Haemovigilance Annual report 2012

Transcription

1 Haemovigilance Annual report 2012 Autumn 2013

2

3 1 Annual Haemovigilance Report 2012 The Annual Report was written by: Dr. Morven Rüesch and Dr. Markus Jutzi Clinical Reviewers Haemovigilance / Swissmedic morven.rueesch@swissmedic.ch markus.jutzi@swissmedic.ch Additional information is available under «Haemovigilance» on the Swissmedic website:

4 2 Table of Contents Introduction / Additional information 3 1. General information on haemovigilance Definition of haemovigilance Summary 5 2. Reports received In general Distribution of reports Transfusion reactions Frequency Imputability (relationship to transfusion) Severity Transfusion reactions by blood component Number of transfused blood components and 8 risks in Switzerland Numbers of transfusions Reporting rates Transfusion risks Risks of life-threatening and fatal transfusion reactions Special aspects regarding platelet concentrates Risk-reduction measures Transfusion-transmitted infection (bacterial contamination of labile blood products, transmission of viral infections by blood components) Reports of transfusion-transmitted infection Results of lookback studies performed by NRC IBCT (transfusion errors / incorrect transfusions) and near miss events IBCT Near miss events Sample case reports Deaths Transfusion reactions of grade 3 severity Other transfusion reactions Cases of IBCT Near miss events Abbreviations Bibliography 28

5 3 Introduction In this Annual Haemovigilance Report we aim to provide a descriptive and interpretive snapshot of the most important current data and findings on haemovigilance in Switzerland and in this way to provide a clear picture of the present safety profile of blood transfusion in the country. In the case of avoidable events we describe the risk reduction measures that have already been taken and the effects that these measures have had to date. In addition, we refer to planned future developments aimed at improving transfusion safety. The data presented are thus selective and background information is generally referred to only in brief. For a more detailed description including definitions and a more detailed analysis of individual topics, we would refer the reader to our website. Additional information on haemovigilance and transfusion medicine Comprehensive information about haemovigilance at Swissmedic is available at: haemo.asp Recommended investigations for suspected transfusion reactions (TRs) and criteria for assessing events, the severity of these, and causal relationships are given in the document «Klassierung und Abklärung von Transfusionsreaktionen» (currently available in German, French and Italian). These criteria correspond to the definitions established by the ISBT Haemovigilance Working Party. Background information and more detailed analyses of individual aspects are to be found under «Publikationen» («Publications»). Haemovigilance annual reports Information and fact sheets Scientific publications Presentations Works presented at haemovigilance conferences and workshops (by Swissmedic itself and, where made available, by guest speakers) are available at: Works presented at the «Swisstransfusion» annual conference since 2011 are available at: Guidelines / recommendations / directives: Links to international haemovigilance bodies: As aids to the reporting of the most common reportable events and information, we supply the following forms: Reporting of transfusion reactions Reporting of near misses/ibct Reporting of change of haemovigilance officer Reporting of number of blood components transfused per year

6 4 1. General information on haemovigilance 1.1. Definition of haemovigilance The International Haemovigilance Network (IHN) defines haemovigilance as follows: «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» ( The concept of a transfusion chain is central to this definition. The diagram below shows which occupational groups play a role in the chain and what actions have to be performed in what order so as to ensure a successful transfusion. To this end the quality assurance system for the use of labile blood products must regulate the interfaces between the involved institutions and the entire process within the transfusing institution in order to ensure that the right blood product is administered to the right patient in the right way at the right time. Figure 1

7 5 1.2 Summary In 2011 the Haemovigilance Working Party of the International Society of Blood Transfusion (ISBT) revised the diagram that had been used until then to classify adverse transfusion events (see Haemovigilance Annual Report 2008, page 7). In the revised diagram near miss (NM) events are classified as a separate group, since in their case unlike in TRs and incidents by definition no transfusion has been given. Figure 2 with evidence of a febrile non-haemolytic transfusion reaction (FNHTR)). On this basis a total of adverse events were reported as having occurred in temporal association with a transfusion. Table 1: Number of haemovigilance reports 2012 Category Number Number of reports of adverse transfusion events Number of events after transfusion Number of IBCT reports 57 Number of near miss reports 619 Total number of reports A closer analysis of these reports revealed that 13 cases were in fact not TRs, but events due to other causes. Exclusion of these events reduces the total number of TRs reported in 2012 to Distribution of reports Figure 3 Number of events 2012 by type As the investigation, assessment and reporting of TRs are focused mostly on the biological aspects of the event, most of the fields in the reporting form for TRs are for clinical information. In cases of IBCT (incorrect blood component transfused) the origins of the event are also of interest. Analysis of these is facilitated by the structure of the NM/IBCT reporting form. In the case of transfusion errors/ibct in which there is a clinical suspicion of a TR, information on both these aspects is required for a complete analysis NM IBCT TR 2. Reports received 2.1. In general In 2012 Swissmedic received a total of 1676 haemovigilance reports. Of these, were classified as TRs, 57 as transfusion errors/ibct, and 619 as near miss (NM) events. Twenty-three reports were classified as «double events» on the basis that the clinical features indicated a high likelihood of two different TRs (e.g. evidence of a mild allergic reaction simultaneously Given that the number of TRs reported in 2012 was 5% less than in the previous year, the increase in the total number of reports received in 2012 is due to a 33% increase in NM events and a 52% increase in IB- CTs. From this we infer an increased level of interest in process deviations and in the conclusions that can be drawn from an analysis of these.

