 Apr-11 Jul-11 Oct-11 Jan-12 Apr-12 Jul-12 Oct-12 Jan-13 Apr-13 Jul-13 Oct-13 Jan-14 Apr-14 Jul-14 Oct-14 Jan-15 Apr-15 Jul-15 Oct-15 Jan-16 Apr-16 Jul-16 Oct-16 Jan-17 Apr-17 Total O Neg Red Cell Usage March 1999 April 2017 Moving Annual Total of Red Cell [Full Unit Equiv] Issues to Hospitals - 000s MAT Total MAT O Neg

20 Red Cells in Additive Solution Routinely produced- available off the shelf Cost approx. 125 per unit Concentrated red cells Removal of nearly all of the plasma Re-suspended in SAG-M What are the advantages of using SAG-M Adenine helps to maintain red cell metabolism Mannitol decreases red cell lysis Flow rate approaching that expected of whole blood

21 Changes Due to Red Cell Storage Glycolysis / energy production slows during storage due to: Storage temperature glycolysis ~40x slower at 4 o C Fall in ph accumulation of lactic acid Energy related RBC changes during storage: Membrane Stability Gas Exchange Ion Transport (Increase in potassium levels on storage)

22 Red Cells Neonatal Use Neonatal units are specifically selected / screened CMV, HBS, PANT, Lysin neg May be divided into 6 equal volumes using the paedipak system or remain in an adult size pack (LVT) in SAG-M Blood for IUT or Exchange 5 days old plasma reduced In CPD anticoagulant Irradiated for IUT or following previous IUT

23 Frozen-Thawed Red Cells Glycerol: acts as an intracellular/ extracellular cryoprotectant Storage up to 10 years -60 o C to -80 o C if stored in a freezer -140 o C to -150 o C if stored in liquid N 2 Glycerol removed after thawing Sorbitol and saline washes If open system use within 24 hrs (4 o C ± 2 o C) If closed system used 72hrs (4 o C ± 2 o C) RBC damage during the process Hb: >36g/unit supernatant Hb <2g/unit

24 Red Cell Storage Requirements Red Cell Recovery >70% of RBCs viable 24 hours post-transfusion Red Cell Survival maintenance of a normal RBC life-span Red Cell Function maintaining normal oxygen transport Hb content Lower specified limit 40g/unit Must be store in a fridge which - complies with BS4376 Capable of maintaining products at a core storage temperature of 4 o C ± 2 o C Air temperature maintained and monitored

25 Red Cell Products - Summary Red Cell Product Whole Blood (Autologous) Red cells (plasma reduced) SAG-M red cells Constituents/Quality Parameters 470ml ± 50ml in CPD-A1 Hb >40g/unit 280ml ± 60ml in CPD Hb >40g/unit RBC s + 105ml SAG-M 280ml ± 60ml : Hb >40g/unit Shelf Life 35 days 28 days 35 days Saline washed red cells (if resuspended in SAGM) Thawed washed red cells Hb > 40g/unit Residual protein <0.5g/unit Frozen, thawed and washed RBC s. Hb >36g/unit Closed system prep 14 days Closed system prep 72hrs

26 Indications For Transfusion of Red Blood Cell Components Reason for transfusion To raise the oxygen carrying capacity of the blood by increasing the haemoglobin concentration in the patient when it has been reduced by red cell loss or reduced erythropoesis and where alternative treatments are ineffective or inappropriate

27 Red Cell Concentrates Commonly used for Correction of anaemia Oncology and renal patients Audits in the UK show the inappropriate use of blood components is 20% or more What parameters can be used to indicate the need for a red cell transfusion? Studies show that medical patients cope well with haemoglobin concentrations of 70g/L (even down to 50g/L) No reliable parameters to guide the need for red cell transfusion No universal trigger

28 Clinical findings - Conclusions Decision to transfuse is a complex clinical one dependant on Cause of anaemia Patients ability to compensate for anaemia? Further blood loss Patient s clinical condition Figures change depending on new evidence In the absence of bleeding - use the minimum number of RBCs to achieve a target Hb Consider the size of the patient

29 Clinical findings Consider symptoms such as: Shortness of breath and fatigue subjective but useful in determining need in patients with chronic anaemia Changes in respiratory rate and pulse difficult to interpret Deterioration of mental function too subtle to be of clinical use Acute anaemia often dependant on volume of blood lost Chronic anaemia symptoms depend on age, level of activity, coexisting medical problems e.g. cardiovascular / respiratory disease Haemoglobin concentration transfusion to increase oxygen carrying capacity but also to avoid tissue hypoxia

