National Haemovigilance Programme

Transcription

1 National Haemovigilance Programme Annual Report 2013

2 Written by Dr Krishna Badami, Transfusion Medicine Specialist* Dr Daren Buhrkuhl, Transfusion Medicine Specialist* Dr Deepak Sadani, Transfusion Medicine Specialist* Mr John Dagger, Technical Advisor* Dr Peter Flanagan, National Medical Director *NZBS National Haemovigilance Group Acknowledgements Jillian Sinden, Executive Assistant Carolyn Jeffrey, Business Analyst, Information Services Contact details National Haemovigilance Office New Zealand Blood Service Private Bag 7904 Wellington 6242 Telephone: Facsimile: haemovigilance@nzblood.co.nz NZBS website: Disclaimer Haemovigilance has been declared a protected quality assurance activity under Section 54 of the Health Practitioners Competency Assurance Act 2003 as notified by the Health Practitioners Notice 2006, published in the New Zealand Gazette on 6 April The effect of this declaration is that subject to certain circumstances: Any information that becomes known solely as the result of Haemovigilance is confidential; and Any documents brought into existence solely for the purposes of Haemovigilance are confidential; and The persons who engage in Haemovigilance in good faith are immune from civil liability. NZ BLOOD SERVICE ANNUAL HAEMOVIGILANCE REPORT 2013

3 Contents Foreword 2 1. Introduction 3 2. Trends in Blood Component Transfusion in New Zealand 4 3. Recipients of Blood Components 5 4. Transfusion-related Adverse Events: Imputability 8 5. Transfusion-related Adverse Events: Severity Transfusion-related Adverse Events: Implicated Blood Components Transfusion-related Adverse Events: Reporting District Health Boards Febrile Non-Haemolytic Transfusion Reactions (FNHTR) Allergic Transfusion Reactions Acute Haemolytic Transfusion Reactions (AHTR) Transfusion-Related Acute Lung Injury (TRALI) Transfusion Associated Circulatory Overload (TACO) Transfusion-Associated Dyspnoea (TAD) Unclassifiable Complications of Transfusion (UCT) Hypotensive Transfusion Reaction Reports Involving Paediatric Patients Delayed Haemolytic / Serologic Transfusion Reactions (DHTR / DSTR) Adverse Events Associated with Fractionated Plasma Products Incorrect Blood Component Transfused (IBCT) Near Miss Events NZBS Wrong Blood in Tube (WBIT) Events Bacterial Monitoring of Platelet Concentrates Donor Infectious Disease Screening and Transfusion Transmitted Infections (TTI) Adverse Events Associated with Blood Donation Whole Blood Donor Vasovagal Survey Request Form and Sample Labelling Errors 55 Appendix I. Transfusion Related Adverse Event Notification Form 58 Appendix II. Notification of Adverse Reactions to Fractionated Blood Products 62 Appendix III. Reporting Adverse Events Relating to Blood Donation 64 Appendix IV. Donor Adverse Event Report Form 70 NZ BLOOD SERVICE ANNUAL HAEMOVIGILANCE REPORT

4 Foreword This is the 9th Annual Haemovigilance Report for New Zealand. The principle focus is improving the safety of blood collection and transfusion, and support for the programme remains strong. Accurate classification of adverse transfusion events is important and the valued contribution from healthcare professionals completing and submitting adverse event forms is recognised and appreciated. Subsequent requests for additional clinical information are met by an overwhelmingly positive response and this enthusiasm is heartening. The outcome of work specifically investigating further those events involving respiratory distress has led to an expanded section on transfusion-associated dyspnoea. Donor safety, increasingly being incorporated into the mandate of haemovigilance programmes internationally, has been part of NZ Haemovigilance since inception in Presented here are results of a survey looking at vasovagal reactions in whole blood donors. These events, occurring in up to 1 in 20 donors at a mobile site are, as the survey shows, underreported. Together with data on adverse events occurring during plateletpheresis, future work aims to look at the impact of various interventions in reducing the frequency of reactions in blood donors. International patient blood management guidelines continue to reflect an increasingly restrictive red cell transfusion policy. A similar trend is seen locally, with falling mean pre-transfusion haemoglobin values in the recipients of red cells reported to NZ Haemovigilance. The change in local clinical practice has contributed to a 14-15% decline in the number of annual red cell transfusions and annual total blood component use in NZ over the past 3-4 years. Largely as a result of these changing demand-patterns, the number of reported transfusion events has also declined by 20% since I would like to thank John Dagger who runs the Haemovigilance Office in Wellington, collates the data and who, once again, has played a major role in drafting the Annual Report. His support and effort throughout the year is greatly appreciated. I hope you will find the report informative and look forward to your on-going support of the programme. Dr Daren Buhrkuhl Transfusion Medicine Specialist NZBS Wellington 2 NZ BLOOD SERVICE ANNUAL HAEMOVIGILANCE REPORT 2013

5 1. Introduction COUNCIL OF EUROPE DEFINITION OF HAEMOVIGILANCE. The organised surveillance procedures related to serious or unexpected events or reactions in donors or recipients and the epidemiological follow up of donors The New Zealand National Haemovigilance Programme was established in This is the ninth Annual Haemovigilance Report for New Zealand. The National Haemovigilance Office receives reports from Blood Bank Scientists and Transfusion Nurse Specialists from hospitals within New Zealand. The reporting form (Appendix I) includes a severity scale, an imputability scale and definitions of transfusion-related adverse events (TRAE) based on those agreed upon by the International Society of Blood Transfusion s Working Party on Haemovigilance in collaboration with the International Haemovigilance Network (ISBT/IHN). All reports received at the Haemovigilance Office are reviewed by a Team comprising a number of Transfusion Medicine Specialists and an experienced Scientist who is also responsible for overall management of the scheme. Where required, additional information is sought from the submitter of the report in order to accurately classify the type of adverse event, imputability and severity scores. The data is entered into a secure database in which clinician and patient names are not included. Upon publication of the Annual Haemovigilance Report the paper records are destroyed and the unique patient identifier is then deleted from the database. The reporting of TRAE to the National Haemovigilance Programme is voluntary. During 2013 there were 507 events involving 483 patients; similar figures to those obtained since 2011 (Figure 1.1). Compared to 2010 however, there has been a 20% reduction in the total number of reported events. The year on year number of events and patients is shown in Figure 1.1. FIGURE 1.1 ANNUAL NUMBER OF TRANSFUSION-RELATED ADVERSE EVENTS Recipients Events Number Year (2005 total adjusted for 12 months) NZ BLOOD SERVICE ANNUAL HAEMOVIGILANCE REPORT

6 2. Trends in Blood Component Transfusion in New Zealand Table 2.1 shows the annual number of blood components transfused. Comparing the number of red cell units transfused in 2013 to the number transfused in 2010, there has been a 15.6% reduction. The rate of red cells transfused in 2013 is 24.8 / 1,000 of the New Zealand population. There has been a 41.2% increase in the number of units of cryoprecipitate units transfused which likely reflects the introduction of massive transfusion protocols in a number of hospitals. TABLE 2.1 ANNUAL NUMBER OF BLOOD COMPONENTS TRANSFUSED Blood Component (Rate / 1,000 population) Red Cells 123, , , , ,565 Red Cells Neo 1,840 1,898 1,749 1,732 1,664 % Change compared To 2010 Total Red Cells 125, , , , ,229 (24.8) -15.6% Platelets - APH 7,571 7,576 6,661 2, Platelets - Pooled 5,325 5,403 2, Platelets - APH PAS 774 5,354 5,627 Platelets - Pooled PAS 48 2,988 5,037 6,457 Platelets - Neo Total Platelets 13,381 13,616 13,257 13,783 13,388 (3.2) -1.7% Fresh Frozen Plasma 19,874 17,685 16,736 16,524 13,528 Fresh Frozen Plasma Neo Total Fresh Frozen Plasma 20,001 17,872 16,863 16,724 13,703 (3.2) -23.3% Cryoprecipitate 2,869 2,951 3,228 3,745 4, % Cryodepleted Plasma Total Components 162, , , , ,995 (32.3) -14.1% The decrease in the number of red cell units transfused is also observed in the decrease in the number of recipients of red cells (Table 2.2). Compared to 2010, there has been a 11.2% reduction in the number of recipients of red cells. TABLE 2.2 ANNUAL NUMBER OF RED CELL RECIPIENTS Year Number Red Cell Recipients (% Change from 2010) , , ,101 (-3.7%) ,673 (-5.2%) ,978 (-11.2%) 4 NZ BLOOD SERVICE ANNUAL HAEMOVIGILANCE REPORT 2013

7 3. Recipients of Blood Components Table 3.1 below provides information on the recipients of red cell, platelet and FFP blood components transfused during TABLE 3.1 RECIPIENTS OF BLOOD COMPONENTS 2013 Blood Component Red Cells Platelets FFP Recipient Gender (Number) Female 14,266 1,208 1,259 Male 10,672 2,061 1,911 Unknown Total 24,978 3,272 3,172 Recipient Age (Years) Mean Median Maximum Minimum Units Transfused Per Recipient Total During 2013 Mean Median Maximum Minimum Further detail on the recipients of blood components and the type of blood components transfused during 2013 is shown in Table 3.2. TABLE 3.2 Component RECIPIENTS OF BLOOD COMPONENTS 2013 BY AGE GROUP AND BLOOD COMPONENT TYPE Age Group (years) 0-1mth 1mth Red cells 1.6% 2.6% 1.2% 4.0% 5.8% 6.0% 8.2% 12.5% 20.1% 22.5% 15.5% FFP 2.4% 2.2% 1.2% 4.5% 3.9% 6.1% 10.2% 16.8% 22.7% 21.9% 8.1% Cryoprecipitate 8.1% 8.9% 2.4% 5.3% 4.5% 6.5% 8.8% 16.4% 19.8% 16.2% 3.0% Platelets 4.3% 6.9% 3.5% 4.4% 3.6% 5.2% 10.0% 19.3% 22.9% 15.6% 4.3% Cryodepleted 0.0% 0.0% 0.0% 25.0% 16.7% 16.7% 25.0% 0.0% 8.3% 8.3% 0.0% All Components 2.1% 3.2% 1.5% 4.2% 5.4% 5.9% 8.6% 13.7% 20.6% 21.5% 13.2% NZ BLOOD SERVICE ANNUAL HAEMOVIGILANCE REPORT

8 3. Recipients of Blood Components continued Table 3.3 and Figure 3.1 show the age distribution of recipients of blood components compared to that of the New Zealand population. Recipients 65 years old constitute 55% of recipients of blood components. In contrast, 14% of the New Zealand population are 65 years old. TABLE 3.3 RECIPIENTS OF BLOOD COMPONENTS 2013 BY AGE GROUP AND COMPARED TO THE NEW ZEALAND POPULATION Age Group (Years) Number Transfusion Recipients 32, % 1.5% 4.2% 5.4% 5.9% 8.6% 13.7% 20.6% 21.5% 13.2% NZ Population 1 4,242, % 13.5% 13.8% 12.1% 13.5% 14.2% 11.6% 8.2% 4.4% 1.7% 1 New Zealand 2013 Population Census. Statistics New Zealand ( FIGURE 3.1 RECIPIENTS OF BLOOD COMPONENTS 2013 BY AGE GROUP AND COMPARED TO THE NEW ZEALAND POPULATION Tranfusion Recipients (n=32,703) NZ Population (n=4,242,051) Age Group (Years) Percentage Percentage 6 NZ BLOOD SERVICE ANNUAL HAEMOVIGILANCE REPORT 2013

9 3. Recipients of Blood Components continued Table 3.4 and Figure 3.2 show the yearly mean pre-transfusion haemoglobin concentration for recipients of red cells where an adverse event was reported. There has been a significant decrease (p = <0.001) from 2006 (81.5 g/l) to 2013 (77.7 g/l). TABLE 3.4 YEARLY MEAN PRE-TRANSFUSION HAEMOGLOBIN CONCENTRATION Year Number Mean Hb g/l SD FIGURE 3.2 YEARLY MEAN PRE-TRANSFUSION HAEMOGLOBIN CONCENTRATION Mean Haemoglobin g/l Year NZ BLOOD SERVICE ANNUAL HAEMOVIGILANCE REPORT

10 4. Transfusion-Related Adverse Events: Imputability During 2013, a total of 507 transfusion-related adverse events were reported to the National Haemovigilance programme. A total of 71 (14.0%) had a low 2 imputability score and were excluded from the analysis since they were unlikely to be attributable to transfusion. Excluded events were predominantly FNHTR and unclassifiable complications of transfusion (UCT). Imputability score definitions (ISBT/IHN) are provided in Table 4.1. TABLE 4.1 IMPUTABILITY SCORE DEFINITIONS Imputability Score Definitions NA Not assessable When there is insufficient data for imputability assessment. 1 Excluded 2 Unlikely 3 Possible When there is conclusive evidence beyond reasonable doubt for attributing the event to alternative causes. When the evidence is clearly in favour of attributing the event to causes other than transfusion. When the evidence is indeterminate for attributing the event either to the transfusion or alternative causes. 4 Likely, probable When the evidence is clearly in favour of attributing the event to the transfusion. 5 Certain When there is conclusive evidence beyond reasonable doubt for attributing the event to the transfusion. The number of reported events excluded due to low 2 imputability per year are shown in Table 4.2. TABLE 4.2 TRANSFUSION-RELATED ADVERSE EVENTS OF LOW 2 IMPUTABILITY Total Events Number of Imputability Percentage 14.0% 11.9% 12.6% 14.0% 16.9% 14.0% 8 NZ BLOOD SERVICE ANNUAL HAEMOVIGILANCE REPORT 2013

11 4. Transfusion-Related Adverse Events: Imputability continued Table 4.3 shows all reported events in 2013 by event type and imputability score. TABLE 4.3 Event Type TRANSFUSION-RELATED ADVERSE EVENTS 2013 BY EVENT TYPE AND IMPUTABILITY SCORE Imputability Score Total Total 3 FNHTR Allergic UCT TAD IBCT TACO DSTR Near Miss Hypotension DHTR AHTR TRALI Total Percentage Events 7.3% 6.7% 50.3% 26.0% 9.7% 86.0% Data analysed and included in the remainder of the Annual Haemovigilance Report is for events of imputability 3 only. Figure 4.1 and 4.2 show the distribution of the 436 events (imputability 3) by event type. Febrile non-haemolytic and allergic transfusion reactions are the most frequently reported events. NZ BLOOD SERVICE ANNUAL HAEMOVIGILANCE REPORT

12 4. Transfusion-Related Adverse Events: Imputability continued FIGURE 4.1 TRANSFUSION-RELATED ADVERSE EVENTS (IMPUTABILITY 3) 2013 BY EVENT TYPE Number of Events FNHTR Allergic UCT TAD IBCT 16 TACO DSTR Near Miss Hypotension DHTR AHTR TRALI Adverse Event Type Key: FNHTR Allergic TACO IBCT UCT TAD DSTR DHTR AHTR TRALI Febrile non-haemolytic transfusion reaction Allergic transfusion reaction Transfusion-associated circulatory overload Incorrect blood component transfused Unclassifiable complication of transfusion Transfusion-associated dyspnoea Delayed serologic transfusion reaction Delayed haemolytic transfusion reaction Acute haemolytic transfusion reaction Transfusion-related acute lung injury 10 NZ BLOOD SERVICE ANNUAL HAEMOVIGILANCE REPORT 2013

