Paula Bolton-Maggs Medical Director SHOT

Paula Bolton-Maggs Medical Director SHOT

Lancet April 30, 1983 The baby was transfused in March 1981 but there was reluctance by reviewers and publishers to publish rapidly NEJM: Confirmed link between transfusion and AIDS 28% of 2157 patients with AIDS had previously been transfused

Surveillance procedures from the collection of blood and its components to the follow up of the recipients To collect and assess information on unexpected and undesirable effects resulting from the therapeutic use of labile blood components And to prevent their occurrence or recurrence

Identify trends in adverse reactions and events Inform policy within transfusion services, DH, EU Target areas for improvement of practice Aid production of clinical guidelines for use of blood components Promote development of suitable education and training Identify and promote standards of practice Stimulate research and detailed audit Raise awareness of transfusion hazards and their prevention Be an early warning of new complications Improve safety of transfusion for patients

In 1990s - growing awareness of safety issues in blood transfusion especially HIV, HCV, hospital errors (McClelland BMJ 1994;308:1205) Incidence of major complications of blood transfusion was unknown Working group set up in 1994 to consider haemovigilance SHOT launched 1996 SHOT report first published for 1996-1997 data Increasing number of reports each year Evolution of new categories reflecting reports 17 th report (2013 data) published July 2014

Professionally led scheme providing analysis of anonymised data by experts in each area of reporting Regular output in annual report, papers, meetings Recommendations for actions made to CMOs, DH, hospitals, professional bodies and blood services Measurable impact on patient safety Reduction in transfusion-related acute lung injury (TRALI) Reduction in ABO incompatible transfusions Reduction in bacterial contamination

Hospital transfusion teams Consultant haematologist Laboratory manager Transfusion practitioner On-line reporting system Categories Follow up with incident investigation Annual reports www.shotuk.org

The European Directive 2002/98/EC Blood Safety and Quality Regulations 2005 To set high standards of quality and safety for the collection, testing, processing, storage and distribution of human blood and blood components To reassure the public that human blood and components, which are derived from donations in one member state, meet the same requirements as those in their own country

UK Blood Safety and Quality Regulations (BSQR) 2005 (SI 50) Became law Nov 2005 MHRA became the competent authority

All serious adverse reactions same as for SHOT All serious adverse events signalling a process failure in the Quality Management System (QMS) occurring within the responsibility of the Blood Establishment or the Hospital Blood Bank, regardless of whether the component was transfused (SHOT reportable if transfused) Adverse events involving only clinical staff are not reportable to MHRA, but are reportable to SHOT, comprising the largest sub-group of SHOT reports

Competent Authority appointed by DH to implement new legislation and as regulator product quality and safety compliance with requirements for QMS Legal requirement to send numbers of SAEs and SARs to EU annually first year of mandatory reporting 2008 (June) May impose sanctions and demand corrective actions on individual sites not analysing trends or making recommendations

MHRA Medicines and Healthcare Products Regulatory Agency Competent Authority for the BSQR 2005 QMS in blood establishments and hospital blood banks Competent Authority for the Medicines Act 1968 Competent Authority for the Medical Devices Regulations 2008 STATUTORY reporting SHOT Serious Hazards of Transfusion Confidential enquiry Serious adverse reactions/events AND near misses all of which occur in BOTH a laboratory and CLINICAL environment PROFESSIONALLY MANDATED reporting

Decision to transfuse Prescription/request Sampling for pre-transfusion testing Laboratory testing Collection of blood from issue fridge Bedside administration Monitoring the patient

SHOT since 1996 set standards in EU and beyond BSQR implemented from November 2005 adverse event reporting to EU mandatory SABRE web based reporting to MHRA 2005 Web-based reporting to SHOT 2010 Initial data entered via SABRE to link case numbers

So what is the greatest risk of transfusion

SHOT Cumulative data: 17 years n=13141 Transfusion reactions which may not be preventable Possibly or probably preventable by improved practice and monitoring Adverse events due to mistakes

+ Errors 77.6%

Incorrect blood component transfused Where are the mistakes made? Clinical errors Laboratory errors Copyright SHOT 2014

Incorrect blood component transfused Data from 220 reports 547 errors Copyright SHOT 2014

Incorrect blood component transfused Data from 220 reports 547 errors The common combinations of three: 78% request, prescription and administration 12% collection, prescription and administration Copyright SHOT 2014

Identification Documentation Communication Copyright SHOT October2014

Outcome of ABO incompatible red cell transfusions 66% have no adverse effect 15 deaths to 2005 BSQR 4 deaths 2006-2013 NPSA SPN 14 Competency assessments Copyright SHOT 2014