8 6 2.3 Transfusion reactions (TR) As in previous years, the most common types of TR were FNHTR, alloimmunisation, and allergic TR. These three categories account for approximately 90% of the reported TRs Frequency Still in fourth and fifth place in terms of frequency were reports of transfusion-associated circulatory overload (TACO) and of hypotensive TR. The proportion of TRs accounted for by TACO fell by a third (5.6% to 3.9%) compared to the previous year, whereas the proportion accounted for by hypotensive TRs remained almost unchanged (2.3% vs. 2.2% in the previous year). Similarly, the proportion of suspected TRs accounted for by the rest of the categories remained unchanged from the previous year. Figure 4 2.3% TR 2012 by classification and frequency 1.0% 0.5% 0.5% 0.1% 2.2% 0.2% 0.1% 3.9% 18.1% 27.7% 43.5% FNHTR Allo-immunisation Allergic TR TACO Hypotensive TR Other Haemolytic TR Infection TAD Hyperkalaemia Imputability (relationship to transfusion) The term «imputability» refers to the estimated likelihood of a causal relationship between the transfusion and the observed event. In 2012 a total of 599 events (59.3% of reported TRs) were considered to be probably or certainly attributable to a transfusion. Table 2: Number of events 2012 by category and imputability Imputability All Low imputability Imputability «possible» High imputability Allergic TR (79.7%) FNHTR (29.4%) Alloimmunisation (99.6%) HTR: acute delayed Hyperkalaemia Hypotensive TR Infection, viral bacterial TACO (61.5%) TAD TRALI Other PTP Number of events 1, (7.1%) 339 (33.6%) 599 (59.3%) This year we decided to list reports in which imputability was assessed as «possible» separately. This shows more clearly how few of the reported cases (only 7%) were considered to be probably not attributable to transfusion (imputability «unlikely» or «excluded»). This in turn attests to reliable detection and reporting of possible TRs.

9 7 The imputability category «possible» is assigned to cases in which the observed reaction may have resulted either from the transfusion or from other clinical factors. Most of the events in this category were FN- HTRs. Fever is the most common clinical feature that must be regarded as possible evidence of an (incipient) TR when it occurs in temporal association with a transfusion. On the other hand, it is a nonspecific sign and FNHTR is therefore a diagnosis of exclusion. Only in 29% of cases was the transfusion considered to be the most likely cause of the febrile reaction, whereas in 58% of cases it was felt that other causes may have led to the fever (pre-existing febrile state, non-transfusion-associated infection, underlying disease, etc.). The high proportion of reports of allergic TR and of alloimmunisation in which imputability was considered to be high shows that most such events are correctly identified and documented at an early stage. Though the signs and symptoms of circulatory overload are not always unequivocal, this provisional diagnosis was confirmed in two-thirds of cases. Overall, these figures underline how important it is that the first signs of a possible TR be detected in reliable fashion and that the first necessary measures be taken promptly. In order to prevent the occurrence of potentially life-threatening developments while it is still possible to do so, any nonspecific change in the patient s general condition such as fever or dyspnoea or changes in the patient s vital parameters or subjective state that occur during a transfusion must be regarded as an indication for immediate suspension of the transfusion, an initial assessment of the overall situation, and where necessary, further investigations. An assessment must be made as to whether the event has the potential to become life-threatening (especially in the case of transfusion error, TACO, allergic TR, and TRALI). If the answer to this question is «yes», the transfusion should not be resumed, further investigations should be undertaken, and symptomatic treatment should be given on the basis of the clinical assessment. Where an analysis of the signs and symptoms, the overall situation, and the course of the event permit the conclusion that no dramatic developments are to be expected and that the reaction is likely to be adequately controlled by the measures already taken, consideration can be given to resuming the transfusion with appropriate monitoring of the patient Severity Table 3: High imputability events 2012 by category and severity Severity All Grade 1 Grade 2 Grade 3 Grade 4 Allergic TR mild anaphylactoid anaphylactic 4 4 FNHTR Alloimmunisation HTR: acute delayed 1 1 Hypotensive TR TACO TAD 2 2 TRALI 1 1 Other 5 5 PTP 1 1 Number of events Percentage of all events 100% 47.4% 49.7 % 2.7% 0.2% The proportions of events with the various grades of severity differ slightly from those of the previous year. In 2012 the proportion of reported TRs assessed as non-severe (Grade 1) was 47% (previous year: 51%), while the proportion assessed as severe or having caused permanent damage (Grade 2) was 50% (previously: 45%). In 2012 the proportion of TRs assessed as life-threatening or fatal was slightly less (2.9 %, 17 out of 599 TRs) than in the previous year (4%, 23 out of 613 TRs). In the case of packed red blood cell (prbc) transfusions the number of Grade 3 reactions reported in 2012 (9) was one less than in 2011; in the case of fresh frozen plasma (FFP) transfusions this number was unchanged (three cases in 2011 and also in 2012); in the case of transfusions of multiple blood components this number fell from five to one grade 3 TR and in the case of platelet concentrate (PC) from five to three cases. The one fatal case in 2012 was associated with prbc transfusion.

