Blood Transfusion - Safety, optimisation & new advances

Dr Shubha AllardConsultant Haematologist

Barts Health NHS Trust and NHS Blood and Transplant

NHS Blood and Transplant

• NHS Blood and Transplant (NHSBT) manages the national voluntary donation system for blood, tissues, organs and stem cells

• Supplies around 2 million units of blood a year

Blood safety/ Transfusion safety

SAFE TRANSFUSION

PROCESS

SAFE BLOOD COMPONENT

Blood Transfusion -Guidance and Regulations

• WHO recommendations• safe and adequate blood supply• also clinical transfusion process

– Appropriate use of blood– Collection samples, patient ID– compatibility testing– Administration of blood – Adverse event reporting– Hospital transfusion committee

• ‘Better Blood Transfusion’• EU Optimal Blood Use manual• (www.optimalblooduse.eu)

• Council of Europe• 47 member countries

European Union Blood Directives

• Setting standards of quality and safety for collection, testing, processing, storage and distribution of human blood and blood components

• Blood Safety and Quality Regulations 2005– Transposed into UK law

• Regulations affect the blood services (called blood establishments) and hospital transfusion laboratories (hospital blood banks)

• Competent Authority– Medicines and Healthcare products Regulatory Agency (MHRA)

Blood safety and Quality Regulations impact on hospitals in the UK

• Quality management system• Stringent requirements storage/distribution blood -‘cold chain’• standard operating procedures (SOPs)• Corrective and preventative action (CAPA)• Validation & change control

– Traceability– Training and competency assessment– Haemovigilance

• annual statement of compliance to MHRA

• ~60 hospitals inspected per year– ‘Cease & desist’– Critical non -compliances

Safety of the Blood Supply

• Voluntary and non-remunerated donor

• Donor Health Questionnaire

• Council of Europe - Mandatory screening tests– Hep B, Hep C, HIV 1 & 2– Additional testing – Syphilis, HTLV– Selective screening – Malaria, CMV

Infective risks - UK

Infection Testing started

Approximate risk of infection per

unit of blood in UK

Hepatitis B 1975 1 in 1.06 million

HIV 1985 1 in 6 million

Hepatitis C (Anti HCV and NAT testing)

1991 &1998

1 in 72 million

Health Protection Agency

Viral tests in blood donors

www.coe.int

Management chronic viral hepatitis in thalassemia: recommendations of an international panelMarco et al Blood 2010 116 2875

Hep C antibody in thalassemia patients

Ref no.Anti-

HCV+ %13 2006 Iran 732 19.314 2006 Turkey 399 4.415 2003 Thailand 104 21.216 2002 Lebanon 395 1417 2001 India 104 2118 Malaysia 85 22.421 2006 Iraq 559 67.322 Pakistan 35 6023 Italy 1481 85.224 Bahrain 242 20.525 Brazil 32 46.826 Hong Kong 99 34

27 UK 73 23.3

Wonke B et al Clin Pathol 1990;43:638

23.3% of 73 patients positive

Thompson et al 2011 Brit Journal of Haematol, 153, 121–128 Thalassemia Clinical Research Network Investigators:169 of 697 Hep C Ab pos – 24%

Cunningham et al 2004 Blood 104, 345% patients aged<16yrs23% aged 16-24yrs; 70% aged 25yrs or older

1998

West Nile Virus (WNV)• Flavivirus• Most cases asymptomatic • very mild short term symptoms (20%

infections)• 1% encephalitis/meningitis; can be fatal• First identified 1937 W Nile area Uganda• widely distributed Africa, West Asia,

Europe & Australia; US since 1999

transmission may occur as a result of blood donation

WNV – blood donation• EU Directive - deferral for 28 days - No provision for WNV

Nucleic acid testing (NAT) in place of deferral

• Since 2005 UK blood services have deferred travellers– Concerns re impact on blood supply – planning 2012 Olympic s– MHRA accepted WNV NAT testing rather than donor deferral– May- Aug 2012 NHSBT has tested ~13,000 donations - so far all

negative

• West Nile Virus and Blood Safety Introduction to a Preparedness Plan in Europe– EU satellite meeting Working Group on Blood Safety; Jan 2011– Surveillance, Risk assessment, Deferral criteria, NAT testing,

Impact on blood supply

Variant CJD• First noted in 1996

• Distinct from sporadic CJD• Median age at presentation 26 years• Neuropsychiatric symptoms, ataxia,

dementia.• Progression over 6 -40 months

same strain of prion disease as Bovine Spongioform Encephalopathy (BSE)