Immediate and life-threatening : ABO incompatibility; anaphylaxis Hours: pulmonary complications, bacterial infections, transfusion reactions Days: Haemolytic reactions Late (months or years): viral infections; iron overload

Transfusion reactions may have many overlapping symptoms and signs with varying severity Fever, chills, rigor, myalgia, nausea, urticaria, itching, swelling, respiratory symptoms...etc. Advise patients to report any adverse events in 24 hrs after transfusion

A 56 year old man with acute myeloid leukaemia is having a platelet transfusion 5 minutes into the transfusion he feels unwell His temperature has increased to 40 o C He is sweating with severe hypotension

(Choose 1) 1. Allergic reaction 2. Haemolytic reaction 3. Infection in central venous line 4. Infection in platelet bag

ABO incompatibility Contact laboratory immediately Bacterial infection Central and peripheral blood cultures Start broad spectrum antibiotics Inform laboratory and haematologist to arrange culture of the unit Inform the Blood Service

Stop the transfusion, maintain IV access with saline and check the bag and patient ID Rapid medical assessment Inform the transfusion laboratory Blood culture and return blood bag to lab Renal function Monitor fluid balance (input and output) Collect first and subsequent urine samples

Correct patient identification is vital Patient Blood Component Sample Testing

Diagnosis and identification of possible need to transfuse Decision to transfuse Phlebotomy for group and crossmatch Written request to lab for blood Written prescription/order/authorisation for transfusion Laboratory testing, component selection and issue Collection from issue site Bedside checking of patient, unit ID and administration Monitoring/observing and noticing adverse event or reaction Appropriate management of adverse event or reaction

Transposed patient ID during phlebotomy leads to ABO incompatible transfusion Patient A, blood group O RhD negative, was transfused 2 units of A RhD positive blood during cardiac surgery On arrival in ICU he received two more group A units without apparent adverse events. Following transfusion, the patient showed evidence of haemolysis, with a fall in Hb requiring further transfusions, and rise in bilirubin to 241mmol/L within 6 days He had an extended stay in ITU.

Patient A and patient B were sampled at the same time in a preoperative clinic. The nurse was distracted while bleeding patient A, did not complete the process at the bedside, and so patient details were transposed when labelling the samples. Near Miss: Patient B s mislabelled sample was detected in the laboratory, because a historical group was available. Adverse event: Patient A had no historical group and the error was not detected.

Why did it happen? What can be learned from it? Corrective and preventive actions to reduce likelihood of recurrence

A child with beta thalassaemia major, blood group O, receives 3 ml of an incompatible unit of blood group A Recognised early, stopped, no harm done, but kept in hospital overnight for observation Blame culture dreadful deed, sack the nurse No-blame culture- understand the circumstances which led to this and take action to prevent recurrence

(James Reason, 2004)

Likelihood multiplied by the consequence gives a RISK SCORE

She did not intend to make this mistake but it could have resulted in death, and was very likely to happen again, so was treated as a very serious incident with a high risk score Likelihood multiplied by the consequence gives a RISK SCORE

The nurse was working alone in the day unit Three people needed transfusions she collected all three units at the same time She borrowed a nurse from the next ward to check all three, putting each down on a table beside the patient She was using aseptic technique to access the portacath, and the second nurse handed her the wrong unit which was not checked again at the bedside Incident recognised when next unit put up with bedside check

Key Root Cause: Collection of three units at the same time, and later failure to do the final bedside check immediately prior to transfusion The nurse was working alone in the day unit The staff were accepting a culture of chronic understaffing audit Three showed people solo working needed 75% transfusions of the time. Lone working she was collected also all three associated units with at a poor the record same (42%) time of correct observations during transfusion. As a result of this investigation, an addition member of She staff borrowed was employed nurse from the next ward to check all three, putting each down on a table beside the patient She was using aseptic technique to access the portacath, and the second nurse handed her the wrong unit The which layout was of the day not unit checked was reviewed again and changed at the bedside Incident recognised when next unit put up with bedside check The transfusion training of both nurses was out of date, and she forgot that collection of more than one unit at a time was against policy but also it was difficult to get away from the ward on three separate occasions while working alone So, the RCA resulted in several SOLUTIONS to improve the system

An elderly male patient received the first unit of FFP to correct a coagulopathy Half-way through the unit, he developed marked hypotension (from 100/60 to 50/20) and a widespread urticarial rash and shortness of breath with wheeze

(Choose 2) 1. Discontinue the transfusion 2. Continue the transfusion more slowly 3. Give hydrocortisone and piriton 4. Give adrenaline 5. Try a different unit

