Human errors in manual techniques for ABO/D grouping are associated with potentially lethal outcomes.

AIMS/OBJECTIVES: To review if ABO/D grouping errors are more likely to occur with manual intervention compared to automation. BACKGROUND: Human errors in manual pre-transfusion testing may result in ABO/D-incompatible transfusions and catastrophic outcomes. Accurate ABO/D grouping is a critical part of pre-transfusion testing. METHODS: This was a retrospective analysis of reports made to Serious Hazards of Transfusion (SHOT) between January 2004 and December 2016 where ABO/D grouping errors led to the transfusion of an incorrect blood component to review if errors are more likely to occur with manual intervention compared to automation. RESULTS: In 148 of 158 (93%) ABO/D grouping errors, manual intervention took place. In the remaining 10, causes were not reported. No errors occurred with full automation. Interpretation errors occurred in 86 of 148 (58%) and 42 of 148 (28%) transcription errors, and in 20 of 148, wrong or no samples were selected. Of 148 errors, 21 (14%) resulted in ABO-incompatible transfusion, with one death in 2004 due to an interpretation error in a manual ABO group. In 30 of 148 (20%), D-positive red cells were given to D-negative recipients, where three women of child-bearing potential became sensitised and developed anti-D. ABO grouping errors have reduced from 18 of 539 (3%) of total reports analysed in 2004 (3·3%) to 3 of 3091 (0·10%) in 2016. CONCLUSIONS: Where manual testing cannot be avoided, results should be confirmed using automated techniques as soon as possible, and a back-up process should be available 24/7. SHOT data confirm that manual interventions are prone to human error, especially in transcription and interpretation, and demonstrate a continuing need for appropriate serological knowledge and understanding by transfusion laboratory staff to underpin safety provided by automation and information technology (IT).

Staffing in hospital transfusion laboratories: UKTLC surveys show cause for concern.

OBJECTIVES: To monitor minimum standards in hospital transfusion laboratories in relation to qualifications, training, competency and the use of information technology over time against published recommendations. BACKGROUND: The United Kingdom Transfusion Laboratory Collaborative was formed in 2006 with representatives from relevant organisations and has published standards for transfusion laboratory practice. The standards are set to ensure safe transfusion laboratory practice. Regular surveys are performed to see the extent to which laboratories are able to meet these standards and where any problems lie. METHODS: An electronic survey is sent to hospital transfusion laboratories on a single mid-week day in the spring and is repeated every 2 years from 2011, to be completed by the lead in transfusion for the day. The questions cover staffing, training, funding and workload. RESULTS: Transfusion laboratories are having difficulty with staffing, particularly recruitment of suitably trained biomedical scientists, and with funding and time for training and education. Laboratory errors reported to the Serious Hazards of Transfusion haemovigilance scheme (SHOT) have not decreased with time, related to the under-resourced workforce. CONCLUSION: Problems in laboratory staffing and expertise in hospital transfusion laboratories need to be urgently addressed. The transfusion laboratory provides a key service to hospitals. The Blood Services in England and Wales are developing supportive strategies.

International haemovigilance: what have we learned and what do we need to do next?

The International Haemovigilance Network (IHN) defines haemovigilance as 'a set of surveillance procedures covering the whole transfusion chain (from the collection of blood and its components to the follow-up of recipients), intended to collect and assess information on unexpected or undesirable effects resulting from the therapeutic use of labile blood products, and to prevent their occurrence or recurrence'. IHN, the International Society of Blood Transfusion and World Health Organization work together to support both developing and established haemovigilance systems. Haemovigilance systems provide valuable data on a range of adverse events related to blood donation and clinical transfusion, from donor syncopal events to transfusion-transmitted infections, immunological complications and the impact of human errors. Harmonised definitions for most adverse reactions have been developed and validated internationally. Definitions of pulmonary complications are again under review. Haemovigilance data have resulted in changes in policy, products and practice, and can complement and inform clinical audit and research, leading to improved blood donor safety, optimised product use and better clinical outcomes after transfusion. However, more work is needed. Not all countries have haemovigilance systems in place. More robust data and careful analysis are required to improve the understanding of the causes, occurrence and clinical outcomes of these events. Wider dissemination of results will facilitate health policy development internationally, and implementation of haemovigilance recommendations will support further important progress in blood safety.