30 Peri-operative Transfusion (elective surgery) Manage patient so that transfusion is not needed Pre-op checks for anaemia Stop anti-platelet drugs pre-op Reverse anticoagulation pre-op Consider lower transfusion threshold Use of pharmacological agents to reduce surgical bleeding Use of cell salvage where appropriate

31 Indications for Transfusion of RBC (BSH guidelines 2001 and NBTC Indication Codes 2016) Acute Bleeding frequently measure Hb to guide use of RBCs Hb <70g/L stable patients Hb 80g/L if cardiovascular disease (target of g/L) Chronic transfusion dependent patients Transfuse to maintain Hb which prevents symptoms - 80g/L initially and adjust as required Haemoglobinopathy patients require individualised thresholds Post radiotherapy - Transfuse to maintain Hb 110g/L Chronic anaemia - Cause should be established and red cell transfusions should not be given where effective alternatives exist

32 Indications - Irradiated Red Cell Products Patients receiving transfusions from 1st or 2nd degree relatives Patients receiving granulocyte transfusions Patients receiving HLA matched platelets All intrauterine transfusions (IUT) Some neonatal red cell transfusions - if there has been a previous IUT All exchange transfusions (providing it does not cause a delay) Patients with Hodgkin lymphoma Patients receiving allogeneic stem cell (HSC) grafts Until GvHD prophylaxis is complete or lymphocytes > 1x10 9 /L Patients with severe T lymphocyte Immunodeficiency Patients on purine analogue drugs or anti-thymocyteglobulin

33 Indications - CMV Negative Red Cell Products SaBTO recommendations CMV Neg RBCs for Intra-uterine Transfusions and Neonates - up to 28 days post EDD Pregnant Patients - for elective transfusions during pregnancy (not during delivery) Do not delay emergency transfusion if CMV negative components not available The following should receive leucodepleted blood products... But CMV PCR monitoring should be considered HIV and immunodeficient patients Haemopoetic stem cell transplant patients - adults and children Organ transplant patients

34 Selection of Red Cell Products for Fetus/Neonate/Infant Intrauterine Transfusion - Component specification (BSH 2004/2005 and revision 2016) Group O (HT negative) Usually D negative (rr) IAT cross match compatible with mum s plasma antigen neg for the relevant antibodies + K negative < 5 days old In CPD not SAG-M preservative Irradiated, CMV negative, HbS negative, Hep E neg Haematocrit between 0.70 and 0.85 (Council of Europe guidelines) Donors must have given at least one micro-neg donation in last 2 years Negative for clinically significant alloantibodies by IAT (PANTS Neg)

35 Exchange Transfusion Component specifications (BCSH guidelines 2004/2005 and revision 2016) Group O or ABO compatible with maternal and neonatal plasma D negative or identical to neonate Antigen negative to any red cell antigens to which mum has antibodies IAT compatible with mum s plasma < 5 days old to ensure optimal red cell function and low K+ levels Irradiated and transfused within 24hrs (if does not cause a delay) CPD anticoagulant CMV negative, Hep E neg Haematocrit of

36 Small Volume Transfusions Component specifications: BSH guidelines 2004/2005 and revision 2016 ABO compatible with mum and infant D compatible (or Rh D negative) IAT compatible with mum s plasma < 35 days old (SAG-M) (Irradiated CMV and Hep E negative) Usually infused in small volumes (paediatric splits) from a single donor

37 Case Studies

38 Where are they made? Bone Marrow What is their function? Platelets Stop bleeding by forming a clot. Spread across damaged vessel by a process called adhesion. Grow sticky tentacles send out chemicals to attract more platelets - How long are they in the circulation? days - What is a normal platelet count? X10 9 L

39 Platelet Components Produced from 1 of 2 processes A pool of buffy coat derived platelets A platelet apheresis donation All leucocyte depleted D negative products produced Also available CMV negative, irradiated Suspended in platelet additive soln. (24 hour expiry) HLA and HPA selected platelets Specification 240 x 10 9 per unit in approx. 250mL plasma