10 8 In 2012 there were 10 reports of deaths occurring in temporal association with a transfusion. The final assessment identified one case in which there was a high probability of a causal relationship between the TR and the death of the patient. In the remaining cases either a cause of death unrelated to the transfusion was found or else a causal relationship could be neither confirmed nor excluded. Figure 5 35 Grade 3&4 TRs As is generally the case, alloimmunisation (267), FN- HTR (103), allergic reaction (44), and circulatory overload (23) accounted for the majority (73%) of TRs reported after prbc transfusion. Apart from one febrile reaction, only allergic reactions (24 after FFPq, six after FFP-SD) were observed in association with transfusion of plasma. Similarly, allergic reaction (65) was the most commonly reported reaction after PC transfusion, in this case followed by FNHTR (22), alloimmunisation (8), isolated cases of delayed HTR, TACO, and TRALI, and one reaction (pain) that fell into the «Other» category. As in the previous year, no TR due to bacterial contamination of PC was reported. Transfusion of multiple blood components led to six allergic reactions, three FNHTRs, four cases of alloimmunisation, one hypotensive TR, one TACO, and one TR categorised as «Other» (passive transmission of HBV antibodies) Other Hyperkalaemia Delayed HTR TAD Hypotensive TR Bacterial infection TRALI Acute HTR TACO Allergic TR 2.4 Number of transfused blood components and risks in Switzerland Numbers of transfusions The annual statistics of the Blood Transfusion Service of the Swiss Red Cross (BTS SRC) show the number of blood components issued in Switzerland. The table below shows the figures for the past five years. As before, the most common life-threatening events were allergic TR and circulatory overload Transfusion reactions by blood component The percentage distribution of the 599 high-imputability TRs by blood component was the same as in Table 4 prbc (packed red blood cells) 75% (451) FFPq 4% (25) FFP-SD PCa (apheresisderived) PCb (whole blood-derived, buffy-coat) 1% (6) Multiple blood components 16% (94) 1% (6) 3% (16) Table 5: Numbers of transfusions Blood components prbc FFP (therapeutic units) PC (products) Total blood components Once again, the total number of blood components issued was less than in the preceding year, approximately 3% fewer prbc having been issued than in And once again, use of PC increased, in this case by 3.5%. In parallel with the introduction of the Intercept procedure the proportion of PC derived from whole blood rose from 14% in 2010 to 23% in 2011 and 34% in Even with exclusive use of pathogen-inactivated PC there is no evidence of any overall increase in the demand for blood components.

11 Reporting rates The overall reporting rate rose again in 2012 and is now 4.4 reports (including NMs) per thousand transfusions. Figure 6 Reports per 1,000 transfusions Progression of the reporting rate The increase in the overall reporting rate and in the number of reported NM events and transfusion errors contrasts with a slight decrease in the number of TRs as compared to the preceding year Quantification of transfusion risks provides the treating doctor with a basis for undertaking a risk-benefit analysis when considering transfusion and for providing advice to the patient about possible adverse effects. The frequency figures shown here provide information on the type and magnitude of transfusion risks in Switzerland at the present time. Both the unavoidable and the potentially avoidable risks of transfusion are shown. In the case of potentially avoidable transfusion risks the frequency of events suggests where risk-minimisation measures are indicated and documents the effect of measures already taken. Based on the number of TRs with high imputability and on the blood components issued, we express the risks of TRs 2012 for prbc, plasma, and PC in the format «one event per XXX issued products», limiting our consideration to TRs with more than 10 reports (Figures 7 and 8). Because of their small absolute numbers of cases, hypotensive (6) and haemolytic (4) TRs, TAD (2), and events categorised as «Other» (3) occurring in association with prbc and plasma transfusions cannot be expressed reliably as risks. In the case of PC in addition to the risks indicated in Figure 8 one case each of acute haemolytic TR, TACO, TRA- LI, PTP, and «Other» was reported. Figure 7 Risks of TR for RBC and Plasma 2012 Total Risk RBC Allo-immunsation RBC Total Risk FFP Allergic TR FFP FNHTR RBC Allergic TR RBC ~ 1:7'000 ~ 1:3'000 ~ 1:1'700 ~ 1:1'600 ~ 1:1'100 ~ 1: Transfusion risks TACO RBC ~ 1:14'000 Figure 8 Risks for Platelet transfusions 2012 Risk all events Allergic TR ~ 1:500 FNHTR ~ 1:1'500 Allo-immunisation ~ 1:4'000 ~ 1:350