13 4. Transfusion-Related Adverse Events: Imputability continued FIGURE 4.2 TRANSFUSION-RELATED ADVERSE EVENTS (IMPUTABILITY 3) 2013 BY EVENT TYPE Hypotension, 0.5% DHTR, 0.5% Near Miss, 2.5% DSTR, 2.8% AHTR, 0.2% TRALI, 0.2% TACO, 3.7% IBCT, 5.7% TAD, 6.0% FNHTR, 44.7% UCT, 6.7% Allergic, 26.8% There were 403 transfusion recipients associated with the 436 reported events included in the analysis. Table 4.4 shows the events by recipient gender along with data on recipient age. TABLE 4.4 TRANSFUSION-RELATED ADVERSE EVENTS (IMPUTABILITY 3) 2013 BY RECIPIENT GENDER Number Age (years) Mean Minimum Maximum Female month 97 Male months 97 Total month 97 Multiple transfusion-related adverse events were reported in 29 patients (Table 4.5). TABLE 4.5 NUMBER OF RECIPIENTS HAVING MULTIPLE TRANSFUSION-RELATED ADVERSE EVENTS (IMPUTABILITY 3) 2013 Total Events 1 Event 2 Events 3 Events Recipient Number NZ BLOOD SERVICE ANNUAL HAEMOVIGILANCE REPORT

14 5. Transfusion-Related Adverse Events: Severity The severity score definitions for transfusion-related adverse events developed by ISBT/IHN are shown in Table % of reported events of imputability score 3 were assessed as non-severe (grade 1). Severe (grade 2) events were 6.4% of all events and 64% of these were either allergic or TACO in nature (Table 5.2). There was one TACO reaction resulting in death (grade 4) in a 93 year old female. TABLE 5.1 SEVERITY SCORE DEFINITIONS FOR TRANSFUSION-RELATED ADVERSE EVENTS 2013 Grade 1 Grade 2 (severe) The recipient may have required treatment but lack of such would not have resulted in permanent damage or impairment of a body function. The recipient required hospitalisation or prolongation of hospitalisation directly attributable to the event; and/or the adverse event resulted in persistent or significant disability or incapacity; or the event necessitated medical or surgical intervention to preclude permanent damage or impairment. Grade 3 (life-threatening) Grade 4 (death) The recipient required major intervention following the transfusion (e.g. vasopressors, intubation, transfer to intensive care) to prevent death. The recipient died following an adverse transfusion reaction. Grade 4 should only be used if death is probably or definitely related to transfusion. If the patient died of another cause, the severity should be graded as 1, 2 or 3. TABLE 5.2 Event Type TRANSFUSION-RELATED ADVERSE EVENTS (IMPUTABILITY 3) 2013 BY EVENT TYPE AND SEVERITY Severity Grade 1 Grade 2 Grade 3 Grade 4 Total FNHTR Allergic UCT TAD IBCT TACO DSTR Near Miss Hypotension DHTR AHTR 1 1 TRALI 1 1 Total Percentage Events 92.5% 6.2% 1.1% 0.2% 12 NZ BLOOD SERVICE ANNUAL HAEMOVIGILANCE REPORT 2013

15 6. Transfusion-Related Adverse Events: Implicated Blood Components A total of 136,995 blood component units were transfused in Of these, 445 units were implicated in the 436 reported adverse events. The overall adverse event rate in 2013 was 1 in 308 units transfused (32.5 per 10,000 units transfused, 95% CI 30 to 36). Table 6.1 shows the adverse event rate for the individual blood component types. TABLE 6.1 TRANSFUSION-RELATED ADVERSE EVENTS (IMPUTABILITY 3) 2013 BY BLOOD COMPONENT TYPE Units Implicated in TRAE 1 Units Transfused Frequency Rate / 10,000 Units Transfused (95%CI) Cryodepleted Plasma : (23.0 to 208.3) Platelets Apheresis PAS 27 5,627 1: (32.7 to 70.0) Platelets Pooled PAS 24 6,457 1: (24.7 to 55.5) Red Cells ,229 1: (29.2 to 36.1) Fresh Frozen Plasma 38 13,703 1: (20.1 to 38.1) Cryoprecipitate 8 4,167 1: (9.0 to 38.6) Platelets Apheresis Plasma 2 2 1,304 1: (0.3 to 59.8) Total ,995 1: (29.6 to 35.6) 1 Includes TRAE where multiple component types transfused. 2 Includes 817 units Platelets - Neonatal. NZ BLOOD SERVICE ANNUAL HAEMOVIGILANCE REPORT

16 6. Transfusion-Related Adverse Events: Implicated Blood Components continued Table 6.2 provides detail on the adverse events by the event type and type of blood component involved. TABLE 6.2 TRANSFUSION-RELATED ADVERSE EVENTS (IMPUTABILITY SCORE 3) 2013 BY EVENT TYPE AND BLOOD COMPONENT TYPE Red Cells Fresh Frozen Plasma Platelets Apheresis PAS Platelets Apheresis PAS Platelets Pooled Cryoprecipitate Cryodepleted Plasma Fractionated Plasma Products 2 Multiple Components Other 1 Number Units Transfused 105,229 13,703 1,304 5,627 6,457 4, FNHTR Allergic TAD UCT DSTR 12 IBCT TACO Near Miss DHTR 2 AHTR 1 Hypotension 1 1 TRALI 1 Total Events associated with transfusion of: allogeneic serum eye drops (2), granulocytes, autologous salvage red cells, autologous haematopoietic progenitor cells and matched unrelated-donor haematopoietic progenitor cells. 2 Events, other than ICBT and near miss, associated with fractionated plasma products are detailed in Chapter NZ BLOOD SERVICE ANNUAL HAEMOVIGILANCE REPORT 2013

17 7. Transfusion-Related Adverse Events: Reporting District Health Boards During 2013, transfusion-related adverse events were reported from all 20 District Health Boards in New Zealand. The number of events of imputability 3 per District Health Board and the event rate per 10,000 component units transfused are shown in Table 7.1 and Figure 7.1. The 2013 national adverse event rate was 31.8 per 10,000 component units transfused and was similar to that reported in 2012 (29.5 per 10,000 component units transfused). TABLE 7.1 TRANSFUSION-RELATED ADVERSE EVENTS (IMPUTABILITY 3) 2013 BY REPORTING DISTRICT HEALTH BOARD District Health Board Events Units Transfused Frequency Rate / 10,000 Units Transfused (95%CI) Southern DHB 40 7,595 1: (38.5 to 71.8) South Canterbury DHB 7 1,341 1: (22.9 to 109.7) MidCentral DHB 31 5,981 1: (36.3 to 73.7) Waikato DHB 71 15,429 1: (36.4 to 58.1) Tairawhiti DHB : (12.8 to 117.2) Lakes DHB 8 1,957 1: (19.2 to 82.0) Hutt Valley DHB 11 2,834 1: (20.8 to 70.3) Canterbury DHB 58 15,538 1: (28.8 to 48.3) Taranaki DHB 8 2,266 1: (16.6 to 70.8) Capital and Coast DHB 44 12,497 1: (26.1 to 47.3) Counties Manukau DHB 45 12,882 1: (26.0 to 46.8) Bay of Plenty DHB 19 5,964 1: (20.1 to 50.1) West Coast DHB : (0.8 to 115.6) Wairarapa DHB 3 1,110 1: (5.2 to 83.1) Northland DHB 9 3,339 1: (13.3 to 52.0) Whanganui DHB 2 1,021 1: (0.5 to 76.1) Auckland DHB 53 29,456 1: (13.7 to 23.6) Hawkes Bay DHB 6 3,495 1: (6.9 to 38.4) Nelson Marlborough DHB 4 3,338 1: (3.5 to 32.0) Waitemata DHB 11 9,375 1: (6.3 to 21.3) Total ,995 1: (29.0 to 35.0) NZ BLOOD SERVICE ANNUAL HAEMOVIGILANCE REPORT

18 7. Transfusion-Related Adverse Events: Reporting District Health Boards continued FIGURE 7.2 TRANSFUSION-RELATED ADVERSE EVENTS (IMPUTABILITY 3) 2013 PER 10,000 COMPONENT UNITS TRANSFUSED BY REPORTING DISTRICT HEALTH BOARD Upper/Lower 95% CI Rate / 10,000 Component Units Transfused 140 Events / 10,000 Component Units Transfused Southern South Canterbury MidCentral Waikato Tairawhiti Lakes Hutt Valley Canterbury Taranaki Capital and Coast Counties Manukau Bay of Plenty West Coast Wairarapa Northland Whanganui Auckland Hawkes Bay Nelson Marlborough Waitemata Total 0 District Health Board 16 NZ BLOOD SERVICE ANNUAL HAEMOVIGILANCE REPORT 2013

19 8. Febrile Non-Haemolytic Transfusion Reactions (FNHTR) DEFINITION Fever ( 38 C and a change of 1 C from pre-transfusion value) and/or chills/rigors occurring during or within 4 hours of transfusion without any other cause such as haemolytic transfusion reaction, bacterial contamination or underlying condition. Febrile reactions were the most frequently reported type of transfusion-related adverse event (45%). A total of 215 reports of FNHTR were received, 195 were of imputability 3 and included in the analysis. The remaining 20 were of low 2 imputability and probably due to the patient s underlying medical condition. An additional 30 submitted reports of febrile reactions did not meet criteria for FNHTR and thus were not accepted by the Haemovigilance Programme. Table 8.1 shows FNHTR events by recipient gender along with data on recipient age. TABLE 8.1 FNHTR EVENTS (IMPUTABILITY 3) 2013 BY RECIPIENT GENDER Number Age (years) Mean Minimum Maximum Female days 97 Male All days 97 Comparing the age distribution of recipients experiencing FNHTR to that of recipients of all blood components, there is a significant reduction in frequency of FNHTR in the age groups 0 15 years and 85 years. There is an increase in FNHTR frequency in the year old group (Table 8.2). TABLE 8.2 FNHTR EVENTS (IMPUTABILITY 3) 2013 BY RECIPIENT AGE GROUP AND COMPARED TO RECIPIENTS OF ALL BLOOD COMPONENTS Age Group FNHTR All Blood Component Recipients Number Percentage Number Percentage p value 0-15 years 4 1.5% 2, % years % 1, % NS years % 6, % years % 18, % NS 85 years % 4, % Total ,703 NZ BLOOD SERVICE ANNUAL HAEMOVIGILANCE REPORT

20 8. Febrile Non-Haemolytic Transfusion Reactions (FNHTR) continued In addition to fever and chills/rigors, other clinical features associated with FNHTR are summarised in Table 8.3. An increase in blood pressure was noted in 16% of recipients with FNHTR. TABLE 8.3 FNHTR EVENTS (IMPUTABILITY 3) 2013 BY ASSOCIATED SIGNS AND SYMPTOMS Number % Events Symptom Female Male Total Female Male Total (n=91) (n=104) (n=105) Chills / Rigors % 50.0% 40.0% p value Increase in blood pressure % 25.0% 15.8% Flushing % 20.2% 13.2% Restlessness / Anxiety % 11.5% 11.7% 0.04 Dyspnoea % 12.5% 6.4% 0.02 Tachycardia % 9.6% 6.0% Nausea % 2.9% 2.6% Fall in blood pressure % 1.9% 2.3% Hypoxaemia % 2.9% 1.9% Mean temperature rise 2 C 2 C Of the reported FNHTR events, 16 met ISBT criteria for serious FNHTR. The ISBT Working Party on Haemovigilance (July 2011) defines FNHTR as serious when accompanied by: Fever 39 C oral (or equivalent) and a change of 2 C from pre-transfusion value, and chills/rigors. Table 8.4 shows serious FNHTR events by recipient gender along with data on change in temperature and recipient age. TABLE 8.4 SERIOUS FNHTR EVENTS (IMPUTABILITY 3) 2013 BY RECIPIENT GENDER Number Temperature Rise ( C) Age (Years) Mean Min Max Mean Min Max Female Male Total NZ BLOOD SERVICE ANNUAL HAEMOVIGILANCE REPORT 2013

21 9. Allergic Transfusion Reactions DEFINITION Mucocutaneous signs and symptoms during or within 4 hours of transfusion: morbilliform rash with pruritus, urticaria, localised angioedema, oedema of lips, tongue and uvula, periorbital pruritus, erythema and oedema, conjunctival oedema. Anaphylactic reaction is when, in addition to mucocutaneous symptoms, there is airway compromise or cardiovascular involvement. Laryngeal symptoms include throat tightness, dysphagia, dysphonia, hoarseness, stridor. Pulmonary symptoms include dyspnoea, cough, wheeze/ bronchospasm, hypoxaemia. Cardiovascular symptoms include hypotension, syncope. Allergic reactions are frequently reported after blood transfusions. They are most often mild reactions but may cause significant distress to recipients of blood transfusions and occasionally even significant morbidity. During 2013, 117 (27%) events were classified as allergic in nature. 106 (91%) of the allergic events were non-severe and the remaining 11 (9%) were severe or life-threatening. Table 9.1 shows allergic events by recipient gender along with data on recipient age. TABLE 9.1 ALLERGIC EVENTS (IMPUTABILITY 3) 2013 BY RECIPIENT GENDER Age (years) Number Mean Minimum Maximum Female Male mths 96 Total mths 96 Table 9.2 shows recipient age distribution for reported allergic events compared to that of all blood transfusion recipients. Allergic events are reported disproportionately more in the 0 24 years group and less in the 85 years group. TABLE 9.2 ALLERGIC EVENTS (IMPUTABILITY 3) 2013 BY RECIPIENT AGE GROUP AND COMPARED TO ALL BLOOD COMPONENT RECIPIENTS Allergic Events All Blood Component Recipients Age Group Number Percentage Number Percentage p value 0-15 years % 2, % < years % 1, % years % 6, % NS years % 18, % years 5 4.3% 4, % <0.001 Total ,703 NZ BLOOD SERVICE ANNUAL HAEMOVIGILANCE REPORT

22 9. Allergic Transfusion Reactions continued The information on recipient age distribution for reported allergic events is shown in Table 9.3 and Table 9.4 with the events involving typically plasma-rich components separated from plasma-poor red cell components. TABLE 9.3 PLATELET-, FRESH FROZEN PLASMA- AND CRYOPRECIPITATE-RELATED ALLERGIC EVENTS (IMPUTABILITY 3) 2013 BY RECIPIENT AGE GROUP AND COMPARED TO ALL RECIPIENTS OF SUCH COMPONENTS Allergic Events Platelet/ Plasma All Recipients Platelet/Plasma Number Percentage Number Percentage p value 0-1 mth % 1 mth - 4 years 3 5.3% % NS 5-15 years 4 7.0% % years % % years 3 5.3% % NS years 2 3.5% % NS years % % NS years % 1, % NS years % 1, % NS years 3 5.3% 1, % years 0 0.0% % Total 57 7,596 TABLE 9.4 RED CELL-RELATED ALLERGIC EVENTS (IMPUTABILITY 3) 2013 BY RECIPIENT AGE GROUP AND COMPARED TO ALL RECIPIENTS OF RED CELLS Allergic Events Red Cells All Recipients Red Cells Number Percentage Number Percentage p value 0-1 mth % 1 mth - 4 years 5 6.3% % years 7 8.9% % < years 4 5.1% 1, % NS years % 1, % NS years 3 3.8% 1, % NS years 5 6.3% 2, % NS years % 3, % NS years % 5, % years % 5, % NS 85 years % 3, % NS Total 79 25, NZ BLOOD SERVICE ANNUAL HAEMOVIGILANCE REPORT 2013

