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.

Direct costs of transfusion reactions - an expert judgement approach.

BACKGROUND AND OBJECTIVES: Despite increasingly meticulous haemovigilance reporting throughout the world, a systematic assessment of the cost of transfusion reactions is still lacking. This is partly caused by the fact that such an assessment requires a subjective expert assessment of the additional costs linked to the adverse reaction. Data on the cost of transfusion reactions could support decision-making regarding blood transfusion safety measures. MATERIALS AND METHODS: Thirteen experts from nine hospitals were asked to estimate the additional care required following various types of transfusion reactions. Additional care was quantified as the proportion of reactions requiring care, and the amount of care required (e.g. hospitalization days, additional physician's time). Experts were also asked to provide, per type of transfusion reaction, an estimate of the proportion of transfusion reactions preventable. Structured quantitative expert elicitation methods were applied to obtain and combine expert estimates. RESULTS: The estimated annual in-hospital cost of transfusion reactions in the Netherlands is €933 356 per year (€1.52 per transfusion). Two-thirds (64%) of these are incurred by non-serious transfusion reactions. Circulatory overload, TRALI and anaphylaxis clearly dominate the costs of serious adverse transfusion reactions (66% in total); non-haemolytic transfusion reactions incur 46% of the cost of non-serious transfusion reactions. Additional safety measures targeting circulatory overload and new antibody formation potentially offer the highest cost reduction. CONCLUSION: In-hospital costs of transfusion reactions are substantial but contribute to less than 1% of the total cost of transfusion in the Netherlands. A considerable part of these costs (24%) might be preventable.

Donors' health state the year after peripheral haematopoietic progenitor cell collection: A prospective follow-up study in related and unrelated donors compared to first-time platelet donors.

Granulocyte colony-stimulating factor (G-CSF) mobilized peripheral haematopoietic progenitor cells collected by apheresis (HPC-A) are the most common source used for allogeneic hematopoietic stem cell transplantation (HSCT). Retrospective short and long-term donor follow-up studies show very low risks of serious complications and do not report compelling evidence of increased cancer occurrence. Some studies reported a prolonged period of leucopenia without an obvious association with infectious complications. However, beyond the first few weeks after the procedure a relationship between events is elusive. We therefore evaluated medical service utilization by prospectively recruited HPC-A donors and first-time platelet apheresis donors for comparison for 1 year after donation. Data were prospectively collected using questionnaires and by medical record review. A total of 215 HPC-A donors (111 unrelated donors and 104 related donors) and 96 first-time platelet donors consented to participation in the study. Follow-up was available for 202 (96%): questionnaires were returned by 74% and records from nonstudy contacts were available for 94% of donors. During the 1-year follow-up, 94 of the donors who returned questionnaires sought medical attention for diagnostic evaluation and/or treatment: 41% of HPC-A donors and 40% of platelet donors. Medical service utilization the first year after HPC-A donation is similar to that after first-time platelet donation. The occurrence of serious medical conditions in both related and unrelated HPC-A donors underscores the importance of participation in long-term follow-up in large cohorts. The findings in this relatively small cohort contribute to evidence on the safety of G-CSF mobilization and HPC-A. J. Clin. Apheresis 31:523-528, 2016. © 2015 Wiley Periodicals, Inc.

Presence of medication taken by blood donors in plasma for transfusion.

BACKGROUND AND OBJECTIVES: The TRIP national hemovigilance and biovigilance office receives reports on side-effects and incidents associated with transfusion of labile blood products. Anaphylactic reactions accounted for the largest number of serious transfusion reactions in the period 2008-2012. In most cases, no cause is found for these reactions. TRIP data show that anaphylactic reactions occur relatively frequently with transfusion of plasma or platelet concentrates. Data from blood services show that 10% or more of plasma donors regularly use medication which is permitted under donation guidelines. It is conceivable that medication taken by the donor in plasma for transfusion could cause an anaphylactic transfusion reaction in the recipient. This exploratory study investigated the presence of drugs or drug metabolites in donor plasma. MATERIALS AND METHODS: Samples (5 ml) were taken from thawed, quarantine fresh frozen plasma units (FFP) which had to be rejected for transfusion because of leaks or length of time after thawing. The samples were analysed for approximately 1000 drugs and drug metabolites using a toxicological screening method. RESULTS: Eighty-seven samples were analysed. Toxicological screening was positive in fourteen samples (16%). In eleven samples, one substance was found, and in three samples, the presence of two or three drugs was detected. CONCLUSION: After freezing, storage and thawing of fresh FFP, it is possible to detect medication taken by the donor. Further investigation is recommended to analyse whether donors' medication in plasma can be implicated in some cases of allergic or anaphylactic reactions in transfusion recipients.