Allergic or anaphylactic reactions are unpredictable and usually occur early This is why all patients having blood products must be monitored Adrenaline (IM) is the treatment of choice and should be available in all areas where transfusions take place

Minor reactions excluded

Life threatening Requires immediate intervention Intramuscular adrenaline Support the airway (oxygen) Longer term: discuss with immunologist how to manage future transfusions See BCSH guidelines on acute transfusion reactions www.bcshguidelines.com

An elderly woman with cirrhosis, ischaemic heart disease and a coagulopathy had an elective knee replacement She was transfused with 2 units FFP and 2 doses of platelets to cover removal of lines and epidural 30 mins after completing the transfusion she became suddenly breathless and hypoxic with signs of heart failure

The CXR showed bilateral shadowing and she was known to have impaired left ventricular function

(Choose 1) 1. TACO (transfusion-associated circulatory overload) 2. Chest infection 3. Acute myocardial infarction 4. TRALI (Transfusion-associated acute lung injury)

Consider TRALI or TACO Check airway and give oxygen Get expert medical assessment CXR and oxygen saturation

Acute dyspnoea with hypoxia and bilateral pulmonary infiltrates during or within 6h of transfusion, not due to circulatory overload or any other likely causes. Most suspected cases are complex Need expert panel assessment Serology: find anti-leucocyte antibodies in donor which react with recipient neutrophil antigens

Important cause of transfusion-related mortality and major morbidity Caused by HLA/HNA abs main source is donor plasma: A donor with a history of transfusion A female donor with a history of pregnancy abs in 10-15%

She was ventilated for 5 days and made a full recovery She was also treated with diuretics and IV fluids She was investigated for TRALI and this was confirmed by serological evidence of concordant HLA antibodies in one female donor of the apheresis platelets

TRALI relative risk from different components 1996-2003 Red cells Cryo FFP Platelets TRALI cases 33 2 31 27 Components issued 18,370,000 634,000 2,515,000 1,842,000 Risk/ component issued Relative risk compared to red cells 1:556,000 1:317,000 1:81,000 1:68 000

Decision to use male donors for FFP

TACO is much more common than TRALI and it can be difficult to confirm the cause of acute respiratory symptoms Elderly patients are particularly at risk of TACO Even small transfusions may be enough All patients need careful monitoring and appropriate investigation

(unsatisfactory definition) Any 4 of the following occurring within 6h of transfusion Acute respiratory distress Tachycardia Increased blood pressure Acute or worsening pulmonary oedema Evidence of positive fluid balance

TRALI TACO Type of component Usually plasma or platelets Any BP Often reduced Often raised Temperature Often raised Normal Echo Normal Abnormal Diuretics Worsen Improve Fluid loading Improves Worsens

An 83-year-old male with refractory anaemia related to CRF received 2 units of RBCs, each over approximately 1.5 2.5 hours. He had continuing bradycardia during the second unit. He remained stable, but the bradycardia persisted at 40 45 bpm. Within 15 minutes of the start of the 3 rd unit of RBC, he became unresponsive with no cardiac output. Resuscitation was ultimately unsuccessful. A post-mortem examination showed acute LVF, hypertensive heart disease with mitral valve prolapse and hypertensive nephropathy. TACO following RBC transfusion to elderly male with renal impairment and cardiac failure

May need investigation in similar way Sustained rise in temperature and/or other systemic symptoms (chills, myalgia, nausea) may indicate bacterial infection or haemolysis Management may include antihistamines, oxygen etc.

A woman with Hb SC was transfused 2 units of red cells after an emergency caesarian section 10 days later she presents with Hb 67g/L, fever hypoxia and pain

(choose 1) 1. Sickle cell crisis 2. Delayed haemolytic transfusion reaction 3. Bacterial infection 4. Pulmonary embolism

She underwent exchange transfusion for sickle crisis but still had symptoms The Hb dropped below pre-transfusion levels with evidence of haemolysis noted on the blood film

1. None (choose any that are relevant) 2. Pre and post-transfusion samples for group and antibody detection 3. Direct antiglobulin test 4. Recheck cross match 5. Eluate of pre and post-exchange samples

DAT positive with anti-jk a detectable in eluate on pre- and post-exchange samples Four out of six units for exchange transfusion were Jk(a+) The anti-jk a became detectable in the plasma after a couple of days

Delayed transfusion reactions in sickle patients may be confused with sickle crises Antibodies may only be detectable by washing them off the red cells (eluate) Sickle cell disease patients are at particular risk of alloimmunisation and missed special requirements because clinicians forget to tell the lab