40 Pooled Platelets - Buffy Coat Derived Bleed time: <15 mins Use of bottom-and-top type blood bags Buffy coat left after red cells and plasma extracted. 4 buffy coats pooled with platelet additive solution (PAS) using a sterile docking system Platelets are extracted following centrifugation Leucodepletion occurs at end of the process Initial separation normally within 12 hrs NBS

41 Platelets Apheresis LD Collected using dedicated intermittent flow (apheresis) cell separator machines More platelets collected per donor double and triple doses More plasma in final product NHSBT can provide HLA / HPA matched/compatible Small volume platelets (~60ml) for neonates/children (CMV neg) Hyperconcentrated for IUTs (50-100ml conc. 2-4 x10 12/ L)

42 Preventing Bacterial Transmission Better arm cleaning and diversion pouch (2004) Most bacteria are in the skin plug and first few ml of donation Diverted blood taken into sample tubes Bacterial Screening Automated culture (BactALERT) implemented 2011 Sampling at 36h and released to hospitals min. 6h later Shelf life increased to 7 days

43 Bacterial Transmission Excellent culture medium Bacteria mainly from the donor skin at collection One of top 3 causes of transfusionrelated death in the developed world 1 in 2000 packs positive at 5 days Fatal in 1:25 80,000 transfusions

44 Platelets Storage Stored in an approved incubator at 22 o C ± 2 o C 7 days expiry if bacterial screening Storage designed to improve gas exchange, avoid anaerobic metabolism and maintain ph ph at end of storage Mixing (agitator) plastic gas permeable packs Logistical problems: off-the-shelf product

45 Principles of Platelet Transfusion Platelets are used in 2 distinct situations Prophylactic to prevent bleeding Routine use in non bleeding patients In the presence of additional risk factors for bleeding e.g. sepsis, therapeutic use of antibiotics, or abnormalities of haemostasis Do not routinely transfuse more than 1 ATD Therapeutic to treat active bleeding

46 Use of Prophylactic Platelet Transfusions Do not routinely transfuse more than 1 ADT dose Reversible bone marrow failure if <10 x 10 9 /L Sepsis / haemostatic abnormality x 10 9 /L Prior to invasive procedure or surgery if Central venous line <20 x 10 9 /L Pre lumbar puncture / spinal anaesthesia <40 x 10 9 /L Pre liver biopsy / major surgery <50 x 10 9 /L Epidural anaesthesia <80 x 10 9 /L Pre critical site surgery e.g. CNS <100 x 10 9 /L In a 70Kg adult, one adult therapeutic dose (ATD) typically gives an immediate rise in platelet count of approx x10 9 /L

47 Indication codes cont. Therapeutic use to treat bleeding Major haemorrhage plt <50 x 10 9 /L Critical site bleeding (e.g. CNS / brain injury <100 x 10 9 /L Clinically significant bleeding <30 x 10 9 /L Specific clinical conditions DIC pre procedure or if bleeding Primary immune thrombocytopenia (emergency treatment pre procedure/severe bleeding) Platelet dysfunction Consider if critical bleeding and on anti-platelet medication Inherited platelet disorders

48 Contraindications to Platelet Transfusion Unless life-threatening haemorrhage Prior to bone marrow biopsy Chronic bone marrow failure Autoimmune thrombocytopenia Thrombotic thrombocytopenic purpura (TTP) Heparin induced thrombocytopenia (HIT) Acute arterial thrombosis can result

49 Annie, 79 Long standing myelodysplasia On 6 weekly red cell transfusions Typical FBC: Hb 82g/L, WBC 17.1, platelets 9 Not bleeding Should she have regular platelets?

50 Michael, 59 Long standing ITP, does not respond to standard treatment Platelet count ranges from 8-25 Suffers from troublesome epistaxis and feels he cannot live life to the full Planned laporoscopic splenectomy Pre-op platelets 11 Should he have platelets?

51 Donna, 24 AML post chemo Hb 82g/L, WBC 0.4, plt 12 Needs marrow aspirate to assess response Should she have platelets prior to the procedure?

