Adverse reactions following transfusion of blood components, with a focus on some rare reactions: Reports to the International Haemovigilance Network Database (ISTARE) in 2012-2016.

OBJECTIVES: The International Haemovigilance Network's (IHN) ISTARE database collects surveillance data on all adverse reactions (AR) associated with transfusion of blood and blood components, facilitating the sharing of best practice and benchmarking for improving blood safety and quality. Up to 2012, no publications discussed certain rare AR. The aim of this study is to examine ISTARE data on AR from 2012 to 2016, focusing on hypotensive reactions, post-transfusion purpura (PTP), transfusion-associated graft versus host disease (TA-GvHD), hyperkalemia and hypocalcemia. MATERIALS AND METHODS: National Haemovigilance Systems (HVS), provided aggregate annual data on AR by type of reaction, severity, imputability to transfusion, and blood component implicated. Twenty-nine HVS provided 104 annual reports covering 107,778,290 blood units issued. RESULTS: Among AR reported, 25% were serious, including 368 deaths. The 284 transfusion-transmitted infections included 187 bacterial infections, 84 viral and 13 parasitic or fungal; nine deaths resulted. AR related to the respiratory system transfusion-associated circulatory overload, transfusion-related acute lung injury and transfusion-associated dyspnoea accounted for 8.3% of all AR, 20.1% of serious, and 52.2% of deaths. Of 1634 rare AR, 1565 were hypotensive, 38 PTP, 17 GvHD, 9 hyperkalemia and 5 hypercalcemia. Half were serious and 16 fatalities were recorded (13 hypotensive, 2 GvHD, one PTP). Among 14 countries that reported any hypotensive AR, incidences diverged widely. CONCLUSIONS: ARs in this group are frequently severe or life-threatening. Hypotensive AR are the most common, but may have been overlooked and counted under allergic and other AR presenting with hypotension. Compliance with the ISBT definition may be suboptimal, thus its real incidence may be higher. Data on GvHD may contribute to clarifying the role of leukodepletion with or without irradiation. ISTARE continues to be a useful surveillance tool for all transfusion AR and provides relevant insights into overlooked and rare AR, thus offering important contributions towards maximising transfusion safety.

[Postdonation information: the French fourth hemovigilance sub-process]. / L'information post-don, le quatrième sous-processus de l'hémovigilance.

Postdonation information is the knowledge of information about the donor or his donation, occurring after it, which challenges quality or safety of the blood products stemming from this or other donations. Classical hemovigilance sub-processes concerning donors or recipients adverse events do not cover this topic. France is just about to make it official as a fourth sub-process. Less formal management of postdonation information is already set up for more than ten years. French data of the year 2013 are presented, including the regional notification level and the national reporting one. A significant level of heterogeneity is observed as for other hemovigilance sub-processes. It is mainly due to subjective rather than objective differences in risk appreciation. A real consensual work is expected about it in the future.

[The blood donors' haemovigilance in France]. / L'hémovigilance des donneurs de sang en France.

This work aim to present the descriptive analysis of serious adverse reactions in donors (dSAR's), which were notified in 2010 and 2011 in the French national haemovigilance database "e-FIT" (Internet secured haemovigilance reporting system). Some data, which are necessary for this analysis, also come from the regional haemovigilance coordinators' reports (RHC). The other parts of haemovigilance in the context of donation, without donors adverse reactions, such as post-donation information (PDI), adverse events occurred in the blood collection steps of the transfusion chain and epidemiology are not subject to this work analysis. This work shows that the quality of the data gradually improved since the setting up of the notification system of dSAR's. These data are particularly rich in learning lessons, but are still improving. It allows us to confirm that donor's safety, blood components quality, while preserving the blood components self-sufficiency in France, remains a priority. For these reasons, it is important to continue this haemovigilance awareness and to implement necessary actions that would be required for the protection of the donor's health and comfort during donation.

[Errors of red cell concentrates recipients: method of analysis using the adverse events notified to the hemovigilance network in 2009]. / Erreurs de destinataire de concentrés de globules rouges : méthode d'analyse à partir de déclarations d'incidents de la chaîne transfusionnelle en 2009.

CONTEXT: Among the adverse events in the blood transfusion process, transfusion to a "wrong" patient is potentially dangerous, as it can lead to an adverse reaction at least in case of ABO incompatible red cell concentrate. MATERIAL AND METHODS: The "Root Cause Analysis" working party of the National Hemovigilance Commission developed a tool to collect this type of adverse event, and tested it on a sample of 43 cases involving red cell concentrates notified between March, 2009 and February, 2010. RESULTS: One hundred and nine failures of a step in the transfusion process were observed, i.e. 2.5 failures per adverse event. Failures may occur early in the process. However, they are mainly found at the time of issuing of the blood component, and further, in the clinical ward. How the failure is eventually detected is not always described when the blood component has been fully transfused, in contrast with the cases where actual transfusion to the wrong patient has been prevented. Knowing the way of failure detection enables an objective approach of the efficacy of the numerous existing safety measures. In this sample, bedside controls (documents check as well as the use of anti-A and anti-B reagents with patient's blood and red cell concentrates) detected the failure in three cases out of 34, which were not detected before, showing an efficacy similar to the administrative control done at reception in the clinical ward. CONCLUSION: The document, set up to analyse step by step these cases of patient errors, will be used in the future to analyse all similar cases, not only with red cell concentrates, but also with platelet concentrates and fresh frozen plasma, ultimately in order to improve their prevention.