12 Risks of life-threatening and fatal transfusion reactions Figure 9 shows the categories and numbers of Grade 3 and 4 TRs to all blood components that have occurred over the past five years. The numbers of cases are small and show a diminishing trend over the past two years. As the risks cannot be precisely quantified for an individual year, we estimated the risks from the cumulative data Because the number of cases is diminishing, it may be assumed that the current risks for Grade 3 and 4 TRs are not higher than those indicated in Figure 9. Figure 9 Risk all events Allergic TR Acute HTR Hypotensive TR Bacterial infection Hyperkalaemia Delayed HTR TRs Grade 3 & , all blood components TACO TAD TRALI 5 / ~ 1:400'000 5 / ~ 1:400'000 1 / ~ 1:2 Mio 1 / ~ 1:2 Mio 25 / ~ 1:80'000 7 / ~ 1:300'000 6 / ~ 1:300'000 6 / ~ 1:300' / ~ 1:30' / ~ 1:15'000 Total Over this period three transfusion-associated deaths (in 2008 one TACO after FFP and one TRALI after PC; in 2012 one TACO after prbc) occurred Special aspects regarding platelet concentrates Following the introduction in 2011 of pathogen inactivation of PC, the data from the past four years make it possible to compare the transfusion risks of conventional platelet concentrate (cpc) with those of pathogen-inactivated platelet concentrate (PI-PC). A background report on this was published in the Swiss Medical Forum in March 2013 (1). An updated assessment of PC transfusion risks was presented in the form of a poster at the International Haemovigilance Seminar 2013 (2). In summary, it was found that as well as reliably preventing septic TRs, introduction of the Intercept procedure for all PCs led to a reduction in the number and severity of non-infection-related TRs after PC transfusion. Table 6 Transfusion reactions Units transfused cpc PI-PC Risk * Reports Risk* Reports Risk* All high imputability reports High imputability reports Grade 3 & 4 *Risk = 1 reaction per x PC 223 ~ 1: ~ 1: ~ 1: ~ 1: In relation to the information given in the two publications referred to above it should now be noted that the estimate of the number of PI-PC to be issued in proved to be too high by about products. During the period of observation a total of cpc and (instead of an estimated ) PI-PC were in fact transfused (2009: : 2010: ; 2011: CPC and PI-PC; 2012: PI-PC). This did not alter the magnitude of the calculated risks Risk-reduction measures With regard to TRs a distinction must be made between events that are potentially avoidable and those whose frequency of occurrence cannot be significantly influenced by presently available measures. FNHTRs, allergic and hypotensive TRs, TAD, and PTP cannot be reliably avoided. In the case of these events attention must instead be focused on detection and treatment of the clinical signs and symptoms. Transfusion-associated hyperkalaemia and formation of alloantibodies can be avoided to some extent by choosing the most appropriate blood products. Potassium load is less with prbc that have been stored for as short a time as possible and with irradiated products when the interval between irradiation and transfusion is kept to a minimum. Potassium filters have yet to be accepted for use in clinical practice and there is insufficient evidence that they are effective. In order to prevent alloimmunisation in vulnerable patients (e.g. girls and women of pre-childbearing or childbearing age, patients with a long-term transfusion requirement), every effort should be made to achieve the closest possible match between the antigen profile of the blood product and that of the patient (Rh/K phenotype compatible, documented compatibility with other blood group antigens) (3).

13 11 Though these measures cannot completely prevent the formation of alloantibodies, they largely prevent clinically relevant alloimmunisation. Table 7 lists potentially avoidable risks and their present magnitude. TACO 1: transfusions 1) IBCT Transfusion errors (ABO) Transfusion errors (ABO) 1:7 000 transfusions 1) 1: transfusions 1) 1:7 000 transfusions 1) Haemolytic TR 1: transfusions 1) TRALI 1: ( ) 2) 1: ( ) 3) Bacterial infection 1: ) HBV 1: blood donations 5) HIV 1:4 000,000 blood donations 5) HCV 1: blood donations 5) TaGvHD ~ 1: ) 1) Swiss haemovigilance data ) Swiss haemovigilance data ) Swiss haemovigilance data ) Swiss haemovigilance data ) Berne Blood Transfusion Service, training event held on 29/11/2011 (4) 6) Swiss haemovigilance data The figures for TACO, IBCT/transfusion errors, and haemolytic transfusion reactions (HTRs) are based on the reports received in For events with a small number of cases per calendar year, cumulative data from a number of years were used. For all events, frequency was calculated in relation to the number of products issued in the period concerned. In the case of TRALI the figures for the period before and the period after the introduction of the male-donor- plasma-only strategy are given ( and , respectively). The figure for the frequency of bacterial infections for all blood products is based on data obtained since the introduction of pathogen inactivation of PC. The figures for viral infections were provided by the national reference centre for infections transmissible by transfusion (NRC). Various product-specific measures such as donor selection, screening for infection markers, skin disinfection, use of the «pre-donation sampling pouch», leukodepletion, irradiation, and pathogen inactivation procedures have reduced the risk of transfusion-associated infection, TRALI, and TaGvHD to significantly less than one per blood components issued. In contrast to these product-specific risks, the causes of circulatory overload (TACO), transfusion errors (IBCT), and haemolytic TRs are to be found in procedural errors in the transfusion process. Factors that predispose patients to reduced volume tolerance during transfusion include age (children, age >60 years), pre-existing heart disease, chronic (severe) anaemia, renal failure, hypoalbuminaemia, and pre-existing positive fluid balance. These factors must therefore be actively looked for in all patients who are to undergo transfusion and use of an appropriate combination of the following recommended preventive measures must be stipulated in the prescription for transfusion:» Check indication for transfusion.» Document fluid balance before transfusion.» Prescribe a transfusion rate of 1 ml/kg bodyweight/ hour.» Monitor patient closely (BP, respiration, pulse oximetry if required).» Administer prophylactic diuretics if required. All the above must be stipulated in the standard operating procedures for transfusion. Cases of IBCT, transfusion errors in the narrow sense, and haemolytic TRs that result from these are likewise not due primarily to product characteristics. Rather, they generally result from a sequence of several incorrect actions at various sites of the transfusion chain. The most common deviations from correct procedure are mixing up of samples or patients due to incorrect checking of patient identity either when obtaining blood for pre-transfusion testing or immediately prior to transfusion. Errors that occur at other sites in the transfusion chain (e.g. issue of a product to the wrong patient) can likewise be detected at the final check immediately before the transfusion is started provided that the patient s blood group, surname, given names, and date of birth are correctly checked against the data indicated on the blood product to be transfused and on the blood group card. This check is thus the last opportunity to avert an impending transfusion error. Increasing use is being made of aids to improvement of patient ID such as ID wristbands and radio frequency identification (RFID).