52 Mar-01 Jun-01 Sep-01 Dec-01 Mar-02 Jun-02 Sep-02 Dec-02 Mar-03 Jun-03 Sep-03 Dec-03 Mar-04 Jun-04 Sep-04 Dec-04 Mar-05 Jun-05 Sep-05 Dec-05 Mar-06 Jun-06 Sep-06 Dec-06 Mar-07 Jun-07 Sep-07 Dec-07 Mar-08 Jun-08 Sep-08 Dec-08 Mar-09 Jun-09 Sep-09 Dec-09 Mar-10 Jun-10 Sep-10 Dec-10 Mar-11 Jun-11 Sep-11 Dec-11 Mar-12 Jun-12 Sep-12 Dec-12 Mar-13 Jun-13 Sep-13 Dec-13 Mar-14 Jun-14 Sep-14 Dec-14 Mar-15 Jun-15 Sep-15 Dec-15 Mar-16 Jun-16 Sep-16 Dec-16 Mar-17 Platelet Usage March 01 March 17 Moving Annual Total of Platelet Issues to Hospitals - 000s Total MAT A Neg MAT

53 Requirements for Selection of Platelets Patient s ABO Group First Choice Second Choice Third Choice O O A or B (high titre neg) A A B (high titre neg) B B A (high titre neg) AB AB B or A (high titre neg) O (high titre neg) O (high titre neg) O (high titre neg) Irradiated - Patients at risk of TA GvHD CMV negative - All IUT and neonatal platelet transfusions

54 Selection of Platelets ABO Matched The importance of ABO compatibility in relation to platelet transfusion is controversial ABO antigens are present on platelets but density is much less than on red cells Now suspended in PAS so low risk of donor anti-a and Anti-B D Matched D neg platelets should be given to D neg patients particularly females of child bearing age If D pos platelets are transfused to a D neg female it is recommended that anti-d is given

55 Selection of Platelets for the Fetus / Neonate / Infant Component specification: BSH guidelines 2004/2005 Intrauterine Group O D negative (HT negative) Small Volume ABO and D identical or compatible Platelet specific alloantigen (HPA) compatible with maternal platelet antibody HPA compatible in infants with alloimmune thrombocytopenia (AITP) Collected by component donation Collected by component donation Irradiated Irradiated (if previous IUT) CMV Neg, Hep E neg CMV neg, Hep E neg Concentration of at least 2000 x 10 9 /L No further concentration required (Platelet splits)

56 Risks Associated with Platelet Transfusions Reduced effectiveness of future platelet transfusions Alloimmunisation In the absence of alloimmunisation increment reduces as number of platelet transfusions increases Febrile non-haemolytic transfusion reactions Allergic reactions Transfusion Transmitted Infections (bacterial) Transfusion Related Acute Lung Injury

57 Plasma and Cryoprecipitate

58 Plasma Products Routinely produced and leucocyte depleted during preparation Do not transmit CMV or HTLV No reported bacterial infections Non-UK plasma used for children born after 1st Jan 1996 (vcjd risk)

59 Fresh Frozen Plasma (FFP) Donors must meet the following criteria Male donors Bleed time must not exceed 15 minutes Rapid production to conserve labile coagulation factors Contains coagulation factors, including labile (V and VIII) and vitamin K dependent factors II, VII, IX, X (all > 0.7 IU/ml

60 Fresh Frozen Plasma Contains Labile and stable components of the coagulation, fibrinolytic and complement systems Proteins that maintain osmotic pressure and immunity Fats, carbohydrates and minerals in concentrations similar to those in circulation Dose 15ml/Kg body weight (equivalent to 4 units for an adult)

61 Cryoprecipitate Preparation: cryoglobulin fraction produced by controlled thawing of FFP at 4 o C ± 2 o C Precipitate isolated and re-frozen (<2 hours) in ~35ml of autologous plasma By-product Cryo depleted plasma Precipitate contains Factor VIII, von Willibrand factor, Fibrinogen, Factor Xlll and Fibronectin

62 FFP / Cryoprecipitate storage Store below -25 o C Shelf-life: up to 3 years Products must not be allowed to thaw at any time during storage (must not be re-frozen) use within 4 hrs (if held at 20 o C to 24 o C) FFP only use within 24 hrs (if stored at 4 o C) Management of unexpected major haemorrhage approved extension of the post-thaw expiry of FFP from 24 hours to 120 hours (5 days) when stored between 2-6 C.