[Factsheets: support in the analysis of recipients' adverse reactions]. / Fiches techniques: aide à l'analyse des effets indésirables receveurs.

In order to help the analysis of adverse effects of transfusion, factsheets have been written by working groups of the French agency for the safety of health products ANSM. Each factsheet deals with a blood transfusion side effect and is composed of five parts, including pathophysiological mechanisms, diagnostic criteria, management recommendations, etiologic investigations and rules for filing the notification form to ANSM. Since 2006, 11 factsheets have been published on the French haemovigilance network website. The major characteristics of the two last sheets published "post-transfusion purpura" and "non erythrocyte incompatibility reaction" are presented, followed by the updated card for "allergy". These factsheets give relevant guidelines allowing better evaluation of recipients' adverse reactions, particularly their diagnosis, severity and accountability. They also could initiate studies among European and international haemovigilance networks.

[Seventeen years of haemovigilance in France: assessment and outlook]. / Dix-sept ans d'hémovigilance en France: bilan, perspectives.

Since 1994, the French haemovigilance network has not stopped evolving. Based initially on the reporting of informations and incidents related to recipients, it quickly became interested in the procedures and other activities related to blood component transfusion, in order to improve blood safety. Despite some failures (under reporting, heavy declarative management), the French haemovigilance network is going to continue working on improving blood safety, both at the level of the recipients and the donors, and participate to the global improvement of quality of care.

[European regulation on blood and blood components]. / Réglementation Européenne relative au sang et à ses composants: déclinaison au niveau de la réglementation Française.

The European regulation on blood and blood components is declined in four directives: the Directive 2002/98/EC known as "mother Directive" and three directives called "daughter Directives" 2004/33/EC, 2005/61/EC and 2005/62/EC. It constitutes a common basis of provisions of quality and safety of blood in the European Union (EU), thus guaranteeing this safety and this quality with the whole of the citizens circulating in Member States of the Union. It cannot prevent a Member State for maintaining or introducing more stringent protective measures. It encourages the anonymous, voluntary and unpaid blood donations. It envisages many provisions for the prospective blood donor eligibility, the blood collection, the testing, processing, storage, transport, distribution and issuing of blood and blood components and the haemovigilance. In the field of the haemovigilance, this European regulation widened the field of competence of the national systems to the notification of serious adverse events of the transfusion chain and the serious adverse reactions, which have occurred in the blood donors. The European directives were transposed in the French national law between 2004 and 2007 by legislative and lawful ways.

[Patient safety and root cause analysis]. / Sécurité des patients et analyse des causes racines.

Safety in the field of transfusion medicine has greatly improved in France. The risk of viral transmission has decreased by a factor greater than 1500 within the last 20 years. In comparison, the risk related to ABO error has decreased only by half. The reporting of critical incidents, which occur at any step of the transfusion procedure is now mandatory in France and is subject to an in-depth analysis, using methods close to that used in aviation safety. The goal of these analyses is to better understand human factors in order to implement more adequate prevention measures.

Use of random versus apheresis platelet concentrates.

The respective use of random (RPC) and apheresis (APC) platelet concentrates is highly heterogeneous among countries, ranging from 10 to 98% RPC in countries supposed to provide a similar transfusion service to patients. Moreover, when considering each country in the past 10 years, one can observe that some have changed their policy, switching from a majority of APC to RPC or vice versa. This presentation intends to analyse which factors may impact such decisions. For many years, the only available platelet component was a RPC obtained from whole blood donation by a two centrifugation steps process, the "platelet rich plasma" or PRP method. Since the beginning of the 1970s, APCs became available, with in fact many different techniques leading to many APCs that may not be equivalent. Since the end of the 1980s, a new method of RPC preparation was developed, using the buffy-coat (BC-PC), providing a blood component with highly preserved platelet functions as compared to RPCs prepared by the PRP technique. Finally, the use of each of these components either native, or leuco-reduced, or suspended in a storage solution, or processed with a pathogen inactivation technique adds new layers of complexity to compare them. Innumerable references can be found in the literature describing in vitro functional parameters of platelet concentrates. Although it is clear that BC-RPC retain much more their in vitro functions than PRP-RPC, indicating that no one should use the latter any more, it is much more difficult to distinguish differences between other PCs. Conversely, only a very few studies have been published related to a comparison of clinical efficacy of RPC versus APC, the endpoints being mainly CCI. Similarly to the in vitro studies, although RPC prepared with the PRP method show the lowest CCIs, no clear difference exists between "modern" RPC and APC. Another factor that may impact policy decision is the occurrence of adverse reactions in recipients. When considering only comparable data, for example leuco-reduced RPC versus leuco-reduced APC, there is now evidence that the latter is more associated with adverse reactions in recipients: data from hemovigilance in France show that, although no difference is noted for febrile non haemolytic transfusion reactions, nor for bacteria contamination, the incidence of allergic adverse reactions is about four times higher with APC as compared with RPC. Other aspects may impact the decision: the fact that using APC in place of RPC reduces the total donor exposure of patients was considered critical in some countries to reduce the risk of transmission of blood transmissible disease. Finally, the cost of the components, much higher for APC may be considered.