14 Transfusion-transmitted infection (bacterial contamination of labile blood products, transmission of viral infections by blood components) Reports of transfusion-transmitted infection No cases of transfusion-transmitted bacterial infection were registered in No cases of transfusiontransmitted viral infection were reported in Results of lookback studies performed by NRC No cases of transfusion-transmitted viral infection were announced in Switzerland in A total of nine donor lookback (DLB) and three patient lookback (PLB) studies on viral infections were instigated. One of these was on HIV, seven were on HBV, and four were on HCV infection. Still ongoing are four DLB studies on HBV and one on HCV infection and two PLB studies on HBV infection. In the other cases transfusion-transmitted infection was excluded. 2.6 IBCT (transfusion errors / incorrect transfusions) and near miss events The number of reported IBCTs increased from 38 in 2011 to 57 in 2012 and accounted for 3.4% of all reports in 2012 (cf. 2.5% in 2011). The number of reported near miss events increased even more, to 619, and accounted for 37% of all reports in 2012 (cf. 30% in 2011) IBCT The term «incorrect blood component transfused» (IBCT) refers to transfusion of a blood product that was intended for another patient or was not optimally suited to the patient to whom it was administered. Of the 57 IBCTs reported, four occurred at the «Preparation» stage of the transfusion chain, 27 at the «Laboratory» stage, 21 at the «Administration» stage, and five were classified as «Other». Table 8 Stage of transfusion chain Number Examples Preparation 4 Prescription/ordering Laboratory 27 Administration Other 5 Issue (18) Testing (8) Administration (1) 21 Transfusion Wrong product prescribed, specification not stated in order including 6 cases of failure to take account of pre-existing alloantibodies that were no longer detectable 2 cases of mixing up of samples resulting in the wrong blood group being determined, 1 case with acute HTR 2 sets of case notes for one patient including 7 cases of patient mix-up, 1 case of ABO incompatibility with acute HTR

15 13 The main focus in the analysis of IBCTs is on transfusion errors. The term «transfusion error» refers to the transfusion (other than in emergency situations) of a product whose compatibility in terms of AB0, Rh, or other blood group antigens is not assured. This includes transfusion of a blood product that was intended for another patient. These deviations can lead to serious and even fatal transfusion reactions and are as a rule preventable. The following description is limited to the 25 reported events that fall into this category. Table 9 Transfusion error AB0 system, incompatible AB0 system, fortuitously compatible Antibody-incompatible Administration of untested prbc Number Description 7 5 with no TR (3x FFP, 2x prbc: wrong BG after HSCT) 2x prbc-transfusion with acute HTR 7 6x prbc, 1x PC 9 1x with possible delayed HTR, 4x with boosting of a preexisting antibody 2 not an emergency situation Analysis of the sequence of events leading up to the 14 transfusion errors related to the ABO system revealed the following basic deviations: In the three cases of AB0-incompatible FFP transfusion the required specification was either not adhered to or not known and products of the wrong blood group were issued: 1x following stem cell transplantation resulting in a change of the blood group 1x in a patient after renal transplantation (patient BG 0, transplant BG A, plasma of BG 0 transfused by mistake). The stated cause was inadequate communication of specific transfusion requirements in post-transplant patients with complex blood group constellations (stem cell and solid organ transplants). In one case in which prbc of blood group 0-negative and FFP were ordered simultaneously in a case of massive transfusion, FFP of blood group 0 was issued by mistake. In a classical transfusion error, a fortuitously compatible PC was administered (see Case 14). In eight of the nine reported cases of antibody-incompatible transfusion, pre-existing but no longer detectable antibodies were not taken into account. In five of these cases the alloantibody was not known in the laboratory concerned. Three cases were due to a laboratory error (1x antibody screening test incorrectly interpreted and wrong antibody taken into account, 1x warning in laboratory information system (LIS) disregarded, 1x incorrect transmission of antibody results when changing LIS). In the remaining case cold agglutinins masked an existing antibody in the test performed prior to issue. This antibody was detected only by means of a subsequent further investigation and its specificity was found to be anti-f. In this situation mild or delayed haemolytic reactions are known to occur, however in the present case there was no evidence of any such reaction. In the 10 prbc transfusions: 6x patients mixed up at the time of administration (transfusion to the wrong patient), 1x with acute HTR 2x samples mixed up in the laboratory, resulting in the wrong blood group being determined for two patients with ensuing issue of one incompatible and one fortuitously compatible blood component (1x with acute HTR) 2x prbc of the wrong blood group (BG) issued after stem cell transplantation (the original BG instead of the new BG; in both cases no TR was observed)