Young woman with history of multiple transfusions admitted with Hb 78g/L Transfused 7 d earlier; raised bilirubin and creatinine on this admission Anti Fy b found now in addition to previously known anti s Two Fy(b-) s- units transfused but during 2 nd unit she had rigors and respiratory arrest

ITU admission for a week Investigation: new weak anti-jk a by enzyme only Both units were Jk(a+) as were 2 of the 4 transfused 7 d before Acute and delayed HTR

Symptoms Fever >2 o C rise or >39 o C Investigations Standard plus repeat compatibility testing, DAT, LDH and haptoglobin Blood cultures from patient Coagulation screen Do not discard unit Sustained fever: return unit to lab, repeat antibody screen and DAT NB. Standard investigations for all transfusion reactions FBC, renal and liver function, assessment of urine for haemoglobin

Symptoms Mucosal swelling Dyspnoea, wheeze or features of anaphylaxis Hypotension (isolated fall systolic of > 30mm resulting in level > 80mm Investigations Standard, plus IgA If <0.07g/L and no general hypogammaglobulinaemia confirm and look for IgA antibodies Standard, plus oxygen saturation/blood gases, CXR; Investigate as for fever If allergy suspected, IgA

Definition: sudden onset of thrombocytopenia occurring 5-12 d following red cell transfusion associated with antibodies in the patient directed against human platelet antigen systems. Commoner in women, rare (1-2 pa) Management: IVIg Women are at risk of neonatal alloimmune thrombocytopenia in future pregnancies

Category Risk per components issued Total risk of death (including probable cases) 1 in 125,000 Total risk of major morbidity 1 in 19,157 Risk of death from error 1 in 454,545 Risk of major morbidity from error 1 in 196,078 Risk of death from TACO 1 in 227,273 Risk of major morbidity from TACO 1 in 81,3000 Risk of major morbidity from ATR 1 in 36,764 Category HBV HCV HIV Risk of infected donation entering blood supply 1 in 1.3 million 1 in 28.6 million 1 in 7.1 million

Viral infections Identify and report Establish link with previous transfusion Counselling and management Iron overload Think of this in any chronically transfused patient and do regular assessment of iron loading May be missed in young patients undergoing cancer chemotherapy?

ADU IBCT PTP ATR HTR 1 Inappropriate and 5 delayed transfusions 1 ABO incompatible transfusion 1 Post-transfusion purpura 2 Acute transfusion reactions 3 Haemolytic transfusion reactions TRALI 2Transfusion-related acute lung injury TACO 20 Transfusion-associated circulatory overload (n=39) Unclassifiable 3-2 infants with necrotising enterocolitis and 1 adult after IVIg TA-GvHD 1 transfusion-associated graft versus host disease

Fludarabine introduced for CLL induces profound lymphopenia TA-GvHD cases reported in 1993, 1994, 1996 Guidelines for irradiated blood components 1996 (latest update 2010) B cell diseases are not an indication on their own for irradiated products

Omission of irradiation in 999 patients at risk Many cases missed in patients who have received fludarabine Leucodepletion is protective

Patient group Number Treatment with purine analogues 178 Hodgkin lymphoma 68 Haemopoietic stem cell transplants 44 Others 99

Reasons for failure to provide irradiated components Haematology clinical staff forget/fail to inform the transfusion laboratory Need for irradiation overlooked when patient is admitted to a different specialty or hospital Need for irradiation is forgotten when historical (e.g. HD, fludarabine many years before) Immune deficiency not recognised (CVID, Di George syndrome) Overlooked in infants needing later top-up transfusion after intrauterine or exchange transfusion

UK Transfusion Laboratory Collaborative 2009 BCSH Guidelines

NPSA SPN14 Right patient, right blood competency assessment NPSA SPN11 Patient identification Wristbands SPN 24 NPSA RRR 17 Transfusion in an emergency Better blood transfusion initiatives DH circulars Working group set up to discuss national strategy for haemovigilance SHOT launched Start of NPSA NBTC National comparative audit programme UKTLC 1993 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 Figure 1

A programme of clinical audits looking at use and administration of blood and blood components in England and N Wales Funded by the NHSBT Started 2003, in collaboration with the clinical standards unit of the RCP http://hospital.blood.co.uk/safe_use/clinical_audit/national_comparative/index.asp

Identification Documentation Communication

Further information available: http://www.shotuk.org/ Educational resources Category definitions Annual Reports (including key to abbreviations) http://www.mhra.gov.uk/

Hazel Tinegate and the transfusion task force of the BCSH for ATR guidelines Hospitals for reporting cases to SHOT SHOT experts and incident specialists