2. HEMOVIGILANCE SYSTEMS Pierre Robillard 1,2 MD 1 Québec Public Health Institute, Montréal, Canada 2 McGill University, Department of Epidemiology, Biostatistics and Occupational Health, Montréal, Canada

3. 2 What is hemovigilance A set of surveillance procedures on undesirable events/effects along the whole transfusion chain –Systematic data collection –Regular analyses of data –Interpretation of results –Dissemination of results

4. 3 What is hemovigilance Objectives –Prevent occurrence or recurrence of those undesirable events/effects –Establish priorities for intervention –Evaluate preventive measures

5. Products –Blood components (mainly) –Plasma derivatives (in some countries) In many countries under pharmacovigilance (drug post-market surveillance) Scope of national hemovigilance

6. Donations –Donor safety Undesirable effects of donations in donors –Blood safety Surveillance of ID markers in donors Surveillance of donor exclusion factors Scope of national hemovigilance

7. Surveillance of the transfusion process –Errors at blood center –Errors at the hospital –Traceability Scope of national hemovigilance

8. Recipients –Identification of transfusion-transmitted infections Traceback and lookback activities Matching recipient database with reportable disease databases Scope of national hemovigilance

9. Recipients –Surveillance of adverse transfusion events Serious only All reactions –Identification of long term effects of transfusion Matching databases –Recipient with death registry –Recipient with tumour registry –Recipient with hospital discharge database Scope of national hemovigilance

10. Blood utilization –Patterns of use of blood components Type of components Diagnosis of recipients Procedures performed on recipients –Appropriateness of use? Scope of national hemovigilance

11. 10 TYPES OF GOVERNANCE FOR HEMOVIGILANCE SYSTEMS Blood regulator –France, Switzerland, Germany Blood manufacturer –Singapore, Japan, South Africa, Ireland Professional organizations –Netherlands (TRIP), UK (SHOT) Public Health –Canada (TTISS) Public-private partnership –USA Biovigilance Network (CDC+AABB)

12. Requirements for establishing a national hemovigilance system Hospital –Personnel dedicated to blood safety Transfusion safety officer Blood bank director Chief technologist –Role Investigation and reporting of transfusion reactions and errors Training Oversee implementation of preventive measures

13. Requirements for establishing haemovigilance Hospital –Transfusion committee Multidisciplinary Review transfusion reactions Propose and evaluate preventive actions Guidelines for appropriate utiization

14. National level –Hospitals committed to participate –STANDARDIZATION Data elements to be collected DEFINITIONS of those data elements –Centralized body for analysis Expertise in transfusion medicine Expertise in surveillance Regular feedback to those who report –Establish governance for the system Requirements for establishing a haemovigilance system

15. National level –Data validation is crucial Cannot assume that definitions were followed Needed for meaningful comparisons between institutions Maybe unrealistic for all reactions but necessary for serious ones –Can be achieved through a validation committee Single Reaction specific Requirements for establishing a haemovigilance system

16. 15 QHS data validation Year 200620072008Total Total errors and ATRs reported436873491614127858 Total ATRs validated by research assistant (nurse MPH) 2984338136159980 Serious cases validated by validation committee 432 (14,5%) 448 (13,3%) 377 (10,4%) 1257 (12,6%) ATR diagnosis modified/rejected 36 (8,3%) (1,2%)l 62 (13,8%) (1,8%) 45 (11,9%) (1,2%) 143 (11,4%) (1,4%)

17. 16. Country/ region *Reports/ 1000 units What is reportable Type of system UK0.20Serious reactions + IBCT Voluntary Canada0.31Serious reactions not IBCT Voluntary Ireland1.22Serious reactions + IBCT Voluntary France2.83All reactionsMandatory Netherlands2.90All reactionsVoluntary Québec7.07All reactionsVoluntary HAEMOVIGILANCE SYSTEM Mandatory or voluntary? Year 2006

18. Reporting in haemovigilance systems FRANCEQHS TRIP

19. Trends in reporting 5 centres tested short form report for error reporting 939 1749 2874 2845 3905 4214 4671 7 388

20. Trends in reporting 3381 36 centres used short form report for errors 19 756 4671 7388 939 1749 2874 2845 3905 4214

21. 20 The Canadian Transfusion Transmitted Injuries Surveillance System (TTISS)

22. 21 Background  In collaboration with Canadian Provinces/Territories, Health Canada Regulatory and Canadian Blood Manufacturers, the Public Health Agency of Canada (PHAC) implemented a voluntary Transfusion Transmitted Injuries Surveillance System (TTISS) to monitor adverse transfusion events (ATEs)

23. Infrastructure for National TTISS Reporting National Transfusion Transmitted Injuries Surveillance System (TTISS) Public Health Agency of Canada Public Health Community Clinicians HOSPITALS Reportable Diseases Provincial/Territorial Blood Offices Adverse Events Acute Delayed Health Canada Regulatory Death = 24 hrs Severe = 15 days Reportable Diseases Blood Manufacturers Plasma Manufacturers Volunteer Reporting Mandatory Reporting

24. 23 National TTISS Working Group Membership  All provinces/territories represented  Blood manufacturers  Health Canada regulators Terms of Reference  Identify and address issues related to a national surveillance program to determine the risk of transmission of infections and injuries by blood transfusions  Recommend future directions, quality, efficacy and effectiveness of the TTISS as a national surveillance program

25. 24 National Data Review Group Membership  Members are selected for their individual medical/scientific expertise in the fields of:  public health  infectious diseases  epidemiology  transfusion medicine  Ex-officio representatives are from PHAC, Health Canada, Canadian Blood Services and Héma-Québec Terms of Reference  Reviewing and evaluating surveillance based epidemiological data concerning the risk of transmission of infections and injuries through blood, blood components and plasma derivatives  Develop research questions and hypotheses for investigation purposes  Identify signals or unusual events that should be further investigated