Conference report: International Haemovigilance Seminar and the SHOT Annual Symposium, 10-12 July 2018.

The Annual SHOT Report was published on July 12 at the Annual Symposium. This was preceded by a 2-day meeting of the International Haemovigilance Network (IHN). The IHN meeting provides an opportunity for haemovigilance experts to network with one another and share presentations, which this year included those from China and Taiwan. Reviews of pulmonary complications were highlighted since the definitions of both transfusion-related acute lung injury and transfusion-associated circulatory overload are undergoing revision. The seminar provided an opportunity to present some UK data to an international group (the INTERVAL donor study, the value of big data and work on genomics and human factors). SHOT reports for incidents reported in 2017 demonstrate that, overall, 85·5% are caused by errors. Key recommendations from SHOT are: (i) All staff involved in transfusion must be trained in and know ABO group compatibility. Clinical staff must not just rely on the laboratory staff to get this right. (ii) IT systems have the potential to increase transfusion safety by minimising human factors and should be considered for all transfusion steps. (iii) A formal risk assessment for transfusion-associated circulatory overload should be undertaken wherever possible.

Serious hazards of transfusion - conference report: celebration of 20 years of UK haemovigilance.

The Annual SHOT Report for incidents in 2016 was published on July 12 and celebrated of 20 years of UK haemovigilance. Components are very safe, related in part to risk-reduction measures triggered by SHOT reporting. Transfusion-related acute lung injury is now very rare (all plasma components are provided from male donors), and infection transmission is also uncommon - a single transmission of hepatitis E in 2016 and no bacterial transmissions. Human factors (errors) account for 87% of all reports. Deaths and major morbidity most often result from transfusion-associated circulatory overload. Wrong transfusions and deaths from ABO-incompatible transfusion can be reduced by correct bedside checks. It is notable that information technology systems may not be safe. Standardisation is required for flags and alerts. SHOT key recommendations include: assess patients for transfusion-associated circulatory overload prior to transfusion. Be like a pilot - use a bedside checklist when setting up the transfusion.

Evaluation of the use of rotational thromboelastometry in the assessment of FXI deficency.

INTRODUCTION: The absence of a reliable clinical test to predict bleeding tendency leaves factor XI (FXI)-deficient individuals at risk of overtreatment or under treatment. AIM: To assess whether rotational thromboelastometry has value in detection of FXI deficiency and identification of bleeding tendency. METHODS: Thromboelastometry was measured in whole blood and platelet-rich plasma (PRP) samples containing corn trypsin inhibitor (CTI) from controls (n = 50) and FXI-deficient individuals (n = 93) at tissue factor (TF) 0.12 pm. The effect of tissue plasminogen activator was also assessed. For analysis, FXI-deficient individuals were divided into bleeders (n = 24) and non-bleeders (n = 44) based on experience of tonsillectomy and/or dental extraction prior to diagnosis. RESULTS: In whole blood, thromboelastometry distinguished those with major FXI deficiency (FXI:C ≤ 15 IU dL-1 ) but not partial deficiency from control populations, but did not identify bleeding phenotype. In PRP, bleeders had significantly longer clot formation time [CFT; 434 ± 179 s vs. 277 ± 70 s (mean ± SD); P < 0.05] and smaller α angle [43.8 ± 9.5° vs. 52.4 ± 5.8° (mean ± SD); P < 0.05] compared to non-bleeders. However, these parameters were found to depend on multiple additional variables and on an individual basis, ROC analysis showed test specificity for bleeding phenotype identification to be only 38.5% at 100% sensitivity: CFT (area under first derivative curve: AUC = 0.8091, P = 0.0014), α angle (AUC = 0.7804, P = 0.006). CONCLUSION: Thromboelastometry in PRP with CTI samples triggered with TF 0.12 pm was able to distinguish between bleeders and non-bleeders in FXI deficiency, but poor specificity restricts its clinical application as a test to identify bleeding phenotype. Further technical advances to the assay may allow better discrimination.

Evaluation of the use of global haemostasis assays to monitor treatment in factor XI deficiency.