23 9. Allergic Transfusion Reactions continued Table 9.5 provides information on signs and symptoms associated with allergic events with non-severe (grade 1) reactions compared to severe and life threatening (grade 2 and 3) reactions. A fall in blood pressure, dyspnoea and tachycardia were key indicators of more severe reactions. TABLE 9.5. ALLERGIC EVENTS (IMPUTABILITY 3) 2013 BY ASSOCIATED SIGNS AND SYMPTOMS Symptom Number Grade 1 (n=106) % Symptoms Allergic Events % Grade 1 Events Number Grade 2 & 3 (n=11) % Symptoms % Grade 2 & 3 Events p value Urticaria % 68.9% % 90.9% NS Non-urticarial rash % 18.9% 0 0.0% 0.0% Restlessness / Anxiety % 12.3% % 36.4% 0.05 Stridor / wheeze % 10.4% 3 8.3% 27.3% NS Facial oedema % 10.4% 3 8.3% 27.3% NS Increase in blood pressure % 9.4% 0 0.0% 0.0% Flushing 6 3.8% 5.7% 2 5.6% 18.2% NS Fall in blood pressure 4 2.5% 3.8% % 36.4% Cough 4 2.5% 3.8% 2 5.6% 18.2% NS Chills / Rigors 3 1.9% 2.8% 2 5.6% 18.2% NS Dyspnoea 3 1.9% 2.8% 3 8.3% 27.3% 0.01 Tachycardia 1 0.6% 0.9% 3 8.3% 27.3% Multiple allergic events were reported in 6 patients as shown in Table 9.6. TABLE 9.6 NUMBER OF RECIPIENTS HAVING MULTIPLE ALLERGIC EVENTS (IMPUTABILITY 3) 2013 Allergic Events Total Events 1 Event 2 Events Number of Recipients The implicated blood components transfused and the clinical indication/diagnosis for transfusion of those 6 patients with multiple allergic events is detailed in Table 9.7. TABLE 9.7 MULTIPLE ALLERGIC EVENTS (IMPUTABILITY 3) 2013 BY BLOOD COMPONENT TYPE Number Events Implicated Components Diagnosis Patient 1 2 Red cells Post laparotomy Patient 2 2 Fresh frozen plasma Plasma exchange Patient 3 2 Fresh frozen plasma Plasma exchange Patient 4 2 Cryodepleted plasma Plasma exchange Patient 5 2 Red cells Beta thalassaemia major Patient 6 2 Pooled PAS platelets. Fresh frozen plasma AML NZ BLOOD SERVICE ANNUAL HAEMOVIGILANCE REPORT

24 9. Allergic Transfusion Reactions continued The frequency of allergic events and, for those events where a single blood component was implicated, the rate per 10,000 component units transfused is shown in Table 9.8. TABLE 9.8 ALLERGIC EVENTS (IMPUTABILITY 3) 2013 BY BLOOD COMPONENT TYPE Component Number Events Number Units Transfused Frequency Rate / 10,000 Units Transfused (95%CI) Cryodepleted plasma : (23.0 to 208.3) Fresh frozen plasma 22 13,703 1: (10.5 to 24.4) Platelets Apheresis Plasma 2 1,304 1: (0.3 to 59.6) Platelets Apheresis PAS 7 5,627 1: (5.5 to 28.2) Platelets pooled PAS 8 6,457 1: (5.8 to 24.9) Cryoprecipitate 3 4,167 1:1, (1.4 to 22.2) Red cells ,229 1:1, (4.8 to 7.8) Total ,995 1:1, (6.7 to 9.7) NZBS commenced introduction of pooled platelets suspended in Platelet Additive Solution (PAS) in late 2010 and apheresis PAS platelets in This significant change in production method was made with the specific purpose of reducing the amount of plasma in platelets. The expected benefits from this change were both the recovery of additional plasma for fractionation and a reduction in the frequency of allergic reactions to platelets. The haemovigilance data indicates that this latter goal has been achieved. Table 9.9 compares the number of allergic events for the different platelet component types There is a significant reduction (p = 0.001) in the rate of allergic events with platelets suspended in PAS compared to platelets suspended in plasma. There is no significant difference (p = 0.48) in the rate of allergic events with apheresis or pooled platelets suspended in PAS. TABLE 9.9 PLATELET-RELATED ALLERGIC EVENTS (IMPUTABILITY 3) Platelet Component Type Number Events Number Units Transfused Frequency Rate / 10,000 Units Transfused (95%CI) Apheresis Plasma ,768 1: (3.1 to 4.3) Pooled Plasma 89 23,597 1: (3.1 to 4.6) Apheresis PAS 18 11,755 1: (1.0 to 2.4) Pooled PAS 22 14,530 1: (1.0 to 2.3) All Plasma Platelets ,365 1: (3.3 to 4.2) All PAS Platelets 40 26,285 1: (1.1 to 2.1) Total ,650 1: (2.7 to 3.5) 1 Includes Platelets - Neonatal. 22 NZ BLOOD SERVICE ANNUAL HAEMOVIGILANCE REPORT 2013

25 10. Acute Haemolytic Transfusion Reactions (AHTR) DEFINITION A reaction in which symptoms and clinical or laboratory signs of increased red cell destruction occur at any time up to 24 hours following the transfusion of blood or a blood component. The major concern in evaluating acute reactions is exclusion of bacterial contamination of a blood component or haemolysis due to the transfusion of immunologically incompatible red cells. Acute haemolytic transfusion reactions may also occur due to mechanical red cell destruction. Features of a haemolytic transfusion reaction include: Fever, tachycardia, change in blood pressure, flank or back pain Inadequate rise in haemoglobin after the transfusion or a drop in haemoglobin Rise in LDH, bilirubin Haemoglobinura Decrease in haptoglobin There was one reported event during 2013 classified as an acute haemolytic transfusion reaction. The details are provided below. CASE A A 50 year old male with metastatic clear cell renal carcinoma was admitted due to fever following a cycle of chemotherapy and was treated with ceftriaxone antibiotic. The patient was transfused with one unit of red cells. One hour following the commencement of this transfusion the patient complained of rigors and that he just felt rotten. The patient s pre-transfusion haemoglobin was 76 g/l and bilirubin 9 μmol/l. Two hours after the reported reaction the haemoglobin was 63 g/l and bilirubin 26 μmol/l. Four hours after the reaction the bilirubin had risen to 37 μmol/l. Samples were referred to the local blood bank for investigation of the adverse transfusion-related event: The appearance of the pre- and post-transfusion samples and the donor unit was normal. Pre- and post-transfusion samples grouped as O RhD positive, red cell antibody screen confirmed as negative. The direct antiglobulin test (DAT) on pre- and post-transfusion samples was positive. No antibody eluted. Red cell unit group O RhD positive, DAT negative. Patient s pre-transfusion compatibility test negative, post-transfusion sample incompatible by indirect antiglobulin test (IAT). Patient samples were referred to the National Red Cell Reference Laboratory which reported a ceftriaxone-dependent antibody. A positive DAT and negative eluate is a classic finding with drug-dependent antibodies mediating druginduced haemolytic anaemia. The imputability score was classified as likely/probable and the severity grade as 2 (severe). Immune-mediated haemolytic anaemia has been observed in patients receiving cephalosporin class antibacterials. Severe cases of haemolytic anaemia, including fatalities, have been reported during treatment in both adults and children. NZ BLOOD SERVICE ANNUAL HAEMOVIGILANCE REPORT

26 11. Transfusion-Related Acute Lung Injury (TRALI) DEFINITION New acute lung injury (ALI): acute onset during or within 6 hours of completion of transfusion, hypoxaemia (PaO 2 /FiO 2 < 300 mmhg, oxygen saturation < 90% on room air, or other clinical evidence), bilateral infiltrates on frontal chest radiograph, no left atrial hypertension or other evidence of circulatory overload, no temporal relationship to an alternative risk factor for ALI. During 2013 there was one reported event of TRALI in New Zealand. The case is summarised below: CASE B A 44 year old female was admitted with alcoholic pancreatitis complicated by a pancreatic pseudocyst. The patient had a resolving sepsis, cultures positive for E. coli and enterococcus, and was now afebrile. Prior to CT-guided intervention for a blocked abdominal drain, she was transfused for a haemoglobin of 89 g/l. Within 6 hours of the commencement of the transfusion she became febrile (temperature rise from 37.7 C to 38.4 C), tachycardic (heart rate increased from 101 to 157 beats per minute) and hypoxaemic (Sa0 2 fell from 99% to 89%). The chest x-ray showed extensive air space and interstitial pulmonary oedema. The patient was transferred from the surgical unit to intensive care for respiratory support and monitoring. Invasive ventilation was not required. This patient was transfused with one unit of red cells. The red cell unit was donated by a female blood donor. The donor was investigated for HLA antibodies and high titre anti-hla-a24 + B40 + DR4, reactive against the recipient s HLA antigens, were identified. The implicated donor has been retired. The imputability score was classified as likely/ probable and the severity grade as 2 (severe). Figure 10.1 shows the number of TRALI events reported each year since Overall, the number of reported events has declined. NZBS has implemented a number of measures to reduce the risk of TRALI. Production of clinical FFP from male-only donors was implemented in 2008 and thereafter HLA-antibody screening of female plateletpheresis donors in July The male-only policy was extended to include cryoprecipitate and cryodepleted plasma by FIGURE 10.1 ANNUAL NUMBER OF TRALI EVENTS Male only FFP 9 8 HLA screening of platelets TRALI Events Year 24 NZ BLOOD SERVICE ANNUAL HAEMOVIGILANCE REPORT 2013

27 12. Transfusion Associated Circulatory Overload (TACO) DEFINITION Any 4 of the following occurring within 6 hours of completion of transfusion: acute respiratory distress, tachycardia, increased blood pressure, acute or worsening pulmonary oedema on frontal chest radiograph, evidence of positive fluid balance. An elevated BNP may be supportive of TACO. During 2013, there were 16 reported TACO events (3.7% of total events). Seven (44%) were non-severe, 7 (44%) were severe, 1 was life-threatening and 1 was implicated in the death of a patient. Table 12.1 shows the TACO events by recipient gender along with data on recipient age. TABLE 12.1 TACO EVENTS (IMPUTABILITY 3) 2013 BY RECIPIENT GENDER Number Age (Years) Mean Minimum Maximum Female Male All Table 12.2 shows the clinical features of the TACO events reported during TABLE 12.2 TACO EVENTS (IMPUTABILITY 3) 2013 BY ASSOCIATED SIGNS AND SYMPTOMS Symptom Number Female Male Total % TACO Events Dyspnoea % Increase in blood pressure % Pulmonary oedema % Chills / Rigors % Stridor / Wheeze % Fall in O2 saturation % Tachycardia % Chest pain % Restlessness / Anxiety % NZ BLOOD SERVICE ANNUAL HAEMOVIGILANCE REPORT

28 12. Transfusion Associated Circulatory Overload (TACO) continued Table 12.3 shows the number of TACO events reported each year for the period TABLE 12.3 ANNUAL NUMBER OF TACO EVENTS (IMPUTABILITY 3) Year Reported TACO Events Total Component Units Transfused Frequency Rate / 10,000 Units Transfused (95%CI) ,568 1:12, (4.6 to 14.1) ,919 1:7, (7.9 to 19.7) ,668 1:5, (12.3 to 26.4) ,995 1:8, (7.0 to 19.1) Total ,150 1:7, (10.0 to 15.7) 3% of all reported events were classified as TACO, however they were responsible for 17% of events graded with a severity score 2 (Table 12.4). TABLE 12.4 SEVERE TACO EVENTS (IMPUTABILITY 3) Grade 2 (Severe) Severity Grade Grade 3 (Life Threatening) Grade 4 (Death) All Adverse Events Number Total TACO Events Number Percentage of Grade 15% 24% 50% 17% TACO occurs predominantly in older recipients in whom careful consideration of total volume and rate of transfusion is particularly important along with judicious use of diuretics to avoid fluid overload. CASE C A 93 year old female rest-home resident weighing 71kg was admitted to a day-procedures ward for symptomatic anaemia with haemoglobin 78 g/l and no evidence of blood loss. Blood pressure 132/62 mmhg. Pulse oximetry SaO2 100%. She had a background medical history of essential hypertension, recurrent urinary tract infections, infrequent angina pectoris and mild leg oedema responsive to low-dose diuretic. Renal function as calculated by egfr was moderately reduced at 45 ml/min. Three units red cells were transfused uneventfully and the patient was discharged back to primary care the same day. Increment haemoglobin was 117 g/l. The patient s regular dose furosemide 40 mg had been withheld for the 48 hours prior and no interval diuretic was administered following the red cell transfusions. Approximately 8 hours later, the patient complained of dyspnoea and nausea. The rest-home staff documented BP 190/91 mmhg and SaO2 95% along with wheezy, laboured breathing and pitting oedema of the distal lower limbs. Upon transfer back to hospital approximately a further 11 hours later, the patient appeared jaundiced and cyanosed, was cold and clammy with BP 60/40 mmhg and SaO2 91% on 6L of supplemental oxygen. There was failure to respond to furosemide iv and dopamine infusion and the patient died later the same day. The rapid onset of congestive heart failure following blood transfusion were considered consistent with TACO and an imputability score of 4 (likely/probable) was assigned to this severe event. 26 NZ BLOOD SERVICE ANNUAL HAEMOVIGILANCE REPORT 2013

29 13. Transfusion-Associated Dyspnoea (TAD) DEFINITION Respiratory distress within 24 hours of transfusion that does not meet the criteria of TRALI, TACO, or allergic reaction and is not explained by the patient s underlying condition. During 2013, there were 26 events classified as TAD, 16 involving female recipients and 10 involving male recipients. The mean age was 63 years (range 4 96). Twenty two (84%) of the events were classified as non-severe (grade 1) and 4 (16%) were classified as severe with a severity score 2. Two of the events were classified as life threatening (grade 3). The clinical features are summarised in Table TABLE 13.1 TAD EVENTS (IMPUTABILITY 3) 2013 BY ASSOCIATED SIGNS AND SYMPTOMS Symptom Number Female Male Total % TAD Events Dyspnoea % Increase in blood pressure % Stridor / Wheeze % Chills / Rigors % Restlessness / Anxiety % Cough % Tachycardia % Fall in O2 saturation % Pulmonary oedema % Cough % Chest pain 1 1 4% NZ BLOOD SERVICE ANNUAL HAEMOVIGILANCE REPORT

30 13. Transfusion-Associated Dyspnoea (TAD) continued Table 13.2 shows the number of TAD events reported each year for the period TABLE 13.2 ANNUAL NUMBER OF TAD EVENTS (IMPUTABILITY 3) Year TAD Events Rate / 100,000 Total Component Frequency Units Transfused Units Transfused (95%CI) ,181 1:19, (2.4 to 10.2) ,587 1:12, (4.5 to 13.8) ,568 1:17, (2.8 to 10.9) ,919 1:25, (1.6 to 8.8) ,668 1:9, (5.9 to 6.7) ,995 1: (12.8 to 27.9) Total ,918 1:13, (5.7 to 9.3) Table 13.3 shows TAD events by recipient gender along with data on recipient age. TABLE 13.3 TAD EVENTS (IMPUTABILITY 3) 2013 BY RECIPIENT GENDER Number Age (Years) Mean Minimum Maximum Female Male All TRANSFUSION-ASSOCIATED DYSPNOEA SHADOW OR SUBSTANCE Only a minority of transfusion reactions are associated with respiratory features (TRRF) however these are some of the most serious transfusion-related adverse events (TRAE). Included in the TRRF group are transfusion-associated circulatory overload (TACO) and transfusion-related acute lung injury (TRALI). Allergic reactions, particularly of the more severe type, can also have respiratory features. Some TRRF do not neatly fit the ISBT definitions for TACO, TRALI or allergic reaction, in which case the ISBT recommends assigning the event to the separate category of transfusion-associated dyspnoea (TAD). Table 13.4 details TRRF for the period , the number of these events meeting criteria for more definitive pathophysiologic entities TACO and TRALI, as well as those categorised as TAD. 28 NZ BLOOD SERVICE ANNUAL HAEMOVIGILANCE REPORT 2013