63 Plasma products summary COMPONENT CONSITUENTS / QUALITY PARAMETERS FRESH FROZEN PLASMA (FFP) CRYO- PRECIPITATE * pre-freeze value Nominal volume >150ml FVIIIc conc of >0.7iu/ml (leucocyte count <5x10 6 /unit and platelets <30x10 9 /l*) Cryoprecipitate from an FFP (nominally ~35ml); fibrinogen >140mg/unit; FVIIIc >70iu/unit SHELF -LIFE 3 years 3 years

64 FFP UK FFP Mar-01 Jun-01 Sep-01 Dec-01 Mar-02 Jun-02 Sep-02 Dec-02 Mar-03 Jun-03 Sep-03 Dec-03 Mar-04 Jun-04 Sep-04 Dec-04 Mar-05 Jun-05 Sep-05 Dec-05 Mar-06 Jun-06 Sep-06 Dec-06 Mar-07 Jun-07 Sep-07 Dec-07 Mar-08 Jun-08 Sep-08 Dec-08 Mar-09 Jun-09 Sep-09 Dec-09 Mar-10 Jun-10 Sep-10 Dec-10 Mar-11 Jun-11 Sep-11 Dec-11 Mar-12 Jun-12 Sep-12 Dec-12 Mar-13 Jun-13 Sep-13 Dec-13 Mar-14 Jun-14 Sep-14 Dec-14 Mar-15 Jun-15 Sep-15 Dec-15 Mar-16 Jun-16 Sep-16 Dec-16 Mar-17 Mar-13 Apr-13 Frozen Component Usage May-13 Jun-13 Jul-13 Aug-13 Sep-13 Oct-13 Nov-13 Dec-13 Jan-14 Feb-14 Mar-14 Apr-14 May-14 Jun-14 Jul-14 Aug-14 Sep-14 Oct-14 MAT UK FFP Nov-14 Dec-14 Jan-15 Feb-15 Mar-15 Apr-15 May-15 Jun-15 MAT AB Neg Jul-15 Aug-15 Sep-15 Oct-15 Nov-15 Dec-15 Jan-16 Feb-16 Mar-16 Apr-16 May-16 Jun-16 Jul-16 Aug-16 Sep-16 Oct-16 Nov-16 Dec-16 Jan-17 Feb-17 Mar-17 Apr-17 Cryo Pools AB neg Moving Annual Total of Frozen Component Issues to Hospitals - 000s MAT FFP MAT Cryo Pools Moving Annual Total of UK non-mb FFP Issues to Hospitals - 000s

65 Indications for Use of Fresh Frozen Plasma Indication Codes 2016 Major haemorrhage early infusion of FFP Trauma 1 FPP : 1 RBC Other major haemorrhage settings a min. of 1 FFP : 2 RBCs Once bleeding is under control FFP use should be guided by coagulation tests as indicated below PT Ratio/INR >1.5 with bleeding PT Ratio/INR >1.5 and pre procedure Liver disease with PT Ratio/INR >2 TTP / plasma exchange Replacement of single coagulation therapy if no alterative available

66 No Justification for the Use of FFP Hypovolaemia Formula replacement Nutritional support Treatment of immunodeficiency states Reversal of prolonged INR in the absence of bleeding (in ICU manage patients with Vitamin K) Reversal of Warfarin treat with Prothrombin Complex

67 Indications For the Use of Cryoprecipitate Dose 2 pooled units (equivalent to 10 individual units) will raise fibrinogen by approx. 1g/L Cryoprecipitate is usually used with FFP unless there is an isolated deficiency of fibrinogen Use when Clinically significant bleeding and fibrinogen level <1.5g/L (<2g/L in obstetric bleeding) Fibrinogen <1g/L pre procedure Bleeding associated with thrombolytic therapy Inherited hypofibrinogenaemia if fibrinogen concentrated not available

68 Selection of FFP According to Recipient/Donor Blood Group Do we match for D? RECIPIENT S GROUP O A B AB 1 st choice O 1 A B AB 2 2 nd choice A AB 2 AB 2 A 3 3 rd choice B B 3 A 3 B 3 4 th choice AB Group O FFP must not be given to recipients of other ABO groups 2. AB plasma, though haemolysin free and suitable for patients of any ABO group, is often in short supply 3. Tested and found to be negative for high-titre ABO antibodies

69 Selection of FFP for Neonates BSH guidelines 2004/2005 also guidelines on transfusion for foetuses/neonates/older children (BCSH 2016) Group AB (or compatible with recipients ABO antigens) Infused in small volumes (Paedi FFP splits single exposure) Methylene blue treated