INTRODUCTION: Previous guidelines recommend that FXI:C levels should be used to monitor FXI replacement in factor XI (FXI) deficiency. However, FXI:C levels do not correlate with bleeding tendency in this disorder and may not be the optimal test by which to monitor and determine further treatment in the postoperative period. AIM: To assess whether the thrombin generation assay (TGA) and rotational thromboelastometry can be used to monitor FXI replacement peri-operatively in FXI deficiency and to determine if changes in FXI:C levels correlate with changes in thrombin generation and clot formation parameters following treatment with solvent-detergent fresh frozen plasma (SD-FFP). METHODS: The TGA and rotational thromboelastometry were used to measure thrombin generation and clot formation in 11 adults with FXI deficiency who were treated with either SD-FFP (n = 8) or FXI concentrate (n = 3) as prophylaxis peri-operatively. Blood samples were taken pre- and 30 min post-treatment. RESULTS: Global haemostasis assays can be used to measure the effect of FXI replacement with SD-FFP or FXI concentrate in FXI deficiency. Both treatment types improved thrombin generation and clot formation. However, the remaining response to treatment at 24 h post SD-FFP was variable and changes in FXI:C levels were not predictive of changes in thrombin generation/thromboelastometry parameters after treatment with SD-FFP. CONCLUSION: Global haemostasis assays may provide a more reliable means of monitoring SD-FFP treatment with the potential to prevent individuals receiving unnecessary treatment, however, their clinical use in decision making needs to be tested in a larger prospective study.

SHOT conference report 2016: serious hazards of transfusion - human factors continue to cause most transfusion-related incidents.

The Annual SHOT Report for incidents reported in 2015 was published on 7 July at the SHOT symposium. Once again, the majority of reports (77·7%) were associated with mistakes ('human factors'). Pressures and stress in the hospital environment contributed to several error reports. There were 26 deaths where transfusion played a part, one due to haemolysis from anti-Wra (units issued electronically). The incidence of haemolysis due to this antibody has increased in recent years. Transfusion-associated circulatory overload is the most common contributor to death and major morbidity. Reports of delays to transfusion have increased, some caused by the failure of correct patient identification. There were seven ABO-incompatible red cell transfusions (one death) with an additional six to allogeneic stem cell transplant recipients. Near-miss reporting and analysis is useful and demonstrated nearly 300 instances of wrong blood in tube, which could have resulted in ABO-incompatible transfusion had the error not been detected. Errors with anti-D immunoglobulin continue, and preliminary data from the new survey of new anti-D found in pregnancy has shown that sensitisation occurs in some women even with apparently 'ideal' care. For the first time, the SHOT report now incorporates a chapter on donor events.

Are the 'rules' for times in set up and duration of red cell transfusion too strict?

OBJECTIVES: To discover if any adverse clinical effects have been reported to the UK haemovigilance scheme, Serious Hazards of Transfusion (SHOT) relating to delays in set up of transfusion or extended transfusion time for red cell units. BACKGROUND: Current guidance for duration of transfusion is based on outdated studies that do not reflect current UK Blood Service practices. Recent evidence suggests that the '30-min rule' could be extended without adverse effects. METHODS: Aggregated data from reports to SHOT covering a 5-year period (2010-2014) were reviewed in order to identify adverse clinical outcomes related to delay in set up of a red cell transfusion of more than 30 min after removal from cold storage, or total transfusion time of longer than 5 h. RESULTS: Five years of data from SHOT shows that there were no adverse clinical events related to delays in setting up transfusion or extended transfusion time between 2010 and 2014. There were a total of 382 reports which included 143 delays in set-up, and 239 episodes where transfusion took longer than 5 h. CONCLUSIONS: Delays in set up of transfusion and extended transfusion time did not result in any adverse clinical outcomes. Current guidance may be too stringent and lead to increased wastage.

In vitro comparison of the effect of two factor XI (FXI) concentrates on thrombin generation in major FXI deficiency.