31 13. Transfusion-Associated Dyspnoea (TAD) continued TABLE 13.4 ANNUAL NUMBER OF TRANSFUSION REACTIONS WITH RESPIRATORY FEATURES (IMPUTABILITY 3) BY EVENT TYPE Year All events No. TACO TRALI TAD TRRF as % As % As % As % As % As % As % of all of all of No. of all of No. of all of events events TRRF events TRRF events TRRF Data for 2006 & 2007 includes all reported events. From 2008 onwards, data shown is for events of imputability 3. 2 In 2007 some TAD events were included in the category Other. TAD events have been reviewed using additional information from clinical case notes in an attempt to re-classify as true pathophysiologic entities. Also of interest, was how the information in initial transfusion reaction reports compared with that in case notes, whether the number of cases classified as TAD has increased, and how NZBS Haemovigilance (HV) compares with other national HV systems with regard to TRRF classification. The results are summarised below. Thirty seven events, from 14 hospitals, classified as TAD between 1st June 2011 and 31st May 2013 were reviewed. Two independent reviewers examined the information for the 37 events and their corresponding clinical case notes and attempted re-classification using standard ISBT definitions. Patient age varied from 4 to 95 years. Twenty two events involved females and 15 involved males. In 31 / 37 TAD events RBC were the sole blood component involved; in 1 / 37 RBC plus FFP; in 2 / 37 platelets alone; in 1 / 37 platelets plus FFP; in 1 / 37 FFP alone; and in 1 / 37 cryodepleted plasma alone. All HV reports had information on heart rate, respiratory rate, and blood pressure. Additional clinical information relevant to the assessment of TRRF was sought in both the HV reports and from clinical case notes. Table 13.5 summarises these results. TABLE 13.5 INFORMATION SOURCE FOR REVIEW OF TAD EVENTS (IMPUTABILITY 3) Information source HV report Case notes Both Neither Chest X-ray or other chest imaging 7 (19%) 19 (51%) 7 (19%) 18 (49%) JVP or CVP 3 (8%) 15 (40%) 2 (5%) 21 (57%) BNP 4 (11%) 5 (13%) 3 (8%) 31 (88%) Fluid balance assessment 2 (5%) 6 (16%) 2 (5%) 31 (88%) NZ BLOOD SERVICE ANNUAL HAEMOVIGILANCE REPORT

32 13. Transfusion-Associated Dyspnoea (TAD) continued From review of the clinical case notes, for 17 (45.9%) events, the reporting clinician had either no diagnosis or did not consider the event to be transfusion-related. The diagnosis was TACO for 13 (35.1%) events, TAD for 3 (8%) events and for 4 (11%) the adverse event was not a TRRF. Results of re-classification by the reviewers are summarised in Table Intuitively, inter-rater agreement seems good but the statistic suggests this was only poor or moderate. Prevalence, prior knowledge effects, sample size and number of categories may be causes of the apparent paradox. TABLE 13.6 REVIEWED AND RE-CLASSIFIED TAD EVENTS (IMPUTABILITY 3) Original HV report Clinical case notes Review 1 Review 2 Review 1 Review 2 TAD Category TACO Other TRAE Not Tx-related / no reaction / no comment Kappa (95% CI) (-0.13 to -0.01) 0.4 (0.19 to 0.66) Inter-rater agreement worse than by chance alone moderate From this review a number of conclusions and comments can be made. TRRF are about 4-10% and TAD about 1-3.5% of all TRAE in NZBS HV. Roughly a third of all TRRF are classified as TAD. The year-to-year differences in the number of TRRF or TAD are likely to be insignificant. Reports of TAD and TRRF in other national HV systems are variable (data not shown) and there may be differences in the strictness with which ISBT definitions are applied. Review of HV reports resulted in re-classification in <10% of TAD events. However, using information from case notes, 57% / 59% of TAD events were re-classified by the two reviewers including 16% / 22% re-classified as TACO. Equally significant, in 40% / 43% the TAD classification did not change. No TAD event was re-classified as TRALI nor was TRALI diagnosed by the clinical team in any case. TRAE Other and not-transfusion-related constituted 8.1% / 2.7% and 27% / 40.5% of re-classifications. The information in HV reports is inadequate. Appropriate cases should be promptly followed up using a more detailed questionnaire or another mechanism. Events classified as TAD in NZBS HV appear appropriate as per standard ISBT definitions. A significant proportion of reported TRRF are misclassified (though not per standard definitions). Under-reporting of transfusion reactions, including TRRF, is well known. Many TACO go unrecognised and the diagnostic criteria for TACO as per ISBT definition may need to be refined and widened. Diagnostic criteria that are applicable to the non-acute care setting need to be developed. A points-based system using major and minor criteria may be useful. BNP measurements may be useful. Where appropriate, pre- and post-transfusion samples should be tested for BNP. A post-transfusion BNP 250 pg/ml or a pre-/post-transfusion BNP ratio of 1.5 may suggest a cause other than TACO. Whole blood BNP levels are relatively stable for 72 hours at 4 C potentially allowing BNP estimations in samples collected for other purposes. There are surprisingly few studies on TACO. A prospective study of TACO diagnosis based on history, symptoms and signs compared with diagnosis based on gold standard investigations such as echocardiography may be useful. BNP measurements may be more valuable in the diagnosis of heart failure than history, symptoms and clinical signs alone. Clear cut or exclusive clinical entities may not be present. Mild, atypical or overlap syndromes may occur. In the case of overlap syndromes, attempting to assign one designation may be futile or misleading. It is also possible that TRRF which are not TACO, TRALI or allergic, and whose mechanism is presently unknown, do occur. A prospective study of TRRF should be performed to get a better estimate of the incidence of the different entities that lead to this clinical presentation. Many doctors and nurses have poor understanding of transfusion reactions. Education of those involved in patient blood transfusion will likely benefit not only HV but also patient outcomes. 30 NZ BLOOD SERVICE ANNUAL HAEMOVIGILANCE REPORT 2013

33 14. Unclassifiable Complications of Transfusion (UCT) DEFINITION Occurrence of an adverse effect or reaction temporally related to transfusion, which cannot be classified according to an already defined event, with no risk factor other than transfusion. During 2013, there were 46 reports received of transfusion-related adverse events which could not be classified into a definitive category. Seventeen of these were excluded from the analysis on the basis that the event could be attributable to a cause other than the transfusion. The remaining 29 events included in the analysis involved 19 female and 10 male recipients. The predominant clinical features of these UCT events are summarised in Table TABLE 14.1 UCT EVENTS (IMPUTABILITY 3) 2013 BY ASSOCIATED SIGNS AND SYMPTOMS Symptom Number of Events Pain: chest (7),other (3) 10 Flushing 7 Arrhythmia 4 Other 3 Nausea 2 Hypoxaemia 1 Reaction to DMSO 1 Tonic-clonic seizure 1 Total 29 The types of blood components involved in UCT events are summarised in Table TABLE 14.2 UCT EVENTS (IMPUTABILITY 3) 2013 BY BLOOD COMPONENT TYPE Red Cells PAS Apheresis Platelets PAS Pooled Platelets Autologous Stem Cells Total NZ BLOOD SERVICE ANNUAL HAEMOVIGILANCE REPORT

34 15. Hypotensive Transfusion Reaction DEFINITION Decrease in systolic and/or diastolic blood pressure of >30 mmhg occurring during or within one hour of completing transfusion. All other categories of adverse reactions presenting with hypotension must have been excluded together with underlying conditions that could explain hypotension. During 2013, two reported events were classified as hypotensive transfusion reactions. Red cell units transfused were implicated in one reaction and platelet units in the other. Both patients were male and their ages were 56 and 84 years. The severity grade of one of the reactions was life threatening (grade 3) while the other was non-severe (grade 1). 16. Reports Involving Paediatric Patients During 2013, there were 30 events (6.9% of all events) involving recipients aged 15 years or younger. For this period, recipients of blood components aged 15 years or younger numbered 2,235 (6.8% of total). Allergic reactions were the most frequent adverse event reported in this age group (63%). Table 16.1 details the event type and severity of adverse events occurring in paediatric patients. TABLE ADVERSE EVENTS (IMPUTABILITY 3) 2013 IN RECIPENTS 15 YEARS AGE BY EVENT TYPE Event Type Number Percentage of Events Gender Severity Score Female Male 1 2 Allergic 19 63% FNHTR 4 13% IBCT 2 7% 2 2 UCT 2 7% Near Miss 1 3% 1 1 TACO 1 3% 1 1 TAD 1 3% 1 1 Total NZ BLOOD SERVICE ANNUAL HAEMOVIGILANCE REPORT 2013

35 17. Delayed Haemolytic / Serologic Transfusion Reactions (DHTR / DSTR) DEFINITION A delayed haemolytic transfusion reaction is one in which symptoms and clinical or laboratory signs of increased red cell destruction occur between 24 hours and 28 days following the transfusion of blood or a blood component. If markers of increased red cell destruction are unavailable or not supportive of a haemolytic process, the event is classified as a delayed serological transfusion reaction. These events are normally identified by the blood bank when repeat testing identifies a new blood group antibody and a positive DAT in a patient recently transfused. Haemolysis is suggested by a poor post-transfusion haemoglobin increment, clinical jaundice or a raised serum bilirubin, raised LDH and low/undetectable serum haptoglobin levels. During 2013, there were two reports of DHTR and 12 reports of DSTR of imputability 3. Table 17.1 shows these events by recipient gender along with data on recipient age. Table 17.2 details the specificities of the blood group antibodies implicated in the DHTR and DSTR events. Antibodies to the Kidd blood group antigens accounted for 50% of the antibodies identified in the delayed transfusion reactions. TABLE 17.1 DELAYED TRANSFUSION REACTIONS (IMPUTABILITY 3) 2013 BY EVENT TYPE AND RECIPIENT GENDER Number Age (years) Mean Minimum Maximum DHTR DHTR Female 0 0 Male Female DSTR NZ BLOOD SERVICE ANNUAL HAEMOVIGILANCE REPORT

36 17. Delayed Haemolytic / Serologic Transfusion Reactions (DHTR / DSTR) continued TABLE 17.2 DELAYED TRANSFUSION REACTIONS (IMPUTABILITY 3) 2013 BY SPECIFICITY OF RED CELL ANTIBODY Antibody Specificity Number Delayed Haemolytic Transfusion Reaction C+e+Jk b 1 Jk 3 1 Jk a 3 K 2 Jk b 1 M 1 Delayed Serological Transfusion Reaction Fy b 1 E 1 E+S 1 e 1 Fy a +Jk b 1 CASE D A 60 year old male had a positive red cell antibody screen (RCAS) with anti-c+e identified in February Subsequent RCAS were negative on several occasions between September 2011 and April 2013 including on admission to an Emergency Department with acute GI bleeding and haemoglobin of 51 g/l. A request was made for four units of emergency red cells. Units compatible for the historic antibody were not available and Transfusion Medicine Specialist approval was given for the issue and transfusion of three units of group O RhD negative and one unit of group O RhD positive red cells. Nine days following the transfusion the patient s direct antiglobulin test (DAT) was positive for IgG and C3d, with anti- C+e+Jk b identified in the patient s plasma and in an eluate from the patient s red cells. The serum bilirubin had increased from 10 μmol/l pre-transfusion to 53 μmol/l nine days post-transfusion, the LDH had increased from 273U/L to 1542U/L and the haptoglobin was 0.2g/L. The imputability score was classified as certain and the severity grade as 1 (non-severe). CASE E A 41 year old male admitted with a shot gun wound to the leg with acute bleeding. The patient was transfused with 13 units of un-crossmatched emergency red cell units before pre-transfusion testing was completed. Also transfused were eight units of fresh frozen plasma, six units of cryoprecipitate and one unit of platelets. Anti-Jk 3 was identified in the patients plasma, all the red cells units were Jk 3 positive. Anti-Jk 3 reacts with red cells whenever a Jk a or Jk b antigen is present but not with Jk(a-b-) red cells. The Jk(a-b-) phenotype is rare in Caucasians but the phenotype is more common in New Zealand Polynesians, 0.9%. Four Jk(a-b-) red cell units were sent to the hospital, two Jk(a-b-) from the current national red cell inventory and two thawed after storage in liquid nitrogen. Six days following the transfusion of the 13 incompatible red cell units the DAT was positive for IgG with anti-jk 3 eluted. The haemoglobin fell from 86 g/l two days post-surgery to 67 g/l on day six with no post-operative bleeding. The serum bilirubin had increased from 8 μmol/l pre-transfusion to 19 μmol/l. The LDH was 450 IU/L and the haptoglobin was <0.2 g/l. The imputability score was classified as certain and the severity grade as 1 (non-severe). 34 NZ BLOOD SERVICE ANNUAL HAEMOVIGILANCE REPORT 2013

37 18. Adverse Events Associated with Fractionated Plasma Products Adverse events associated with fractionated plasma products have a separate reporting procedure from those associated with fresh blood components (Appendix II). Events of any imputability are reported to the manufacturer, CSL Behring (Australia) Pty Ltd, and periodic reports are provided to the Centre for Adverse Reaction Monitoring (CARM). During 2013, 42 adverse events associated with fractionated plasma products were reported. Of the 42 events, 38 involved adverse reactions and the remaining 4 reports involved administration of an incorrect product or dose. The events associated with an incorrect product or dose are described in chapter 19: Incorrect Blood Components Transfused (IBCT). All but two of the adverse events were classified as non-severe. The exceptions were two events associated with the infusion of Intragam P and Prothrombinex -VF. Both reports were classified with an imputability of likely/probable. CASE F. SEVERE EVENT INVOLVING PROTHROMBINEX -VF A male patient on warfarin anticoagulant therapy presented to the Emergency Department with an INR >9 and groin pain due to retroperitoneal bleeding. He was charted 5 vials of Prothrombinex -VF but complained of feeling different within 5 minutes of the infusion starting and then developed severe chest pain and shortness of breath with extreme pallor. He was given GTN spray and subsequently developed a fall in systolic blood pressure to 64 mmhg which improved with crystalloid infusion to a systolic BP > 100 mmhg. The pain resolved after 10 minutes but recurred 20 min later. Morphine was given and he was transferred to ICU. Troponin levels were found to have increased. The patient was later treated with 2 units of FFP. Follow-up information indicated that only approx. 3 ml of Prothrombinex -VF was infused. CASE G. SEVERE EVENT INVOLVING INTRAGAM P A male patient with plasma cell myeloma, dialysis-dependent chronic renal impairment and acquired hypogammaglobulinaemia was commenced on Intragam P. The initial infusion was commenced rapidly with 200mL given over 10 minutes, followed by the next 50mL over 5 minutes. The patient developed acute shortness of breath, chest pain and was flushed and restless. The infusion was stopped immediately and oxygen administered together with Paracetamol. The patient had recovered approximately one hour later. Table 18.1 shows the 42 adverse events by fractionated plasma product type. Additional information on events associated specifically with administration of Intragam P is provided in Table TABLE 18.1 TRANSFUSION-RELATED ADVERSE EVENTS (ANY IMPUTABILITY) 2013 ASSOCIATED WITH FRACTIONATED PLASMA PRODUCTS Product Type Event Type Number of Reports Intragam P Various, see Table Prothrombinex -VF Allergic, myocardial ischemia, thrombotic 3 Albumex 20 Febrile 2 RhD Immunoglobulin-VF Expired product, incorrect dose 2 Albumex 4 Allergic 1 Hepatitis B Immunoglobulin-VF Incorrect dose 1 Privigen (IV Immunoglobulin) Pain, nausea and lethargy 1 Tetanus Immunoglobulin-VF Near miss event 1 Total 42 NZ BLOOD SERVICE ANNUAL HAEMOVIGILANCE REPORT