Quality indicators for the hospital transfusion chain: a national survey conducted in 100 dutch hospitals.

BACKGROUND: The 2011 Dutch Blood Transfusion Guideline for hospitals incorporates seven internal quality indicators for evaluation of the hospital transfusion chain. The indicators aim to measure guideline compliance as shown by the instatement of a hospital transfusion committee and transfusion safety officer (structural indicators), observance of transfusion triggers and mandatory traceability of labile blood components (process indicators). STUDY DESIGN AND METHODS: Two voluntary online surveys were sent to all Dutch hospitals for operational years 2011 and 2012 to assess compliance with the guideline recommendations. RESULTS: Most hospitals had a hospital transfusion committee and had appointed a transfusion safety officer (TSO). In 2012, only 23% of hospitals complied with the recommended minimum of four annual transfusion committee meetings and 8 h/week for the TSO. Compliance with the recommended pretransfusion haemoglobin threshold for RBC transfusion was achieved by 90% of hospitals in over 80% of transfusions; 58% of hospitals measured the pretransfusion platelet count in over 80% of platelet transfusions and 87% of hospitals complied with the legally mandatory traceability of blood components in over 95% of transfusions. CONCLUSION: With the current blood transfusion indicators, it is feasible to monitor aspects of the quality of the hospital transfusion chain and blood transfusion practice and to assess guideline compliance. The results from this study suggest that there are opportunities for significant improvement in blood transfusion practice in the Netherlands. These indicators could potentially be used for national and international benchmarking of blood transfusion practice.

Quality validation of data in national haemovigilance systems in Europe: report of a survey on current state of practice.

European Union member states must have national haemovigilance reporting of serious adverse reactions and events. We sent national competent authorities an email questionnaire about data validation. Responses were received from 23/27 countries. Nine previously had no national haemovigilance system. In 13 (57%), the serious adverse reactions and events can be verified. Coverage of blood establishments is documented in 20 systems (87%) and of hospitals in 15 systems (65%). Although all member states have implemented haemovigilance systems, there are currently wide variations in data quality assurance, not allowing comparisons between countries.

Variation between hospitals in rates of reported transfusion reactions: is a high reporting rate an indicator of safer transfusion?

BACKGROUND AND OBJECTIVES: It has been suggested that the rate of reported transfusion reactions is positively correlated with safety of the transfusion chain in a hospital. We evaluated this assumption in the Transfusion Reactions in Patients Dutch National Hemovigilance Office database taking reported incorrect blood component transfused as a proxy for unsafe transfusion. METHODS: Reports from 2006 to 2010 and annual numbers of transfused blood components from the 103 hospitals were analysed. The rate of transfusion reactions per 1000 blood components was calculated per hospital. Logistic regression analysis was performed between reporting of at least one incorrect blood component and tertile of transfusion reaction rate. RESULTS: Out of the 103 hospitals, 101 had complete data in some and 93 in all 5years. In all, 72 had reported at least one incorrect blood component transfused; this was associated with blood use level and also with rate of reported transfusion reactions: odds ratio 4·2 (95% confidence interval, 1·3-13·7) in the highest vs. the lowest tertile after adjustment for blood use level. CONCLUSION: Hospitals in the Netherlands which report more transfusion reactions per 1000 units are also more likely to have reported incorrect blood component transfused. The data do not support that hospitals with a higher rate of transfusion reaction reports are safer.

Allo-exposure status and leucocyte antibody positivity of blood donors show a similar relation with TRALI.

INTRODUCTION: The fraction of transfusion-related acute lung injury (TRALI) cases preventable by deferral of allo-exposed donors has previously been estimated, under the assumption this indirectly estimated the contribution of leucocyte antibodies to the occurrence of TRALI. Our aim was to estimate the fraction preventable by deferral of leucocyte antibody positive donors and to investigate the validity of allo-exposure as a marker for leucocyte antibodies. METHODS: All donors involved in a series of previously published TRALI patients were tested for leucocyte antibodies. The observed number of antibody positive donors was compared to the expected number. From this comparison we estimated the contribution of leucocyte antibodies to the occurrence of TRALI and compared this to the previously reported estimate for allo-exposed donors. RESULTS: Sixty-one TRALI patients were included. Of 288 involved donors 43 were expected and 67 were observed to be leucocyte antibody positive. The observed percentage of positive donors was 8.3% (95% confidence interval (CI): 5.1-11.5%) in excess of the expected. Overall 59% (95% CI: 34-85%) of TRALI cases was estimated to be preventable by the exclusion of all leucocyte antibody positive donors. For plasma-poor products this was 16% (95% CI: -5.0 to 36%). CONCLUSIONS: These estimates were similar to those previously published for allo-exposed donors. This suggests allo-exposure status can effectively be used in donor deferral strategies.