INTRODUCTION: Bleeding risk in factor XI (FXI) deficiency following surgery may be reduced by treatment with either of two FXI concentrates, but indications for their use are unclear and treatment has been associated with thrombosis. AIM: To quantify and compare the effects of two different FXI concentrates on thrombin generation (TG) in major FXI deficiency (FXI:C < 15 IU dL(-1) ). METHODS: Thrombin generation was measured in controls (n = 50), FXI-deficient individuals pre and post in vitro spiking with FXI concentrates (n = 10), and in ex vivo samples following treatment with FXI concentrate (n = 3). RESULTS: Thrombin generation was significantly impaired in FXI deficiency but improved following FXI replacement in vitro and in vivo. LFB Hemoleven(®) had greater effect on TG than BPL FXI concentrate in vitro (equivalent in vivo doses 10, 20 and 30 U kg(-1) ): higher endogenous thrombin potential (ETP) (P < 0.0001), peak height (P < 0.01) velocity (P < 0.0002) and shorter lag time and time to peak (both P < 0.003). Some measurements with LFB Hemoleven(®) exceeded the reference range. At lower dose (5 U kg(-1) ), BPL FXI concentrate normalized all TG parameters and LFB Hemoleven(®) normalized the ETP but exceeded the reference range with other parameters. CONCLUSION: Both FXI concentrates improve TG in vitro in major FXI deficiency but differ in dose response, and for both products, doses lower than previously recommended normalized TG in vitro. Comparison of in vitro spiked and ex vivo samples suggest that in vitro results could be used to estimate an expected in vivo response to FXI replacement.

The natural history of occult or angiodysplastic gastrointestinal bleeding in von Willebrand disease.

Recurrent gastrointestinal bleeding is one of the most challenging complications encountered in the management of patients with von Willebrand disease (VWD). The commonest cause is angiodysplasia, but often no cause is identified due to the difficulty in making the diagnosis. The optimal treatment to prevent recurrences remains unknown. We performed a retrospective study of VWD patients with occult or angiodysplastic bleeding within the setting of the von Willebrand Disease Prophylaxis Network (VWD PN) to describe diagnostic and treatment strategies. Centres participating in the VWD PN recruited subjects under their care with a history of congenital VWD and gastrointestinal (GI) bleeding due to angiodysplasia, or cases in which the cause was not identified despite investigation. Patients with acquired von Willebrand syndrome or those for whom the GI bleeding was due to another cause were excluded. Forty-eight patients from 18 centres in 10 countries were recruited. Seven individuals had a family history of GI bleeding and all VWD types except 2N were represented. Angiodysplasia was confirmed in 38%, with video capsule endoscopy and GI tract endoscopies being the most common methods of making the diagnosis. Recurrent GI bleeding in VWD is associated with significant morbidity and required hospital admission on up to 30 occasions. Patients were treated with multiple pharmacological agents with prophylactic von Willebrand factor concentrate being the most efficient in preventing recurrence of the GI bleeding. The diagnosis and treatment of recurrent GI bleeding in congenital VWD remains challenging and is associated with significant morbidity. Prophylactic treatment with von Willebrand factor concentrate was the most effective method of preventing recurrent bleeding but its efficacy remains to be confirmed in a prospective study.

UK Transfusion Laboratory Collaborative: minimum standards for staff qualifications, training, competency and the use of information technology in hospital transfusion laboratories 2014.

The SHOT Adverse Incident Reporting Scheme has consistently reported an unacceptably high level of errors originating in the laboratory setting. In 2006 an initiative was launched in conjunction with the IBMS, SHOT, RCPath, BBTS, UK NEQAS, the NHSE NBTC and the equivalents in Scotland, Wales and Northern Ireland that led to the formation of the UK TLC. The UK TLC in considering the nature and spread of the errors documented by SHOT concluded that a significant proportion of these errors were most likely to be related to either the use of information technology or staff education, staffing levels, skill mix, training and competency issues. In the absence of any formal guidance on these matters, the UK TLC developed a series of recommendations using the results of two laboratory surveys conducted in 2007 and 2008.

Enhancing haemophilia care through registries.

Clinical registries or databases have an increasing role in the management of inherited bleeding disorders. Initially, research-based registries provided valuable data and now national databases are increasingly being developed with multiple stakeholders, including persons with haemophilia (PWH) and payers, to enable improvements and efficiencies in care. Registries are extending to international collaborations to collect adverse event data and comparisons of national approaches to the management of haemophilia to improve the availability of product to PWH.