38 18. Adverse Events Associated with Fractionated Plasma Products continued TABLE 18.2 TRANSFUSION-RELATED ADVERSE EVENTS (ANY IMPUTABILITY) 2013 ASSOCIATED WITH INTRAGAM P Imputability Severity Type of Reaction Total Unlikely Possible Likely / Probable Highly probable Nonsevere Severe Pain* Allergic Febrile Haemolytic Bursitis Muscle ache* Periorbital oedema Breakthrough varicella infection Shortness of breath & chest pain Total *Pain Associated with the Administration of Intragam P In September 2013 NZBS was notified of a number of adverse reactions involving one batch of Intragam P. The events occurred in a range of patients and included those with immunodeficiency and neurological indications for immunoglobulin therapy. The main symptoms were severe muscle pain in the thighs, limbs, buttocks and/or abdomen. The symptoms commenced shortly after completing the infusions and lasted for up to 48 hours, in some cases requiring pain relief. Several patients had been receiving Intragam P for extended periods and had not previously experienced similar symptoms. The implicated batch of Intragam P was used for the treatment of a number of patients only in one area of New Zealand. Medsafe, responsible for the regulation of therapeutic products in New Zealand, was informed and the implicated batch recalled from circulation. The manufacturer, CSL Behring (Australia) Pty Ltd, was informed and an investigation to establish the likely cause was undertaken. 36 NZ BLOOD SERVICE ANNUAL HAEMOVIGILANCE REPORT 2013

39 19. Incorrect Blood Component Transfused (IBCT) DEFINITION IBCT is the transfusion of a blood component or product that was intended for another patient or one that did not meet the patient s requirements. During 2013, there were 25 IBCT events reported (Table 19.1). This compares to 19 IBCT events reported in TABLE 19.1 IBCT EVENTS 2013 IBCT Event Type of Product Incorrect product/ dose Red Cells (5) RhD Immunoglobulin- VF (4) Fresh Frozen Plasma (3) Prothrombinex -VF (1) Hepatitis B Immunoglobulin-VF (1) Non-irradiated components transfused Red Cells (4) Platelets (1) Inappropriate transfusion RhD Immunoglobulin- VF (5) Other Red cells (1) Description Red cells requested and issued when patient required platelets. Red cell transfused. Nursing staff failed to recognise difference between red cells and platelets. Three emergency group O RhD negative red cell units issued. Retrospective compatibility tests identified anti-fya in patient and all three units transfused as Fya positive. No adverse reaction in patient. One emergency group O RhD negative red cell unit issued to a patient known to have anti-fya. Transfusion Medicine Specialist authorised release of emergency unit. No adverse reaction in patient. Baby, 8 kg, not actively bleeding, prescribed a transfusion of 200mL red cells yet received 135mL. Two units fresh frozen plasma transfused when two units of platelets prescribed. Nurse requested fresh frozen plasma instead of the prescribed platelets. Plasma units transfused. Unit of fresh frozen plasma thawed and issued to clinical unit. Returned >30 minutes after issue. Returned to 4 C storage, issued and transfused 19 hours later. Component should have been discarded after uncontrolled storage >30 minutes. Red cells requested and issued when patient required platelets. Red cells transfused. Nursing staff failed to recognise difference between red cells and platelets. Unit of fresh frozen plasma thawed, expiry date not changed post thawing. Site of Error Clinical Clinical Clinical Laboratory Clinical Laboratory Incorrect dose of RhD Immunoglobulin-VF issued and administered. (2 Laboratory events) Vial of RhD Immunoglobulin-VF issued and administered two weeks post Laboratory expiry of the product. Incorrect dose of Hepatitis B Immunoglobulin-VF given to baby, 400IU dose Laboratory issued and administered instead of 110 IU dose. Fresh frozen plasma and Prothrombinex -VF labelled with incorrect patient Laboratory name and administered to patient with a different name. Event involved two trauma patients within Emergency Department. Clinical Blood bank not informed of requirement for irradiated components, nonirradiated red cells and platelets issued and transfused. (2 Clinical events) Patient required irradiated components, non-irradiated red cells issued and transfused. (3 events) RhD Immunoglobulin-VF issued and administered to RhD negative patient previously sensitised to RhD. (3 events) RhD Immunoglobulin-VF administered to RhD positive woman. Laboratory Laboratory Clinical RhD Immunoglobulin-VF given to RhD negative woman following delivery of Laboratory RhD negative baby. Blood bank received a two unit red cell request with incorrect patient birth date given. The error, detected and corrected in clinical area prior to receipt Clinical of the units, was not conveyed to blood bank. Following one unit being transfused, the incongruency prompted return of the second unit. NZ BLOOD SERVICE ANNUAL HAEMOVIGILANCE REPORT

40 20. Near Miss Events DEFINITION A near miss event is an error or deviation from standard procedure or policy that is discovered before the transfusion and that, if not discovered, would have led to an inappropriate transfusion and has potential for an adverse reaction in the recipient. Near miss events are usually reported to a local incident management system (within a DHB) so that appropriate investigations are undertaken and the necessary education and preventive actions are implemented. During 2013, there were 11 near miss events formally reported to the Haemovigilance Programme, 9 involving wrong blood in tube (WBIT) events. A further 27 near miss events were identified from the NZBS incident management system. These events are summarised in Table TABLE 20.1 NEAR MISS EVENTS 2013 BY ERROR TYPE AND SITE Error Site of Error Blood Bank Processing Clinical Total Wrong product/component issued (including wrong dose or wrong patient) RBC 3 FFP RhD immunoglobulin 1 Other blood products 5 Irradiation errors Labelling errors Expiry of blood components 3 3 Other 2 2 WBIT (reported by DHB Blood Bank) 9 9 Total NZ BLOOD SERVICE ANNUAL HAEMOVIGILANCE REPORT 2013

41 21. NZBS Wrong Blood in Tube (WBIT) Events A wrong blood in tube, sometimes referred as wrong name on tube, error is when the pre-transfusion sample was collected from the wrong patient or the sample was labelled with the details of another patient. These types of errors are normally identified when ABO and RhD testing shows a different blood group from the historic results for the patient in e-progesa. A current WBIT is where the sample received is proven to be incorrectly labelled. A historic WBIT is where the historic grouping result was likely based on a sampling or labelling error. Silent errors can occur when the wrong patient is bled but where the two patients have the same ABO and RhD groups. The corrected WBIT rate is calculated using the following equation: Corrected WBIT rate = Number of historical groups Number of WBIT x 1.6 The correction factor 1.6 is based on New Zealand blood group frequencies and corrects reported rates to take into account silent WBIT events. Rather than relying on voluntary Haemovigilance reporting of near miss events, the NZBS incident management system collects accurate WBIT data from the six NZBS Blood Banks. In 2013, historic ABO RhD blood groups were available in e-progesa for 64.3% of all pre-transfusion samples submitted to NZBS Blood Banks. There were 13 WBIT errors identified. In four cases, the historic result was assumed to be incorrect. Table 21.1 shows the corrected WBIT rate for the 9 current WBIT events reported by the NZBS Blood Banks in The overall corrected WBIT rate was 1.6 per 10,000 samples (1:6,232). TABLE 21.1 NZBS WBIT EVENTS 2013 BY BLOOD BANK SITE WBIT Events Historic Groups Rate / 10,000 WBIT Specimens Frequency 1 (95% CI) 1 Wellington 3 14,155 1:2, (1.2 to 8.3) Auckland 4 31,258 1:4, (0.9 to 4.5) Waikato 2 19,069 1:5, (0.4 to 5.0) Christchurch 0 13,454 0 Dunedin 0 6,160 0 Palmerston North 0 5,639 0 NZBS Total 9 89,735 1:6, (0.9 to 2.7) 1 Corrected to account for silent errors. NZ BLOOD SERVICE ANNUAL HAEMOVIGILANCE REPORT

42 21. NZBS Wrong Blood in Tube (WBIT) Events continued Table 21.2 shows the cumulative number of WBIT errors for the six NZBS Blood Banks over a seven year period from The overall corrected WBIT rate was 2.6 per 10,000 samples (1:3,782). An international study (Dzik et al. Vox Sanguinis 2003: 85; 40-47) involving 10 countries reported an approximate median WBIT rate of 5 per 10,000 samples (1:2,000). TABLE 21.2 NZBS WBIT EVENTS BY BLOOD BANK SITE WBIT Events Historic Groups Rate / 10,000 WBIT Specimens Frequency 1 (95% CI) 1 Wellington 31 87,541 1:1, (4.3 to 7.5) Palmerston North 7 39,745 1:3, (1.5 to 5.1) Auckland ,098 1:4, (1.9 to 3.2) Waikato ,968 1:5, (1.3 to 3.0) Dunedin 5 42,833 1:5, (0.9 to 3.8) Christchurch ,920 1:6, (0.9 to 2.5) NZBS Total ,105 1:3, (2.3 to 3.1) 1 Corrected to account for silent errors. The annual NZBS WBIT event rate per 10,000 samples from is shown in Figure FIGURE 21.1 ANNUAL NZBS WBIT EVENT RATE Upper/Lower 95%CI WBIT Rates / 10,000 Samples Rate / 10,000 Samples Year 40 NZ BLOOD SERVICE ANNUAL HAEMOVIGILANCE REPORT 2013

43 22. Bacterial Monitoring of Platelet Concentrates Bacterial contamination in platelets can result in sepsis with the associated morbidity occasionally leading to death and as such continues to be a serious risk of transfusion. Bacteria will either enter the component at the time of venepuncture or more rarely this occurs due to an occult infection in the donor but can also enter due to a breach of the closed system during processing. The warm storage temperature of 22 ± 2 C combined with the platelet component itself is an ideal medium for some, though not all, bacteria to flourish. The likelihood of detecting bacteria in platelet components and the consequent risk of clinical sepsis in the recipient increases with the cumulative age of the platelet. International Haemovigilance programmes report the rate of septic reactions to bacterially contaminated platelets as % (1 in 100,000 1 in 50,000) and the risk of death from a contaminated platelet as % (1 in 500,000 1 in 250,000). The Serious Hazards of Transfusion (SHOT: the UK Haemovigilance system) 2009 report identified approximately 1 septic reaction per 75,000 platelets issued and 1 death per 273,000 platelets issued. Similar data has been reported by both the USA and French Haemovigilance where septic reactions are 1 in 83,000 and 1 in 50,000 respectively. The rate of fatal reactions reported by the USA is approximately 1 in 500,000 while France reports 1 in 300,000. Data from the NZBS Haemovigilance scheme is consistent with these data. During the period two reports were received by the Haemovigilance Office that met the criteria utilised by the SHOT scheme. In the same period over 100,000 platelet components were issued to hospitals. One of the two implicated platelet components had been cultured as part of the current monitoring scheme used by NZBS. Blood service organisations, including NZBS have introduced initiatives aimed at reducing the incidence of bacterial contamination in blood components including improved skin disinfection at the venepuncture site and diversion of the first 30-50mL of the donation in order to avoid skin commensals contaminating the donation. These measures are widely accepted to reduce the risk of contamination by 60-70%. Increasing concern relating to bacterial transmission of platelet concentrates has led a number of Blood Services to investigate methods to further reduce the risk. Canada, the Netherlands and Hong Kong were the first countries to introduce a formal requirement for the use of pre-release bacterial detection systems for platelet concentrates. In recent years many other countries have followed. In particular the AABB introduced a formal requirement for screening of platelet components in 2004 and have required testing to utilise either FDA approved systems or systems shown to have equivalent sensitivity since The Australian Red Cross Blood Service (ARCBS) implemented a pre-release culture system across its sites in April This involves culture on day one post-production with no quarantine of cultured platelets. A number of systems are currently available to support bacterial detection in platelet concentrates. These can either be used to monitor the level of contamination, as required by the Council of Europe Guide, or to support release of platelets on a negative at release basis. NZBS commenced a pilot study to assess the frequency of bacterial contamination during October The scheme has been progressively rolled out such that by the end of 2007 all sites within NZBS that manufacture platelets were participating. The proportion of components tested increased significantly during 2013 such that approximately 92% of all apheresis collections and platelet pools were cultured. Apheresis collections are normally split into two components (doses) soon after production. Currently only one of the 2 components is tested. The detailed results of day 2 culture testing undertaken by individual sites during 2013 is shown in Table 22.1 TABLE 22.1 PROPORTION OF DAY 2 PLATELET COMPONENTS CULTURED 2013 BY PROCESSING SITE Apheresis Platelets Pooled Platelets Site Collections Components Tested % Tested Produced Components Tested % Tested Auckland 1,831 1, ,899 3, Waikato ,905 1, Wellington ,701 1, Christchurch ,388 1, Manawatu Otago Total 4,846 4, ,893 8, NZ BLOOD SERVICE ANNUAL HAEMOVIGILANCE REPORT

44 22. Bacterial Monitoring of Platelet Concentrates continued The NZBS protocol for bacterial monitoring involves testing of platelets at day 2 of storage. A 6ml sample of the concentrate is used to inoculate an aerobic BacT/ALERT culture bottle. The bottles are cultured until a positive signal is obtained or until the platelet concentrate has expired. The platelets are available for release immediately following sampling and will be withdrawn from inventory in the event that a positive culture signal is obtained. Results of testing undertaken during 2013 are shown in Table 22.2 TABLE 22.2 RESULTS OF CULTURING DAY 2 PLATELET COMPONENTS 2013 National All reactives National Confirmed reactives Total Components Sampled Number Reactive % Reactive Frequency of Reactives 12, :978 12, :4237 The data indicates that NZBS systems compare well with published data. The contamination rate of platelets identified using the BacT/ALERT culture system is reported to be between % (1 in 5,000 3 in 1,000). There is increasing data that demonstrates that bacterial culture of samples collected at day one of storage reduces but does not eliminate the risk of subsequent bacterial growth in platelet concentrates. Data from Ireland and the American Red Cross published during 2007 indicates that this testing might only detect 50% of contaminated platelet concentrates. This view is supported by the results of day 8 testing of expired platelet components undertaken by NZBS. Data for 2013 is shown in Table A review of data for the 5 year period identified that 15 of 15,383 day 8 components cultured were reactive (0.1%) with 6 being confirmed (0.03%). TABLE 22.3 RESULTS OF CULTURING OUT-OF-DATE PLATELET COMPONENTS 2013 National All reactives National Confirmed reactives Total Components Sampled Number Reactive % Reactive Frequency of Reactives 2, :777 2, :777 NZBS is currently developing systems to support 100% culture of platelet components in order to bring us in line with international practice. This will be achieved by extending the platelet shelf-life to 7 days and therefore will not lead to any increased risk of expiry. Testing will be extended to include the use of both aerobic and anaerobic culture bottles with an increased sample volume. This will improve system sensitivity and reduce any additional risk associated with the longer shelf life. This approach will mirror that currently in place in the United Kingdom and is similar to an approach being proposed by the Australian Red Cross Blood Service. A proposal has been submitted to Medsafe to allow this to proceed. Preliminary approval has been obtained and further data is being compiled to allow final approval with the aim of implementation, if approval granted, in early NZ BLOOD SERVICE ANNUAL HAEMOVIGILANCE REPORT 2013