70 Choice of group of Cryoprecipitate according to recipient s ABO group Cryoprecipitate contains very little immunoglobulin and has never been reported to cause significant haemolysis AB cryoprecipitate availability is a low Group O 1 st choice O Group A 1 st choice A Group B 1 st choice B 2 nd choice A or B 2 nd choice O or B 2 nd choice O or A Group AB 1 st choice AB 2 nd choice A or B 3 rd Choice O Taken from the Handbook of Transfusion Medicine ed. Dr D Norfolk

71 Pathogen Inactivated FFP 2 main types Methylene Blue (MBFFP) Solvent Detergent (SDFFP)

72 Methylene Blue Treatment Patients born on, after 1/1/1996 or high usage adults European sourced, single unit male plasma, pathogen reduced Phenothiazine dye: inactivates enveloped viruses and bacteria by binding to and cross-linking DNA MB added to final conc of 1µM Exposed to white light for mins. MB removed by filtration (residual <0.05µg/ml) Active against most enveloped viruses Not active against intracellular viruses so plasma must be either frozen / thawed or filtered first Factor VIII/Fibrinogen - reduced concentration by 65-80% Content of clotting factors varies between individual packs 2012 withdrawn in France concerns about allergic reactions and fibrinogen concentrations

73 Solvent Detergent FFP Octaplas Recommended for plasma exchange in TTP Pooled product (up to 1520 plasma donations) sourced from countries with a low risk of vcjd Prion reduced version Octaplas LG now licensed in the UK UK licensed medicinal product SD process inactivates bacteria and most enveloped viruses Solvent disrupts the lipid membrane Detergent then added to inactivate viral contents Solvent and detergent removed (dissolved in oil) Genome testing done for non-enveloped viruses (Parvovirus B19, Hep A) Reduced concentration of fibrinogen and factor VIII by 15-20%

74 MB vs. SD Solvent Detergent Cheaper than MB Increased consistency of product Pooling dilutes out antibodies / allergens lower risk of allergic reactions, ABO transfusion reactions, TRALI Loss of approx. 15% fibrinogen and 20-30% Factor VIII Methylene Blue Single donation - lower risk of emerging pathogens Male sourced to reduce the risk of TRALI 20-30% decrease in fibrinogen and Factor VIII Variability of coagulation factors per bag Allergic risk the same as FFP

75 Other methods of Viral Inactivation Heat treatment inactivates non-enveloped viruses Psoralens - when added to a plasma product they intercalate with strands of nucleic acids Used for pathogen inactivation of platelet concentrates

76 Case Studies

77 Granulocytes Pooled Buffy Coat in Platelet Additive Solution Neutrophils are the major cellular component Manufactured by Pooling 10 buffy coats all with the same characteristics Removing red cells and plasma Resuspended in PAS and one male plasma A standard adult dose is 2 granulocyte pools (20 buffy coats) Contains 2.5 ADT of platelets Contaminated with red cells

78 Granulocytes Pooled Product MUST Irradiated Crossmatched D compatible Patient Group 1st Choice 2 nd Choice 3 rd Choice O O N/A N/A A A O HT neg N/A B B O HT neg N/A Storage 22 o C +/- 2 o C No agitation Use as soon as possible within 24hrs AB AB A (or B) HT neg O HT neg

79 Who Should Receive Granulocytes

80 Final RadTag Labels Key 1. Product Code 2. Indicator Type (Gamma or Xray) 3. Irradiator Indicator 4. Instructions 5. Barcode 6. Label Expiry Date 7. Lot Number 8. Min Gy target Un irradiated Label Irradiated Label NB: Please note that the post irradiation shade of blue may be different to that in the second image

81 Irradiated Products Renders any residual WBCs incapable of multiplying in the patient s bone marrow Reduces the risk of TA-GvHD Irradiation can be by Gamma Irradiation (Cesium-137) Minimum dose 25 Gy ray sensitive labels X-ray irradiation

82 Irradiated products PRODUCT Red cells Platelet concentrates Granulocytes IRRADIATION PROCESS May irradiate at any time up to 14 days after collection No restriction on the platelet age at the time of irradiation ASAP after production EXPIRY 14 days from date of irradiation (24 hours for intrauterine / exchange) Normal expiry time Normal expiry time

83 Specific Products IgA deficient products Panel of donors for patients with documented antibodies Red cells, FFP and platelets available Frozen Red Cells National frozen blood bank at Liverpool to support patients with rare antibodies Takes 8 hours to thaw, wash and transport blood Shelf life 24 hours open system 72 hours closed system International frozen banks available e.g, Europe, USA, South Africa