16 14 Two cases in which untested prbc from emergency stocks were administered when no emergency situation existed should be regarded as transfusion errors. A further eight reports of administration of untested prbc in emergency situations and five cases of administration (in the setting of massive transfusion) of blood products known to be Rh-incompatible are strictly classifiable as IBCT (non-optimal blood product), but not as transfusion errors. In four cases immunohaematological (IH) testing after emergency transfusion of untested prbc yielded a positive antibody screen or a positive direct antiglobulin test (DAT). In these circumstances the possibility that a pre-existing antibody will be boosted must be accepted. In one of these cases a possible delayed HTR occurred. Selected cases of IBCT that resulted in a transfusion reaction are described in section 3.4 «Cases of IBCT». A common feature of all transfusion errors related to the ABO system is that, independently of the original deviation, the final barrier in the transfusion process failed to prevent the error. Had a final control (checking that the patient s blood group, surname, given name, and date of birth as stated on the label of the blood product to be transfused tally with the corresponding details on the patient s blood group card; checking the identity of the patient who is about to receive the transfusion immediately before the transfusion is started; and checking for correct assignment of the blood product to the patient) been correctly performed before the transfusion was started, these transfusion errors could have been prevented Near miss events Definition: an error or a deviation from standard operating procedures or directives which is discovered before initiation of a transfusion and which, had it not been detected, could have resulted in a transfusion error or a transfusion reaction in a recipient. The number of NMs reported was higher this year (619 events from 14 institutions) than in the previous year (467 reports from four hospitals). We still assume, however, that these figures are the proverbial tip of the iceberg. NM events can be analysed from various perspectives, and different conclusions can be drawn depending on how they are classified. The site in the transfusion chain at which the deviation was detected indicates sites of reliably functioning barriers (e.g. check on sample receipt in the laboratory). It is important that these safety-enhancing points in the transfusion chain be identified and that any planned changes to operating procedures at these points be made subject to particularly close scrutiny. Deviations can also be classified on the basis of their type into individual errors, system errors, or a combination of both these types. Higher priority is accorded to the search for weak points in the transfusion chain and to elimination of known system errors, since these are a latent risk and will inevitably cause harm sooner or later. For example, the practice of accepting and processing orders for blood products placed by telephone rather than in writing is certain to lead sooner or later to the issue of a wrong product due to a misunderstanding. The occurrence of individual errors due to carelessness cannot be reliably prevented. Efforts to deal with this problem must therefore be directed at creating framework conditions that make it more difficult to commit such errors in the future. An example of this is the «tan tube» blood group check performed at the Sunnybrook Health Sciences Centre in Toronto, Canada. This is a simple method of ensuring that a second, independent blood sample is obtained for the second blood group check. In this method, the sample material for the obligatory second blood group check has to be ordered separately and specifically in the laboratory. The sampling tubes used for this purpose have a cap of a colour (in this case tan, illustration 1) that is different from the sampling tubes in stock on the ward (which are used for the first determination). The laboratory supplies these tan tubes to the ward only in response to a request and only after initial blood typing has been performed in the laboratory in a plastic bag on which the procedure to be followed is shown. After the blood sample has been drawn, the filled sampling tube must be returned to the laboratory in the same bag for processing. The person responsible signs a special coloured sticker on the bag to confirm that he/she has personally checked the patient s identity and drawn the blood sample. This ensures that blood for the second blood group check cannot be drawn during the same sampling procedure as the sample for the first blood group determination.

17 15 Illustration 1 Table 10: Classification of events by site of deviation in transfusion chain Stage Number Comments, examples of most common deviations Preparation 505 including 309 associated with blood sampling for T&S and 102 associated with process deviations Laboratory 67 including 26 associated with storage and 28 associated with issue Administration Other 2 Total including 36 associated with handling or interim storage of blood products Reproduction by courtesy of Dr. Jeannie Callum, Director of Transfusion Medicine and Tissue Banks, Sunnybrook Health Sciences Centre, Toronto, Kanada. Analysis on the basis of the site in the transfusion chain at which the deviation occurred provides information on steps in the process that are susceptible to error and on missing or inadequately functioning barriers (e.g. patient identification). These findings raise the question of what measures have the potential to function as reliable means of preventing recurrence of the observed deviations.