45 23. Donor Infectious Disease Screening and Transfusion Transmitted Infections (TTI) In New Zealand, all blood donations are screened for hepatitis B surface antigen (HBsAg), HBV DNA, anti-hcv, HCV RNA, anti-hiv-1 & -2, HIV RNA and syphilis EIA. All new donors are also tested for anti-htlv-i & -II. Additional testing is performed on selected donations e.g., CMV IgG for fetal and neonatal transfusions. Trypanasoma cruzi (Chagas), and malarial antibody tests in donors who may pose a risk due to residence and/or travel to affected areas. During 2013, 160,211 donations were collected from 80,978 donors. 88% of the donors were repeat donors and 12% previously untested new donors. Table 23.1 shows the number of donors with confirmed positive serology in There were 21 donors confirmed positive for HBV and 5 confirmed positive for HCV. No HIV confirmed positive donors were identified during the year. TABLE 23.1 DONORS WITH CONFIRMED POSITIVE INFECTIOUS DISEASE SEROLOGY 2013 HBV HCV HIV Syphilis HBV Occult HTLV I/II Number New Donors (n=9,371) Repeat Donors (n=71,607) Total Donors (n=80,978) Rate per 100,000 Donations New Donors Repeat Donors All Donations New Donors 1:446 1:1,874 1:1,562 Frequency of Positive Donors Repeat Donors 1:23,869 Overall Frequency 1:3,856 1:16,196 1:13,496 1:26,993 NZ BLOOD SERVICE ANNUAL HAEMOVIGILANCE REPORT

46 23. Donor Infectious Disease Screening and Transfusion Transmitted Infections (TTI) continued Figure 23.1 shows the number of confirmed positive results each year over the period This shows a consistent reduction in detection rates for each of the main markers. Occult hepatitis B infection is defined as the presence of HBV DNA in donor plasma without detectable HBsAg outside the window period. Detection of these donors only became possible following the implementation of HBV DNA testing in FIGURE 23.1 ANNUAL NUMBER OF DONORS WITH CONFIRMED POSITIVE INFECTIOUS DISEASE SEROLOGY HBsAg pos anti-hcv pos Occult HBV anti-hiv pos 100 Total Number of Confirmed Positives Year NZBS was notified of three possible hepatitis B TTIs. Lookback investigations were undertaken to determine whether the patients might have acquired their hepatitis B infections by blood transfusion. The investigations are summarised overleaf. 44 NZ BLOOD SERVICE ANNUAL HAEMOVIGILANCE REPORT 2013

47 23. Donor Infectious Disease Screening and Transfusion Transmitted Infections (TTI) continued CASE H Patient A was noted to display a chronic infection profile serologically for hepatitis B. He had been extensively transfused following an internal injury. No pre-transfusion hepatitis B serology results were available. The transfusion record of Patient A identified that he had received 52 blood components from 67 donations. The increased number of donations relative to blood components transfused reflects the use of five platelet pools (each from five donors). NZBS reviewed the records for the donations contributing to the components transfused to Patient A. The review confirmed that all donations tested negative for both hepatitis B surface antigen and HBV DNA (Ultrio Plus). Retention samples were retrieved and retested. Repeat HBV DNA testing was undertaken on 64 of the donations with negative results. Retention samples were insufficient for HBV DNA testing of the other three. All of these three donors were found to be HBV DNA non-reactive either on subsequent donations or on an additional blood sample taken as part of the investigation. 66 of the 67 implicated donations were hepatitis B core antibody (anti-hbc) negative. The remaining donor was anti-hbc reactive at low level. Testing on a subsequent donation from the same donor gave a negative result in the anti-hbc assay suggesting that the initial result was likely a false positive one. Anti-HBs was present in 22 of the 67 donations. Additional samples were obtained, where possible, from all the donors. 43 of the 67 donors donated again following the implicated donation. Letters were sent to the remaining 24 donors and 18 of these gave a further sample for testing. The additional testing did not identify any untoward results with all samples being negative for anti-hbc and HBV DNA. A comment has been made on the records of the six donors that have not been retested to ensure further testing will occur in the event that they re-donate in the future. None of the 61 donors that were retested showed any evidence of seroconversion and in particular anti-hbc was absent in all cases. A possible source of transfusion associated hepatitis B is occult hepatitis B infection. These donors typically show a high titre anti-hbc result with low or absent anti-hbs. This pattern was not evident in any of the 67 donors implicated in the transfusions to Patient A. Unfortunately NZBS was unable to obtain additional samples on the remaining six donors. Three of these six donors were immune to hepatitis B as demonstrated by the presence of anti-hbs and could likely be excluded as the possible source of infection. The investigation failed to demonstrate any evidence that Patient A may have contracted hepatitis B infection as a consequence of the transfusions he received. Based on the results it was highly unlikely that the hepatitis B infection in Patient A arose as a consequence of the transfusion. NZ BLOOD SERVICE ANNUAL HAEMOVIGILANCE REPORT

48 23. Donor Infectious Disease Screening and Transfusion Transmitted Infections (TTI) continued CASE I Patient B developed jaundice and serological investigations were consistent with recent hepatitis B infection. As patient B had received a blood transfusion several months previously, NZBS received a lookback request. Testing of a pre-transfusion sample from Patient B was HBsAg and anti-hbc negative. The transfusion record of Patient B identified that he was transfused with two units of red cells. NZBS reviewed the records for the donations transfused to Patient B. This review confirmed that both donations tested negative for both HBsAg and HBV DNA (Ultrio Plus). One donor (Donor 1) made a subsequent donation three months later. The second donor (Donor 2) had not made a further donation but the donor was contacted and a further sample obtained for retesting. All retention samples were retrieved and retested and the new sample from Donor 2 was tested. The results are summarised below. Donor 1 Donor 2 Donation Date HBsAg Anti-HBs Anti-HBc NZBS HBV DNA Ref Lab HBV DNA September Negative Negative Negative Non-Reactive Non-Reactive December Negative Negative Negative Non-Reactive Non-Reactive September Negative Negative Positive Non-Reactive Non-Reactive February Negative Negative Positive Non-Reactive* Non-Reactive * Tested three times Transfusion transmitted hepatitis B can arise in two ways. Firstly as a consequence of an acute infection in the donor that is not detectable at the time of the original donation. When this occurs the donor will show evidence of seroconversion to hepatitis B markers on subsequent testing. Neither of the two donors shows any evidence of seroconversion. This route of transmission was therefore excluded. The second possible source of transfusion associated hepatitis B is occult hepatitis B infection. This normally involves a donor whose only markers of infection are hepatitis B core antibody and variable levels of HBV DNA. Hepatitis B surface antibody is typically low or absent. The results seen in donor 2 are consistent with this pattern but testing for evidence of HBV DNA (repeated three times on the second sample) were consistently negative. The clinical picture of acute hepatitis B evident in Patient B within four months of a transfusion and the pattern of results seen in donor 2 are consistent with a transfusion acquired infection. The repeated absence of detectable HBV DNA in either of the samples from Donor 2 tested means that it is not possible to confirm that transfusion is the cause of the infection. As a precautionary measure Donor 2 was removed from the donor panel and a lookback of recipients of the previous donations given by the donor was undertaken. CASE J A whole blood donor who had made 11 previous donations, all HbsAg and HBV DNA negative, was found to be HBV DNA (Ultrio Plus) reactive, Ultrio Discriminatory non-reactive, four months after their last donation. HBV DNA HBV DNA HBsAg Anti-HBs Anti-HBc Ultrio Plus Discriminatory Test Negative 0.49IU/L Reactive Reactive* Non-reactive* * Tested two times Five recipients of components prepared from previous donations given by the donor were identified and the responsible clinician notified with a recommendation that the recipients should be tested for evidence of hepatitis B. NZBS was subsequently informed that one of the five recipients had been diagnosed with chronic active hepatitis. Investigations demonstrated the presence of an abnormal, mutant form of hepatitis B infection. NZBS retains samples from all donations for a period of five years. Repeat HBV testing of the retention sample from this donation, including the HBV DNA test, were all negative. The history and time course is suggestive of a transfusion transmitted infection but unfortunately it has not been possible to obtain further samples from either the donor or the patient to confirm this. 46 NZ BLOOD SERVICE ANNUAL HAEMOVIGILANCE REPORT 2013

49 24. Adverse Events Associated with Blood Donation Adverse events associated with blood donation can occur during or after collection of the donation. Delayed complications are defined as a complication which has occurred after the donor has left the donation site. Delayed complications are notified either by a telephone call, personal visit, or letter. NZBS utilises definitions for these adverse events contained in the Standard for Surveillance of Complications Related to Blood Donation (2008) developed by the International Society of Blood Transfusion Working Party on Haemovigilance (Appendix III). A standardised national form is used by all collection sites to record the information for each donor adverse event (Appendix IV). The yearly reported donation-related adverse event rate per 10,000 donations continues to increase (Figure 24.1) and likely reflects on-going efforts within NZBS to improve consistency of reporting across the sites. FIGURE 24.1 ANNUAL DONATION-RELATED ADVERSE EVENT RATE PER 10,000 DONATIONS Event Rate / 10,000 Donations Year NZ BLOOD SERVICE ANNUAL HAEMOVIGILANCE REPORT

50 24. Adverse Events Associated with Blood Donation continued In New Zealand during 2013, 160,211 donations (125,684 whole blood, 29,585 plasmapheresis and 4,942 plateletpheresis donations) were collected. Adverse events were reported in relation to 4,483 of the donations, involving 4064 donors. The overall frequency of reported donation-related adverse events was 1:36. Adverse events are more frequently reported with apheresis procedures, particularly plateletpheresis, than whole blood donations (Table 24.1). TABLE 24.1 DONATION-RELATED ADVERSE EVENTS 2013 BY COLLECTION METHOD Procedure Donors Donations with Events Total Donations Frequency Rate / 10,000 Donations (95%CI) Whole blood donation 2,927 2, ,684 1: (224.7 to 241.4) Plasmapheresis ,585 1: (215.6 to 250.0) Plateletpheresis ,942 1: (833.4 to 994.0) All apheresis procedures 1,137 1,486 34,527 1: (311.0 to 348.7) Total procedures 4,064 4, ,211 1: (246.1 to 261.5) A number of donors experienced more than one adverse event with a single donation so in total there were 4,877 reported events; 3,083 involving whole blood donations and 1,794 with apheresis procedures. Immediate vasovagal reactions and bruising/haematoma were the most common events associated with donation. For whole blood donation the most common event (61.5%) was an immediate vasovagal reaction. For apheresis procedures, the most common event (65.7%) was bruising/haematoma. Donation-related adverse events by reaction type and collection method are shown in Table 24.2 and Table TABLE 24.2 DONATION-RELATED ADVERSE EVENTS 2013 BY REACTION TYPE Reaction All Blood Donations (Total Collections = 160,211) Number Events 1 Percentage Frequency Rate / 10,000 Donations (95% CI) Immediate Vasovagal 2, % 1: (122 to 133) Haematoma 1, % 1: (81 to 90) Painful Arm % 1: (10 to 14) Nerve irritation % 1:1,586 6 (5 to 8) Delayed Vasovagal % 1:1,652 6 (5 to 7) Other % 1:2,,762 4 (3 to 5) Delayed Bleeding % 1:6,162 2 (1 to 2) Nerve Injury % 1:10,681 1 (1 to 2) Allergy % 1:1, (0 to 1) Arterial Puncture 7 0.2% 1:22,887 0 (0 to 1) Tendon Injury 4 0.1% 1:40,053 0 (0 to 1) Total 3,928 1: (234 to 249) 1 Apheresis specific complications excluded, i.e., citrate reactions and red cell return failures. 48 NZ BLOOD SERVICE ANNUAL HAEMOVIGILANCE REPORT 2013

51 24. Adverse Events Associated with Blood Donation continued TABLE 24.3 DONATION-RELATED ADVERSE EVENTS 2013 BY REACTION TYPE AND COLLECTION METHOD Type Of Blood Donation Reaction Immediate Vasovagal Events Whole Blood (Total Collections = 125,684) % All Events Freq. 1, % 1:66 Haematoma % 1:154 Painful Arm % 1:990 Delayed Vasovagal % 1:1,396 Nerve Irritation % 1:1,795 Other %` 1:1,396 Delayed Bleeding % 1:6,615 Nerve Injury % 1:8,977 Allergy 7 0.2% 1:17,955 Arterial Puncture 7 0.2% 1:17,955 Tendon Injury % 1:125,684 Total :41 Rate / 10,000 Donations (95% CI) 151 (144 to 158) 65 (61 to 70) 10 (8 to 12) 7 (6 to 9) 6 (4 to 7) 7 (6 to 9) 2 (1 to 2) 1 (1 to 2) 1 (0 to 1) 1 (0 to 1) 0 (0 to 0) 245 (237 to 254) Apheresis (Total Collections = 34,527) Events 1 % All Events Freq % 1: % 1: % 1: % 1:4, % 1:1, % 1:1, % 1:4, % 1:3, % 1:11, % 1: :41 Rate / 10,000 Donations (95% CI) 43 (36 to 50) 161 (148 to 175) 19 (15 to 24)) 2 (1 to 4) 9 (6 to 13) 7 (5 to 10) 2 (1 to 4) 0 (0 to 2) 1 (0 to 3) 1 (0 to 3) 245 (229 to 262) Apheresis only Complications Events % Reaction Freq. Citrate Reaction % 1:63 RBC not returned % 1:87 Total Apheresis Specific Events 949 1:36 Rate / 10,000 Donations (95% CI) 159 (147 to 173) 116 (105 to 127) 275 (258 to 293) NZ BLOOD SERVICE ANNUAL HAEMOVIGILANCE REPORT

52 24. Adverse Events Associated with Blood Donation continued Table 24.4 and Table 24.5 detail the type, severity score and rate of adverse events per 10,000 donations. The majority of adverse events were classified as mild. In 2013, of the total 3,928 reported events, 860 were classified as moderate and only one, involving a whole blood donation, was classified as severe. No deaths were reported as a result of blood donation. Severe complications are defined as events resulting in any of the following: Hospitalisation: if it was attributable to the complication. Intervention: if required to preclude permanent damage or impairment of a body function or to prevent death (i.e., lifethreatening event). Symptoms: if attributable to the complication, causing significant disability or incapacity and persisting for more than a year after donation (i.e., long-term morbidity). Death: if attributable to the complication and of either possible, probable or definite imputability. TABLE 24.4 DONATION-RELATED ADVERSE EVENTS 2013 BY REACTION TYPE, SEVERITY AND COLLECTION METHOD Reaction Whole Blood (n=125,684) Rate per 10,000 Donations Plasmapheresis (n=29,585 ) Plateletpheresis (n=4,942) Events Rate Events Rate Events Rate Mild Complications Haematoma Moderate mainly characterised Mild Arterial puncture by blood Moderate outside blood vessels Delayed Mild bleeding Moderate Nerve irritation Mild Moderate Pain Nerve injury Mild Moderate Tendon damage Mild Moderate Painful arm Mild Moderate Other complications Mild Allergy (local) with local Moderate symptoms Mild 1, Immediate Without injury Moderate vasovagal Severe reaction Mild With injury Moderate Mild Delayed Without injury Moderate vasovagal reaction Mild With injury Moderate Other Complications Citrate reaction related to apheresis RBC not returned NZ BLOOD SERVICE ANNUAL HAEMOVIGILANCE REPORT 2013