• 173 cases in UK

• 4 transfusion related cases• I case in Haemophilia patient

National Creutzfeldt-Jakob Disease Survellance Unit

(NCJDSU) www.cjd.ed.ac.uk

Red Cells Whole Blood Platelets (also apheresis) Fresh Frozen Plasma

Plasma Cryoprecipitate Paediatric FFP

Paediatric Cryo Fractionation

Factor concentrates egFVI I I , FI Xs

SD plasma I mmunoglobulin

Albumin, Anti D (Universal leucodepletion (Non UK Plasma) in UK since 1998)

Impact of nVJD on processing Blood Components UK

Blood processing – red cells

• Most of the plasma is removed

• Optimal Additive Solution added - SAGM in UK

• Red Book Specifications• Vol = 280+ 60ml• WBC < 5 x 106 /unit• Hct 0.5 - 0.7

• 35 day shelf life• For haemoglobinopathy

• Top up <14 days• exchange (SCD) <7 days

• (washed red cells)

Serious Hazards of Transfusion

(SHOT)

• UK-wide, established1996 confidential reporting

• evidence base to support – blood safety policy decisions– clinical guidelines & education– improvements in transfusion practice

Trend in total reports and total deaths definitely due to transfusion Trend in total reports and total deaths definitely due to transfusion

Special requirements Haemoglobinopathy

• TIF Guidelines, UK Standards thalassaemia, Sickle Cell Disease• British Committee Standards Haematology (www.bcsh.org)

• Red cells matched for Rh (D, C, c, E, e) and K antigens

• Antigen negative for current or historical red cell antibodies that are clinically significant

• patient’s red cells phenotyped prior to transfusion or molecular genotyping if transfused– C, c, E, e, K, k, Jka, Jkb, Fya, Fyb, MNS

Special requirements Haemoglobinopathy

• SHOT UK 2011 lessons - avoidable events

• Alloimmunisation SCD 20–35% or higher• Risk haemolytic transfusion reactions• Multiple & complex antibodies can result in

significant delays in sourcing blood• Autoantibodies

• Thompson et al 2011 Brit J Haem 153, 121– Red cell alloimmunization diverse popn of

transfused patients with thalassaemia

• 697 patients 16.5% allo and 5% auto abs

Anti-E 22 (19%)Anti-K 21 (18%)Anti-C 11 (9%)Anti-Kidd 9 (7%)Anti-HLA 8 (6%)Anti-c 7 (6%)Anti-e 6 (5%)Anti-Kpa 6 (5%)Anti-Lewis 4 (3%)Anti-D 4 (3%) Anti-S 3 (2%)Anti-V 2 (1%)Anti-Duffy 2 (1%)Anti-M 2 (1%)Other* 9

Thompson et al 2011 Brit J Haematol 153, 121

• SP-ICE: Anti body Database– Sharing information

• Increase in blood donations from ethnically diverse groups

• Rare blood units frozen

• International Rare Donor Panel, IBGRL, Bristol, UK -worldwide collaboration 5000 donors, 28 countries

frequency (%Blood group CaucasAfricanian African

Rh D 85 92 C 70 30 E 30 19 Kell K 9 2 Kidd Jka 77 92 Jkb 74 49

Duffy Fya 66 10 Fyb 83 23

Blood Group

AfricanCaucasian

Frequency %

NHSBT – a focus on improving care for haemoglobinopathy

patients

Molecular techniques - Extended red cell matching

• Automated, high throughput testing platforms – now available for molecular testing

• ?scope for extended donor testing and greater red cell antigen matching with recipient

• NHS Blood and Transplant - Evaluation of chip based and Luminex based genotyping platforms

– Panel of 1,000 DNA samples from donors with known phenotype

– Inter platform discrepancy very low (0.04%) across >20,000 blood groupings

– Pilot H&I and RCI labs implementation patient testing

Red cells from stem cellsHarvey G. Klein. Brewing bloodBlood 2011 118, 5069

Standardisedwell characterised, readily available red cells?

Culture systems to generate erythroid cells in laboratory from •Somatic stem cells•Embryonic stem cells•Induced pluripotent stem cells

Ex vivo production of human red cells, the Holy Grail of blood transfusion. illustration by Debra T. Dartez.

Blood safety, optimisation and new advances

• Transfusion transmitted infections– Reduced rates, never zero risk, emerging infections

• Adherence to guidelines– avoidable alloimunisation

• Haemovigilance– Essential for improving transfusion safety– Highlights areas for action

• New advances– e.g. IT, molecular techniques, pathogen activation