18 16 Illustration 2 forms part of the «Error and risk analysis» (ERA) course run by «Patient Safety Switzerland» and was kindly made available to us by that body. The table serves as a basis for considering the relative strength and system relevance of the various possible measures. Translated from the original German Illustration 2: Stronger to weaker actions Strong Intermediate Weak 1. Architectural and physical plant changes 2. New plant, devices and equipment after usability testing 3. Technical controls and interlocks 4. Simplification of processes and removal of unnecessary steps 5. Standardisation of equipment, processes and sequence of treatment 6. Tangible involvement and action by leadership 1. Increase in staffing / decrease in workload 2. Software enhancement and modification 3. Elimination/reduction of distractions 1. Double checks 4. Checklists / cognitive aids 4. Training 5. Eliminate look- and sound-alikes 6. Read back / four-eyes principle 7. Extended documentation / intensified communication 8. Redundancy 2. Warnings and labels 3. New/additional procedures, memoranda, instructions and guidelines 5. Additional studies and analyses Adapted from: Departement of Veterans Affairs National Center for Patient Safety (NCPS)

19 17 In the analysis based on the type of event we classify NM reports into three main groups, namely «NMs in the narrow sense», «process deviations», and «errors in interim storage of blood components (handling and storage errors)». Near misses in the narrow sense (383 cases, 62% of NM reports) We use the term «near miss in the narrow sense» to refer to a deviation which, had it not been detected, could have resulted in a transfusion error. Table 11 Type of deviation Patient ID problems of administrative origin Mix-up of patients or samples when obtaining blood for pre-transfusion testing Number Comments (%) 12 (3%) E.g. name variants, incorrect recording of patient on admission, identity fraud, more than one set of medical records in the name of the same patient 50 (13%) 15 reports of patient mix-up, 7 of sample mix-up; other cases detected only on the basis of a blood group discrepancy from an earlier value, in which case sequence of events often not reconstructable Sampling error 9 (2%) Sample diluted, wrong type of tube used Labelling/inscription errors of all kinds 251 (66%) Labelling of samples and/or order absent, incorrect, discrepant, or with details of another patient Ordering errors 12 (3%) Wrong product ordered or product ordered for wrong patient, specification not observed/stated Issue 14 (4%) Wrong product, product for wrong patient, product with incorrect patient details, or expired/noncompliant product issued Laboratory error 18 (5%) Samples mixed up in laboratory, errors in transmission of results, result misinterpreted Communication 9 (2%) Information (about known antibodies, transfusion history) not passed on Other 8 (2%) Wrong unit of blood product collected Total 383 The proportion of all NM reports accounted for by «NMs in the narrow sense» was 5% less than in the previous year. As before, by far the most common errors of this type were incorrect labelling and inscription of the blood samples to be used for the pretransfusion investigations (blood typing, antibody screening test). The consequence of these errors is, that the blood sample concerned has to be discarded and a new sample ordered, since the blood sample cannot be attributed with certainty to the patient. Sample and patient mix-ups and labelling errors occur in similar fashion: sampling tubes are labelled in advance and then if the patient s identity is not checked blood is drawn from the wrong patient, or else a blood sample is taken in an unlabelled tube which is subsequently (in the nurses station) labelled with the personal details of another patient. It is therefore absolutely essential that both blood sampling for T&S and patient identification be performed in strict accordance with standard operating procedures (active patient identification, labelling of the sample at the bedside). Experience has shown that this needs to be emphasised and repeated again and again in order to make and keep the nurses who perform these tasks aware of the importance of repeated checking especially of patient identity for the prevention of mix-ups.

20 18 As aids to patient identification, hospitals are making increasing use of barcodes and RFID-based systems involving patient wristbands for electronic matching of data recorded on sampling tubes, patient wristbands, and blood products. The use of such systems simplifies and standardises procedures for obtaining blood for pre-transfusion investigations and for administering transfusions. This reduces the possibilities for error at these two critical stages. Process deviations (102 cases, 16% of NM reports) Process deviations are deviations from standard operating procedures that are discovered and documented via the quality assurance system for the use of labile blood products but which would not have led directly to a transfusion error even if they had not been discovered. Almost all the reports of this type were from a hospital in which an additional control system for patient identification had been introduced. This system is based on the use of a wristband and additional identification stickers in all patients who are to receive a transfusion. Where this additional identification of the blood samples for the pre-transfusion investigations and ordering of blood is incomplete or incorrect (e.g. no control sticker on sampling tube), the sample is rejected on receipt in the laboratory and the blood sampling has to be repeated. Other examples are incorrect completion of the coldchain certificate and the affixing of hospital-internal patient labels over existing labels on external samples. This wastage of blood product units could be reduced by a rule that although more than one product may be ordered for one patient, only one prbc unit should where the patient s condition and the laboratory s delivery times permit such a strategy be issued at any one time. Sixty-three reports referred to errors either in interim storage of issued blood components or in storage in the hospital s blood bank, e.g. blood products «lost» (listed as past expiration date in the inventory but physically untraceable; supposedly disposed of but not deleted from the electronic stock list) damaged blood bags (FFP during thawing, punctured bag) storage in unmonitored refrigerators or beyond expiration date prbc stored in freezer or warmed in FFP incubator instead of in warming coil This analysis is intended to show which errors of this type occur commonly and lead to avoidable loss of blood product units. In this way we hope to raise the awareness of blood transfusion workers and to encourage them to actively detect and analyse incidents of this kind in their institution in order to minimise the future occurrence of such errors. Incorrect interim storage of blood components (134 cases, 22% of NM reports) The number of reports relating to the handling and interim storage of blood components after issue was substantially higher in 2012 than in the previous year, the proportion of reports of this type rising from 12.5% in 2011 to 22% in Of these reports, 71 related to blood products that had been ordered or issued but then were not transfused. In five cases this was because the patient died or was transferred before the transfusion could be given or because the decision to give the patient a transfusion was reversed after the product had been issued. Most of the reports did not state why the blood product concerned was returned to the laboratory, where most of them had to be discarded (prbc warm, FFP thawed). This occurred in the case of 124 reports and led to the destruction of at least 170 blood products. A notable feature of many of these reports was that several products were ordered for the patient concerned and then all issued at the same time.