[Transfusion-related acute lung injury (TRALI) in the Netherlands in 2002-2005]. / Transfusiegerelateerde acute longbeschadiging (TRALI) in Nederland in 2002-2005.

OBJECTIVE: To determine the number of reported cases of transfusion-related acute lung injury (TRALI) in the Netherlands in 2002-2005 and to determine how many cases were associated with incompatibility between leukocyte-reactive antibodies in the donor plasma and leukocytes or antigens in the recipient. DESIGN: Retrospective national case review. METHOD: Cases of TRALI reported in 2002-2005 were assessed according to the national clinical definition of TRALI, and the relationship between TRALI and transfusion was assessed. Additional clinical details were requested from the treating hospital as necessary. The results of leukocyte serological tests from donors and recipients were linked to clinical cases. For cases with positive leukocyte serological tests, the relevant blood components and the sex of the donor were recorded. RESULTS: Of the 46 cases reported, 6 had insufficient information. 8 cases did not meet the definition or had another more likely diagnosis. There was a trend toward an increase in the number of reports: 12 cases were reported in 2005, corresponding with 1:60,000 blood components. Of the 40 evaluable cases, 32 (80%) met the definition of TRALI and were deemed to be definitely (n = 16), probably (n = 5) or possibly (n = 11) related to transfusion. Severity ranged from moderate to life-threatening, and there was one TRALI-related death. Leukocyte serology was fully investigated in 18 cases: 13 (72%) had leukocyte incompatibility and in 5 cases exclusively fresh frozen plasma from a female donor was implicated.

[Transfusion reactions in patients: haemovigilance reports to the Dutch National Haemovigilance Office in 2003]. / Transfusiereacties bij patiënten: hemovigilantiemeldingen aan het Landelijk Hemovigilantiebureau over 2003.

OBJECTIVE: National registration and analysis of unexpected side effects and incidents associated with blood transfusion (together termed 'transfusion reactions') in 2003 in order to arrive at recommendations to improve safety in the transfusion chain. DESIGN: Observational METHOD: A uniform national reporting form with definitions and a reporting manual were sent to all Dutch hospitals in the spring of 2003 with the request to report transfusion reactions retroactively to January 2003 to the Dutch National Haemovigilance Office 'Transfusion reactions in patients' (TRIP). TRIP is an independent organisation managed by representatives of professional societies that are involved in blood transfusion. Each hospital was given a reporting code. The reports were in principle voluntary and anonymous with regard to both the patient and the attending physician. Transfusion reactions were assessed for severity as well as for the level of probability with which they could be ascribed to the transfusion. RESULTS: Reports were received from 82 (80%) of the hospitals; 9 hospitals informed the TRIP explicitly that there had been no transfusion reactions in 2003. A total of 267 reports were received. Of these, 803 (63%) were graded for severity and of these 803, 52 (6%) were grade 2 ('moderate to severe morbidity') or worse. In the categories involving possible infectious complications, there were 2 reports of bacterial contamination that were judged, on review, to be due 'with certainty' to the transfusion. 34 reports concerned transfusion of the wrong blood product, resulting in a total of 9 transfusion reactions (4 of grade 2). The total number of reports concerning 2003 was 1.6/1000 blood products. CONCLUSION: The participation by the hospitals was high in the first year of national reporting, 2003. Most of the reports were of non-serious reactions known to be possible side effects of blood transfusion; 52 reports were rated as grade 2 or worse.

[International databases: usefulness and limitations in hemovigilance]. / Les bases de données internationales en hémovigilance.

A number of international databases are well-known and useful tools for professionals in blood transfusion. The advent of national hemovigilance registries and an international focus on transfusion practice and transfusion safety has led individuals and organisations to collect and compare data. This has led to the development of internationally useful indicators, for instance figures for the numbers of red cell products transfused per 1000 in the population. An international database of hemovigilance data (surveillance database for transfusion associated adverse reactions and events [STARE]) is currently being developed by the International Hemovigilance Network. In the pilot phase, it is seen that differences exist between the rates of adverse reactions and events. Factors such as the working method and definitions in use in the countries must be taken into account and efforts made to increase uniformity of the data. The remaining variability might then generate hypotheses of areas or types of increased risk, which would need to be further investigated in specific projects.