53 24. Adverse Events Associated with Blood Donation continued There is a significant difference (p=<0.001) in the frequency of moderate reactions reported by whole blood donors (1:166) compared to that reported in apheresis donors (1:342). TABLE 24.5 MODERATE AND SEVERE DONATION-RELATED ADVERSE EVENTS 2013 BY COLLECTION METHOD Procedure Total Donations Whole Blood Donation 125,684 Apheresis Donation 34,527 All Donations 160,211 Severity Number Events Frequency Rate / 10,000 Donations (95%CI) Moderate 759 1: (56.3 to 64.8) Severe 1 1:125, (0.0 to 0.5) Moderate 101 1: (24.1 to 35.6) Severe (-0.2 to 1.3) Moderate 860 1: (50.2 to 57.4) Severe 1 1:160, (0.0 to 0.4) The frequency of donation-related adverse events in whole blood donors is inversely related to age and highest in donors under the age of 20 years. In this youngest group of donors, aged years, the adverse event rate is 1:15 donations and the odds ratio is 2.89 (Table 24.6). TABLE 24.6 WHOLE BLOOD DONATION-RELATED ADVERSE EVENTS 2013 BY DONOR AGE GROUP Age Group Number Adverse Events Total Donors in Age Group Frequency Rate / 1,000 Donations (95%CI) Odds Ratio (95%CI) Years ,355 1: (61.9 to 70.6) 2.89 (2.67 to 3.13) Years ,446 1: (45.6 to 52.9) 2.11 (1.94 to 2.30) Years ,335 1: (28.8 to 35.6) 1.35 (1.20 to 1.52) Years 164 8,623 1: (16.3 to 22.1) 0.79 (0.68 to 0.93) Years 151 9,642 1: (13.4 to 18.3) 0.65 (0.55 to 0.77) Years ,488 1: (12.3 to 16.7) 0.60 (0.51 to 0.70) Years ,344 1: (9.5 to 13.3) 0.47 (0.39 to 0.55) Years ,610 1: (10.6 to 14.2) 0.51 (0.44 to 0.59) Years ,582 1: (9.5 to 13.0) 0.46 (0.39 to 0.54) 60 Years ,619 1: (10.8 to 14.0) 0.51 (0.44 to 0.58) All 2, ,044 1: (23.1 to 24.7) NZ BLOOD SERVICE ANNUAL HAEMOVIGILANCE REPORT

54 24. Adverse Events Associated with Blood Donation continued Vasovagal reactions are the most common whole blood donation-related adverse event. Table 24.7 shows that, for all age groups, the rate of these events in new donors is higher than in repeat donors. There is a steady reduction in the likelihood of a vasovagal reaction with increasing age. TABLE 24.7 VASOVAGAL EVENTS 2013 BY DONOR AGE GROUP AND REPEAT DONATION New Donors Repeat Donors Age Group Total Gender Frequency Rate / 1,000 Donations (95%CI) Frequency Rate / 1,000 Donations (95%CI) Female 1: (90.9 to 112.9) 1: (34.5 to 47.0) Male 1: (48.6 to 65.7) 1: (15.6 to 26.3) Female 1: (72.1 to 112.1) 1: (32.4 to 41.3) Male 1: (58.5 to 96.6) 1: (16.6 to 24.5) Female 1: (56.5 to 109.1) 1: (20.0 to 28.5) Male 1: (43.8 to 87.9) 1: (7.6 to 13.7) Female 1: (21.9 to 68.2) 1: (10.3 to 17.6) Male 1: (23.9 to 70.9) 1: (7.2 to 13.4) Female 1: (52.0 to 121.4) 1: (7.0 to 12.7) Male 1: (17.9 to 67.5) 1: (2.1 to 5.7) Female 1: (19.9 to 81.4) 1: (5.2 to 9.7) Male 1: (32.4 to 110.5) 1: (2.2 to 5.4) Female 1: (21.2 to 86.2) 1: (3.9 to 7.8) Male 1: (14.6 to 76.6) 1: (2.7 to 6.1) Female 1: (25.7 to 103.3) 1: (5.3 to 9.3) Male 1: (30.2 to 120.3) 1: (2.3 to 5.0) Female 1: (25.5 to 128.6) 1: (5.0 to 9.1) Male 1: (-4.0 to 65.6) 1: (1.5 to 4.0) Female 1: (50.3 to 233.4) 1: (5.8 to 9.5) Male 1: (2.8 to 128.2) 1: (1.0 to 2.8) Female 1: (80.1 to 95.3) 1: (13.8 to 15.7) Male 1: (50.6 to 63.1) 1: (5.8 to 7.1) Total 1: (67.4 to 77.2) 1: (10.0 to 11.2) In line with international practice, NZBS has introduced measures to reduce the frequency of adverse reactions in younger donors. Current guidance contained in the Council of Europe Guide to the Preparation, Use and Quality Assurance of Blood Components identifies that a standard whole blood donation can be undertaken from a donor weighing at least 50kg. In younger donors, in addition, an estimate of total blood volume is made based on donor weight and height. Donors with an estimated blood volume of less than 3,500 ml are deferred from donating. 52 NZ BLOOD SERVICE ANNUAL HAEMOVIGILANCE REPORT 2013

55 25. Whole Blood Donor Vasovagal Survey For a four week period in 2013, all whole blood donors at 7 of the 11 NZBS blood collection sites were asked to complete a survey form asking if they experienced any vasovagal symptoms, and if so, what symptoms they experienced and if they had informed the collections staff of the adverse reaction. The purpose of the survey was to: A. Determine the rate of vasovagal reactions in whole blood donors B. Determine the proportion of vasovagal reactions that are reported by whole blood donors to collections staff C. Determine the proportion of vasovagal reactions, reported by whole blood donors to collections staff, that are documented as adverse events by collections staff A total of 7,325 donors completed the survey. The survey forms were completed by 90% of the donors at static collection sites compared to 86% at mobile collection sites; an overall rate of 88%. A. RATE OF VASOVAGAL REACTIONS IN WHOLE BLOOD DONORS The rate of vasovagal reactions per 1,000 donations documented by new and repeat donors is detailed in Table Data from donors older than 29 years, in which vasovagal reactions were infrequently reported, are not shown. The highest reaction rates were documented by new donors in the years age group and are 10 times greater than those reported for repeat donors in the same age group. TABLE 25.1 RATE OF VASOVAGAL REACTIONS PER 1,000 DONATIONS IN DONORS AGE YEARS BY COLLECTION SITE AND REPEAT DONATION Age Group New Donors Repeat Donors All Donors Mobile Collections Static Collections Pooled Total Collections Female Male Total Female Male Total Female Male Total B. PROPORTION OF VASOVAGAL REACTIONS REPORTED BY WHOLE BLOOD DONORS TO COLLECTIONS STAFF Of all donors who documented a vasovagal reaction, 63% reported this to collections staff (Table 25.2). New donors reported the reaction more often than repeat donors, 71% vs 59%. New donors reported the reaction more often if the donation occurred at a static rather than mobile collection site, 86% vs 66%. At mobile sites, female donors reported the reaction more often than males. The percentage of males, both new and repeat donors, reporting the reaction to collections staff was higher at static than mobile collection sites. TABLE 25.2 DONOR VASOVAGAL REACTION REPORTING BY DONOR GENDER, REPEAT DONATION AND COLLECTION SITE TYPE Repeat Donors New Donors Static Mobile Total Static Mobile Total Female 60% 61% 62% 85% 74% 77% Male 64% 43% 56% 87% 50% 59% Total 61% 57% 59% 86% 66% 71% NZ BLOOD SERVICE ANNUAL HAEMOVIGILANCE REPORT

56 25. Whole Blood Donor Vasovagal Survey continued C. PROPORTION OF DONOR REPORTED VASOVAGAL REACTIONS DOCUMENTED BY COLLECTIONS STAFF NZBS requires that staff identify and document any incident in which a donor experiences an adverse event or suffers harm as a direct consequence of the donation process (Appendix III). Where the donor documented that they had a vasovagal reaction and reported this to the collection staff, 78% were subsequently documented as adverse events by NZBS staff; 71% at static collection sites and 83% at mobile collection sites. The number of vasovagal reactions reported to the collection staff and the number documented as adverse events is detailed in Table TABLE 25.3 VASOVAGAL REACTIONS AND HAEMOVIGILANCE EVENTS BY COLLECTION SITE TYPE Reactions Reported to Collections Staff Number Events Documented by Collections Staff Percentage of Reactions Documented Static Collections % Mobile Collections % Total Collections % SURVEY SUMMARY Table 25.4 summarises the rate of vasovagal reactions per 1,000 donations documented by whole blood donors, the rate reported to the collections staff and the rate that events were documented by collections staff during the survey period. The overall 2013 donation-related vasovagal event rate is also provided. Comparing the rate of vasovagal events documented by NZBS in 2013, there is a 3.2 fold increase (220%) in the rate documented by the donors and a 2 fold increase (100%) in the rate reported to the collections staff. TABLE 25.4 WHOLE BLOOD DONOR VASOVAGAL SURVEY SUMMARY Documented by Donor Reported to Collections Staff Repeat Donors To Documented by Collections Staff tal 2013 Haemovigilance Rate Static Collections Mobile Collections Total NZ BLOOD SERVICE ANNUAL HAEMOVIGILANCE REPORT 2013

57 26. Request Form and Sample Labelling Errors The collection of a blood sample for pre-transfusion testing from the correct patient is vital for safe transfusion. Errors made in the collection of the pre-transfusion sample can lead to the transfusion of ABO incompatible red cells which can cause significant morbidity and death. International guidelines require that labels on pre-transfusion samples must be handwritten at the patient s bedside. A declaration must be signed by the collector at the time of collection of the sample certifying that: The identity of the patient was made by direct enquiry and/or inspection of their wristband. Immediately upon the blood being drawn the specimen was labelled. Samples received with a pre-printed addressograph label are not acceptable for pre-transfusion testing purposes and are discarded. Over the past eight years, the six NZBS Blood Banks (Auckland, Waikato, Palmerston North, Wellington, Christchurch and Dunedin) have been recording errors and corrective actions associated with pre-transfusion samples. Data is entered into a Microsoft Access database at each site and then analysed. Reports are reviewed by Hospital Transfusion Committees and by the NZBS Clinical Advisory Group. The minimum requirements for pre-transfusion request forms and sample labelling (for NZBS Blood Banks) are outlined in Table TABLE 26.1 NZBS PRE-TRANSFUSION REQUEST FORM AND SAMPLE LABELLING REQUIREMENTS Full name Request Form Hand-written or pre-printed label National Health Index (NHI) number and/or date of birth Gender Patient s location Details of request (group and screen, blood products etc.) Name or signature or other identifier of person completing the form Signed declaration by sample collector that The patient was positively identified prior to collection Sample labelled before leaving the patient Date and time of sample collection written on sample or form Sample Must be hand-written Family name and one or more given names (not abbreviated) NHI number and/or date of birth Signature or initials of collector During 2013, a total of 139,489 pre-transfusion samples were received by the six NZBS Blood Banks. Errors were identified in 3,405 samples/forms. The overall error rate for the six NZBS Blood Banks for 2013 was 24.4 per 1,000 samples received which is equivalent to an error rate of 1:41 samples. The error rate in 2013 was a 5.6% increase from that reported in 2012 (23.1 per 1,000 samples or 1:43). Table 26.2 details the error rate per 1,000 samples for the six NZBS Blood Banks in NZ BLOOD SERVICE ANNUAL HAEMOVIGILANCE REPORT

58 26. Request Form and Sample Labelling Errors continued TABLE 26.2 PRE-TRANSFUSION REQUEST FORM AND SAMPLE LABELLING ERRORS 2013 BY NZBS BLOOD BANK SITE Blood Bank Errors Total Samples Error Rate Rate / 1,000 Specimens (95% CI) Palmerston North 294 8,698 1: (30.2 to 37.8) Waikato ,526 1: (26.6 to 30.4) Christchurch ,552 1: (25.8 to 30.2) Wellington ,871 1: (24.6 to 28.9) Dunedin 252 9,886 1: (22.6 to 28.8) Auckland ,956 1: (16.5 to 18.8) NZBS Total 3, ,489 1: (23.6 to 25.2) The monthly and yearly mean error rate per 1,000 pre-transfusion samples received by the NZBS Blood Banks between 2009 and 2013 is detailed in Figure FIGURE 26.3 PRE-TRANSFUSION REQUEST FORM AND SAMPLE LABELLING ERROR RATE PER 1,000 SAMPLES Monthly Errors / 1,000 Samples Yearly Average Errors / 1,000 Samples Jan-09 Mar-09 May-09 Jul-09 Sep-09 Nov-09 Jan-10 Mar-10 May-10 Jul-10 Sep-10 Nov-10 Jan-11 Mar-11 May-11 Jul-11 Sep-11 Nov-11 Jan-12 Mar-12 May-12 Jul-12 Sep-12 Nov-12 Jan-13 Mar-13 May-13 Jul-13 Sep-13 Nov-13 Error Rate/ 1,000 Samples 56 NZ BLOOD SERVICE ANNUAL HAEMOVIGILANCE REPORT 2013

59 26. Request Form and Sample Labelling Errors continued The types of errors and the corrective actions taken are summarised in Table Some request forms and samples received had more than one type of error present. The total number of errors was 3,532. The most frequent type of error (20%) was declaration not signed followed by the tube being labelled with a pre-printed addressograph label or evidence that a pre-printed label had been removed (19.9%). When corrections are allowable, they must be carried out by the collector within the Blood Bank, unless the collector is directly involved in critical patient care. If the collector is not available a new pre-transfusion sample must be collected. TABLE 26.4 PRE-TRANSFUSION REQUEST FORM AND SAMPLE LABELLING ERRORS 2013 BY ERROR TYPE Error Number % Total Frequency Rate / 1,000 Specimens Declaration Not Signed % 1: Pre-printed ID Label (or Evidence of Removal) Action Required Correction by collector or Recollect % 1: Recollect Sample Not Signed % 1: Missing Patient Details (Moderate Error) Missing Patient Details (Major Error) % 1: Correction by collector or Recollect Correction by collector or Recollect % 1: Recollect Technical % 1: Recollect Signature On Sample and Declaration Differ % 1: Recollect Unlabelled Sample % 1:1, Recollect Other Clerical Errors % 1:1, Consult Team Leader Original Details Overwritten % 1:2, Recollect Total 3,532 1 Technical errors include incorrect blood collection tube type, insufficient sample, haemolysed and leaking/broken samples. The overall rate of request for re-collection of pre-transfusion samples by NZBS Blood Banks during 2013 was 16.2 per 1,000 samples received. Table 26.5 summarises the re-collection rates for each NZBS Blood Bank in Overall, 66% of errors resulted in a request for re-collection of the pre-transfusion sample. TABLE 26.5 PRE-TRANSFUSION SAMPLE RE-COLLECTION REQUESTS 2013 BY NZBS BLOOD BANK SITE Recollection Requests Total Number of Samples Frequency % Errors Requiring Re-collection Rate / 1,000 Specimens (95% CI) Palmerston North 189 8,698 1:46 64% 21.7 (18.9 to 25.0) Waikato ,526 1:52 68% 19.3 (17.7 to 20.9) Christchurch ,552 1:53 67% 18.7 (17.0 to 20.6) Wellington ,871 1:55 69% 18.3 (16.6 to 20.2) Dunedin 148 9,886 1:67 59% 15.0 (12.8 to 17.6) Auckland ,956 1:85 66% 11.7 (10.8 to 12.7) NZBS Total 2, ,489 1:62 66% 16.2 (15.6 to 16.9) NZ BLOOD SERVICE ANNUAL HAEMOVIGILANCE REPORT