21 19 3. Sample case reports 3.1 Deaths In 2012 there were 10 reports of events in the course of which the patient died and where the temporal relationship was suggestive of a transfusion reaction. In three of these cases the autopsy showed causes of death that were not aetiologically related to the transfusion. In two cases retrospective analysis of the clinical course showed that events (pre-existing sepsis/aspiration and asystole, respectively) leading to the patient s death had been present before the transfusion. In four cases a causal relationship between death and the preceding transfusion could not be ruled out. These four cases included two anaphylactic reactions in complex, already life-threatening situations, one case of asystole with hyperkalaemia, and one of multiorgan failure with haemolysis of unknown cause (possible delayed HTR). Case 1: TACO An 82-year-old female patient was brought to a hospital accident and emergency department with predominantly left-sided acute heart failure (moist rattles in both lung fields, dyspnoea, chest x-ray showing cardiomegaly and evidence of fluid overload, BNP 4,582 pg/ml), moderately severe to severe renal failure, rheumatoid arthritis, and suspected infection. Diagnosed with «severe» anaemia (7.9 g/dl) she was transfused with one unit of prbc over two hours and 15 minutes. Still dyspnoeic, she was transferred to a ward, where 30 minutes later transfusion of a second unit of prbc was commenced. Half an hour later the patient was severely dyspnoeic, pale, and showed peripheral circulatory shutdown. An oxygen saturation of between 60% and 90% was measured with difficulty and blood pressure levels of over 150/70 mmhg were recorded. Fifteen minutes later an ICU doctor who had been called to see the patient found her to be severely dyspnoeic with unmeasurable oxygen saturation and rattles in both lung fields. Despite administration of furosemide, methylprednisolone, clemastine, and morphine the patient s consciousness became clouded (differential diagnosis: CO2 retention, opiate effect), her condition continued to deteriorate, and she died as a result of cardiovascular failure. This reaction was adjudged to be a probable case of transfusion-associated circulatory overload (TACO). Comment: We are not in a position to properly assess how pressing was the need for two units of prbc to be transfused in this situation, however the transfusion rate (1 unit of prbc with a volume of ml over a period of 135 minutes, equivalent to about 2 ml/min) was unquestionably too high for a patient with clinical evidence of significant pre-existing cardiac impairment. The rate should certainly have been no more than 1 ml/kg bodyweight/hour. Whether such a slower rate, possibly in conjunction with administration of diuretics before the first, or at the latest before the second transfusion, would have prevented the development of cardiovascular failure in this patient remains an open question. 3.2 Transfusion reactions of grade 3 severity In 2012 there were 16 reports of life-threatening TRs with high imputability. Of these 16 reactions, eight were severe allergic TRs (four anaphylactoid and four anaphylactic reactions), five were cases of circulatory overload, one was an acute haemolytic TR, one was a hypotensive TR, and one was a TRALI. Selected cases are described below. Case 2: TRALI About 30 minutes after receiving a transfusion of apheresis-derived platelet concentrate (PCa) a male patient with AML, born in 1949, abruptly developed dyspnoea and nausea, became pale, and was briefly unresponsive. His blood pressure was unmeasurable (cf. 117/69 mmhg before transfusion) and his oxygen saturation dropped to 85%. He regained consciousness spontaneously and was given hydrocortisone, clemastine, and oxygen. The dyspnoea persisted and auscultation of the lungs revealed coarse rattles. After the patient was transferred to the ICU for monitoring and given an inhalation of ipratropium + salbutamol his oxygen concentration rose to 97% within 10 hours and oxygen supplementation was suspended after 18 hours. No cardiac event could be demonstrated, a review of his case notes revealed no evidence of any discrepancies, and blood cultures from the patient and culture of the product showed no growth. The IgA level was within normal limits. A chest x-ray showed bilateral pulmonary infiltrates. A provisional diagnosis of TRALI was made and HLA antibody testing was performed. The donor plasma showed anti- HLA-A2 antibodies and the patient was found to be HLA-A2 positive. The differential diagnosis includes an anaphylactic TR and TRALI. An allergic aetiology is suggested by the rapid improvement that occurred, especially after inhalation of a bronchodilator, whereas the presence of bilateral pulmonary infiltrates and the demonstration of HLA-A2 antibodies in the donor