60 Appendix I Transfusion Related Adverse Event Notification Form Transfusion Related Adverse Event Notification Form A. Patient Details NHI: Hospital: DOB: Sex: Male / Female Ward/clinical area: B. Transfusion & Clinical Details Date of transfusion / / Time reaction noticed am / pm Time transfusion started am/pm Volume transfused ml Event occurred during/ following transfusion with: (please circle) Red Cells Platelets Fresh Frozen Plasma Cryoprecipitate Cryodepleted Plasma Other: A Fractionated Product Reaction form (111F003) may be required. Red Cells: Platelets: Donation number(s) of unit(s) transfused Fresh Frozen Plasma: Cryoprecipitate: Cryodepleted Plasma: Patient s diagnosis, reason for transfusion & other medical/surgical history Medications & treatment C. Signs and Symptoms Baseline observations pretransfusion: Temp: Pulse: BP: RR: O 2 sat n : Observations at time of reaction: Temp: Pulse: BP: RR: O 2 sat n : Please circle relevant symptoms & provide details: Febrile: Chills / Rigors / Flushing Temperature rise: C Urticaria: Isolated / Extensive Non-urticarial rash: Respiratory: Dyspnoea / Wheeze / Stridor / Pulmonary oedema / Cough / Hypoxaemia Circulatory: Pulmonary oedema / Arrhythmia / Hypotension / Hypertension / Tachycardia / JVP GI tract: Nausea / Vomiting / Diarrhoea Pain: Chest / Loin / Abdominal / Infusion site / Other Restlessness/Anxiety: Red urine: Yes / No / Unknown Chest xray changes: Patient under anaesthesia: Yes / No No symptoms Other comments, signs, symptoms & laboratory results: (bilirubin, haptoglobin, BNP etc) HV For Haemovigilance Office Use Only National Haemovigilance Programme 111F04208 Page 1 of 4 58 NZ BLOOD SERVICE ANNUAL HAEMOVIGILANCE REPORT 2013

61 Appendix I Transfusion Related Adverse Event Notification Form continued D. Severity score Grade 1: Grade 2 (severe): Grade 3 (life-threatening): Grade 4 (death): E. Pretransfusion haematology The recipient may have required treatment but lack of such would not have resulted in permanent damage or impairment of a body function. The recipient required hospitalization or prolongation of hospitalization directly attributable to the event; and/or the adverse event resulted in persistent or significant disability or incapacity; or the adverse event necessitated medical or surgical intervention to preclude permanent damage or impairment of a body function. The recipient required major intervention following the transfusion (e.g. vasopressors, intubation, transfer to intensive care) to prevent death. The recipient died following an adverse transfusion reaction. Grade 4 should only be used if death is possibly, probably or definitely related to transfusion. If the patient died of another cause, the severity should be graded as 1, 2 or 3. If red cells transfused state pretransfusion haemoglobin: Date: Time: If platelets transfused state pretransfusion platelet count: Date: Time: If fresh frozen plasma transfused state pretransfusion INR: Date: Time: If cryoprecipitate transfused state pretransfusion fibrinogen: Date: Time: F. Nature of adverse event (definitions on back page) Allergic reaction Anaphylaxis Febrile non-haemolytic transfusion reaction Component or equipment related event Haemolytic transfusion reaction: acute / delayed Incorrect blood component/product transfused Near miss event Post-transfusion purpura (PTP) Transfusion associated circulatory overload (TACO) Transfusion associated graft vs host disease (TA-GVHD) Transfusion related acute lung injury (TRALI) Transfusion-transmitted infection (TTI) Other (please specify) Notify a Transfusion Medicine Specialist (TMS) of all severe (Grade 2 4) reactions TMS informed: Yes / No TMS name:... Date:... Time:... Blood Bank or Transfusion Nurse Specialist can notify TMS if necessary G. Imputability Score NA Not assessable When there is insufficient data for imputability assessment 1 Excluded When there is conclusive evidence beyond reasonable doubt for attributing the event to alternative causes 2 Unlikely When the evidence is clearly in favour of attributing the event to causes other than the transfusion 3 Possible When the evidence is clearly indeterminate for attributing the event either to the transfusion or alternative causes 4 Likely, probable When the evidence is clearly in favour of attributing the event to the transfusion 5 Certain When there is conclusive evidence beyond reasonable doubt for attributing the event to the transfusion Reported by: Contact Number: Date: Please note that patient identifiers will be removed for reporting to the National Haemovigilance Programme. HV For Haemovigilance Office Use Only National Haemovigilance Programme 111F04208 Page 2 of 4 NZ BLOOD SERVICE ANNUAL HAEMOVIGILANCE REPORT

62 Appendix I Transfusion Related Adverse Event Notification Form continued H. For Blood Bank/Transfusion Nurse Specialist Use Only Transfusion History Yes < 3 months Yes > 3 months No Unknown Pages 1 & 2 completed Yes / No Transfusion reaction investigation Red cell serology: Anomalies: Yes / No / Not tested Microbiology: Yes / No / Not tested Unit / Patient / Both Result: Other: Check TMS has been notified if applicable (page 2) Notification form sent by: (if different from person completing pages 1 and 2) Name:... Telephone:... Date:... Please retain a copy of pages 1 3 of this form for your records, send the original to the National Haemovigilance Office: National Haemovigilance Office New Zealand Blood Service Private Bag 7904 Wellington 6242 Phone Fax Website haemovigilance@nzblood.co.nz I. For National Haemovigilance Office Only Form received on... Acknowledgement sent... Further information requested Yes / No HV For Haemovigilance Office Use Only National Haemovigilance Programme 111F04208 Page 3 of 4 60 NZ BLOOD SERVICE ANNUAL HAEMOVIGILANCE REPORT 2013

63 Appendix I Transfusion Related Adverse Event Notification Form continued Reporting categories for transfusion-related adverse events Allergic reaction Febrile nonhaemolytic transfusion reaction (FNHTR) Component-related event Equipment-related event Haemolytic transfusion reaction Hypotensive transfusion reaction Haemosiderosis Hyperkalaemia Incorrect blood component transfused (IBCT) Near miss event Post-transfusion Purpura (PTP) Transfusion associated circulatory overload (TACO) Transfusion associated dyspnoea (TAD) Transfusion associated graft versus host disease (TA-GVHD) Transfusion related acute lung injury (TRALI) Transfusion transmitted infection (TTI) Unclassifiable complication of transfusion (UCT) Mucocutaneous signs and symptoms during or within 4 hours of transfusion: morbilliform rash with pruritus, urticaria, localised angioedema, oedema of lips, tongue and uvula, periorbital pruritus, erythema and oedema, conjunctival oedema. Anaphylactic reaction is when, in addition to mucocutaneous symptoms, there is airway compromise or cardiovascular involvement. Laryngeal symptoms include tightness in throat, dysphagia, dysphonia, hoarseness, stridor. Pulmonary symptoms include dyspnoea, cough, wheeze/bronchospasm, hypoxaemia. Cardiovascular symptoms include hypotension, hypotonia, syncope. Fever (>_ 38 C and a change of >_ 1 C from pre-transfusion value) and/or chills/rigors occurring during or within 4 hours of transfusion without other cause such as haemolytic transfusion reaction, bacterial contamination or underlying condition. An adverse event related to anticoagulant or use, misuse or defect of the bag or container occurring at some point from collection from the donor through to transfusion. Also includes use of an incorrect or inappropriate IV fluid with the component. An adverse event resulting from use, misuse or malfunction of equipment involved in the transfusion e.g. filters, infusion pumps, blood warmers, pressure devices. Acute: onset within 24 hours of transfusion. Clinical and laboratory features of haemolysis are present. May be due to red cell antibodies or non-immunological factors e.g. malfunction of a pump, blood warmer, use of hypotonic solutions etc. Delayed: Usually manifests between 24 hours and 28 days after a transfusion and signs of haemolysis are present. It may manifest as an inadequate rise of post-transfusion haemoglobin level or unexplained fall in haemoglobin. Blood group serology normally gives abnormal results confirming immunological origin. Decrease in systolic and/or diastolic blood pressure of > 30 mmhg occurring during or within one hour of completing transfusion. All other categories of adverse reactions presenting with hypotension must have been excluded together with underlying condition that could explain hypotension. Ferritin level of >_ 1000mcg/L, with or without organ dysfunction, in the setting of repeated RBC transfusions. Any abnormally high potassium level (>_ 5mmol/L or >_ 1.5 mmol/l net increase) within an hour of transfusion. Patient was transfused with a blood product that did not meet the appropriate requirements or which was intended for another patient. An error or deviation from standard procedures or policies that is discovered before the start of the transfusion and that could have led to a wrongful transfusion or a reaction in the recipient. Thrombocytopenia arising 5-12 days following transfusion of cellular blood components with findings of antibodies in the patient directed against the Human Platelet Antigen (HPA) system. Any 4 of the following: acute respiratory distress, tachycardia, increased blood pressure, acute or worsening pulmonary oedema on frontal chest radiograph, evidence of positive fluid balance. Occurring within 6 hours of completion of transfusion. An elevated BNP is supportive of TACO. Respiratory distress within 24 hours of transfusion that do not meet the criteria of TRALI, TACO, or allergic reaction. Not explained by the patient s underlying condition. Clinical syndrome characterized by fever, rash, liver dysfunction, diarrhoea, pancytopenia and findings of characteristic histological appearances on biopsy occurring 1-6 weeks following transfusion with no other apparent cause. The diagnosis of TA-GVHD is further supported by the presence of chimerism. New acute lung injury (ALI): acute onset, hypoxaemia (PaO 2 /FiO 2 < 300 mmhg, or oxygen saturation < 90% on room air, or other clinical evidence), bilateral infiltrates on frontal chest radiograph, no evidence of left atrial hypertension i.e. circulatory overload, no temporal relationship to an alternative risk factor for ALI. During or within 6 hours of completion of transfusion. Following investigation the recipient has evidence of infection post-transfusion, and there was no evidence of infection prior to transfusion and no evidence of an alternative source of infection. Occurrence of an adverse effect or reaction temporally related to transfusion, which cannot be classified according to an already defined event with no risk factor other than transfusion. HV For Haemovigilance Office Use Only National Haemovigilance Programme 111F04208 Page 4 of 4 NZ BLOOD SERVICE ANNUAL HAEMOVIGILANCE REPORT

64 Appendix II Notification of Adverse Reactions to Fractionated Blood Products NATIONAL 111F00307 NOTIFICATION OF SUSPECTED ADVERSE REACTION TO A FRACTIONATED BLOOD PRODUCT RECIPIENT Family Name First Names National Health Index No. Gender NZBS Use Address Date of Birth dd/mmm/yyyy Weight Height Relevant history: pre-existing conditions, diagnoses, pre-existing medical conditions, smoking, alcohol use, surgical procedure(s) with dates, Pregnancy with LMP, etc Pregnant Yes No Not applicable BLOOD PRODUCTS ADMINISTERED * Asterisk implicated Blood Product Blood Product(s) Manufacturer Batch Number Expiry Date Dose / Volume Date administered (start / stop) Indication(s) for Use Previous administration of this / these product(s) if any. Indicate date of commencement and dates or frequency of administration ALL OTHER MEDICINES IN USE (including Premedication/Anaesthetic agents, Over The Counter and Alternative Medicines) *Asterisk agents that may be implicated in reaction. Add further medicines on separate page if necessary Daily Dose Batch Medicine Route (with units) number Date Started Date Stopped Indications for Use / Comments DESCRIPTION OF ADVERSE REACTION OR EVENT Transfusion started / Product administered: Date Time Route: o IV o IM o Subcut o Other If the patient was receiving a course of treatment with daily / frequent doses, what were the intended dates and doses(s) of treatment: Onset of Reaction: date time. End of reaction date time or o not yet settled. For IV or Subcut Immunoglobulin: infusion rate at time of reaction, dose given on day. For freeze dried products: concentration of solution infused:, solvent used for reconstitution. Describe adverse reaction (signs, symptoms, diagnosis, course, relevant test results) continue on separate page if necessary 62 NZ BLOOD SERVICE ANNUAL HAEMOVIGILANCE REPORT 2013

65 Appendix II Notification of Adverse Reactions to Fractionated Blood Products continued NATIONAL 111F00307 Treatment of adverse reaction or event NOTIFICATION OF SUSPECTED ADVERSE REACTION TO A FRACTIONATED BLOOD PRODUCT Adverse Reaction Information Seriousness Did reaction abate after stopping blood product? Is the event serious (treatment needed to preserve life)? o Yes o No First batch: o Yes o No o Not applicable If yes, please tick at least one of the following boxes. Second batch: o Yes o No o Not applicable o Life-threatening o Death date Did reaction reappear after re-introduction? o Persistence of significant disability / incapacity First batch: o Yes o No o Not applicable o Required intervention to prevent permanent impairment / damage Second batch: o Yes o No o Not applicable o Congenital anomaly / birth defect Previous therapy with suspected blood product? o Required hospitalisation or hospitalisation was prolonged 1. o Yes o No o Not applicable o Suspected transfusion of an infectious agent Case Outcome as at dd/mmm/yyyy 2.. o Yes o No o Not applicable o Recovered dd/mmm/yyyy, Time Has suspected product been tolerated in the past? o Recovered with sequelae (specify) 1.. o Yes o No o Not applicable o Permanently disabled 2.. o Yes o No o Not applicable o Death dd/mmm/yyyy, autopsy: date or o not done If yes, dates: dd/mmm/yyyy o Not yet recovered o Unknown Causality assessment: o Highly probable o Possible o Unlikely o Unassessable Other Conditions Present (tick all that apply): o Renal Disease o Hepatic Disease o Cardiac Disease o Allergy o Respiratory Disease o Other medical conditions (list): Report type (tick all that apply) o Product used for a MedSafe-registered indication o S29 Medicine o Medication error o Overdose / Underdose o Unexpected therapeutic benefit o Lack of effect o Pregnancy o Lactation occurring o Off-label use o Misuse o Occupational exposure o Incorrect product transfused o Idiosyncratic effect o Quality defect in product REPORTER DETAILS This information will be used for follow up of the result by NZ Blood Service and will be retained only as long as needed for this review. Person Reporting the event Details of Treating Specialist/GP/Midwife if different from notifier Name & Role/Occupation: Name: If the reporter is the patient, has consent been given to contact the Treater to follow up the adverse reaction? Yes No Organisation / Address: Organisation / Address: Phone: Fax: Phone: Fax: Registrar (if relevant): Pager contact: INSTRUCTIONS 1. If the reaction or event is serious, telephone the Transfusion Medicine Specialist via a Blood Bank listed below. 2. All adverse reactions to blood products must be notified to NZ Blood Service and should be reported on this form. 3. Please fill in all sections relevant to you, your patient and the clinician responsible for treating the patient. 4. Use pre-printed identification labels for patient information, if available. Use only standard abbreviations 5. Record all medicines in use. Continue report on a separate page, if necessary, so that full information is provided. 6. Return the completed form to the Blood Bank as soon as possible. The form will then be forwarded to the NZBS National Reporting Centre. Relevant information will be forwarded to the manufacturer of the product. A non-identifying summary report may be forwarded to Medsafe and CARM. Blood Bank Telephone Fax Blood Bank Telephone Fax Blood Bank Telephone Fax Auckland Palmerston N th Christchurch Waikato Wellington Dunedin NZ BLOOD SERVICE ANNUAL HAEMOVIGILANCE REPORT