26. 25 Methods Data on Adverse Events is collected at the hospitals/sites Most sites voluntarily report the data to a provincial/territorial office Few sites report directly to the Public Health Agency of Canada Non-nominal data are transferred as per the provincial/federal TTISS agreement to the Public Health Agency of Canada

27. 26 Percentage of transfusions captured by TTISS (as of December 31, 2007) (2007 population/thousands) YUKON 100% Pop 32.6 NORTHWEST TERRITORIES 100% Pop 43.5 NUNAVUT Pop 31.3 BRITISH COLUMBIA 99.6% Pop 4,310.3 ALBERTA 43.3% Pop 3,510.9 SASKAT- CHEWAN 92.2% Pop 999.7 MANITOBA 86.5% Pop 1,193.5 ONTARIO 63.0% Pop 12,793.6 QUEBEC 99.6% Pop 7,686.0 NOVA SCOTIA 100% Pop 936.0 NEW BRUNSWICK 100% Pop 745.4 PEI 100% Pop 138.1 NEWFOUNDLAND & LABRADOR 93.4% Pop 506.5 Proportion captured nationally: 82% Note: Population estimates (in thousands) from Statistics Canada, as of July 1, 2007.

28. 27 Year ATEs reported to TTISS Excluded ATEs and reasons for exclusion Included ATEs from TTISS CBSMHPD Total Cases Non reportable minor event Incomplete / missing informatio n Not meeting standard definition N%1%1 N%1%1 N%1%1 N%2%2 NNN 20075408480.80-2019.243680.73920495 200661211365.35028.9105.843971.72335497 200556917685.42512.152.436363.82127411 200448910653.37437.2199.529059.32239351 ATEs reported to TTISS

29. 28 Canadian TTISS data validation

30. 29 Blood components involved in adverse transfusion events in 2007 (N=430)

31. 30 Percentage and number of ATEs by type of blood component and severity

32. 31 RBCPLT-aPLTPlasmaCryoprecipitate Multiple components Total SAAR n 24910211 - 65 %* 7.881.834.528.425.0 - 15.1 AHTR n 21-21- - 24 %* 6.8-6.91.4- - 5.6 DHTR n 39--- - - %* 12.7--- - - 9.1 TACO n 1521928- - 190 %* 49.49.131.037.8- - 44.2 All TRALI n 3113102 4 51 %* 10.19.110.313.550.0 100 11.9 TRALI n 211272 2 35 %* 6.89.16.99.550.0 8.1 Possible TRALI n 10-13 - 2 16 %* 3.2-3.4 4.1- 50.0 3.7 TAD n 12-251 - 20 %* 3.9-6.96.8 25.0 - 4.7 Bacterial contamination n 3 --- - - 3 %* 1.0 --- - - 0.7 HR n 22-37- - 32 %* 7.1-10.39.5- - 7.4 PTP n 2 --- - - 2 %* 0.6 --- - - 0.5 Other** n 2-- 2- - 4 %* 0.6 - - 2.7- - 0.9 Total n 3081129744 4 430 %* 100

33. 32 Adverse transfusion events involving bacterial contamination by relationship to transfusion, 2004-2007

34. 33

35. 34 Transfusion-related fatalities 2007 Adverse eventDefiniteProbablePossibleTotal N%N%N%N% TACO--342.9571.4857.1 TRALI--228.6--214.3 Possible TRALI--114.31 2 TAD--114.3--17.1 AHTR----114.317.1 Total0071007 14100

36. 35 Transfusion Errors Surveillance System (TESS) Pilot Project – Data 2005-7

37. 36 Background TESS is an abbreviated error tracking system designed for non-academic use  implement a tool for systematic capture of errors, including near-misses  Coding scheme comparable to what is now being used in USA biovigilance network

38. 37 Methods Actual event vs. Near-miss Severity Description HighPotential for serious injury or death MediumPotential for minor harm LowNo realistic potential for harm TypeDescription 1Actual – harm 2Actual – no harm 3Near-miss – unplanned recovery 4Near-miss - planned recovery

39. 38 Hospital sites’ size Total <2,000 RBC transfusions/year3 2,000 – 10,000 RBC transfusions/year5 >10,000 RBC transfusions/year3 Total11

40. 39 ERRORS REPORTED TOTAL 31,989  200510,273  2006 9,918  200711,798  No recovery-harm23 (0.1%)  No recovery-no harm919 (2.9%)  Near miss- unplanned rec.742 (2.3%)  Near miss- planned rec.30,305 (94.7%) Total: 31,989

41. 40 Errors by severity and site size 2005-2007 Severity Size HighMediumLowTotal Small 233 (10.4%)108 (4.8%)1907 (84.8%)2248 Medium 1093 (8.4%)1330 (10.3%)10,530 (81.3%)12,953 Large 1643 (9.8%)1149 (6.8%)13,993 (83.4%)16,785 TOTAL 2969(9.3%)2587 (8.1%)26,430 (82.6%)31,986* * 3 severity not specified Chi-square: 3.37; p=0.067 comparing small vs medium+large

42. 41 Figure 2. Point of detection of error in the transfusion process Event did not involve a product (0.4%), Other (4.1%) are not shown BEFORE ISSUEAFTER ISSUE 54.6% 40.9%

43. 42 Actions taken 2005-2007 N% No action 1,6735.2 Product retrieved 4371.4 Product denied 2360.7 Record corrected 8,32426.0 Floor/clinic notified 12,33838.6 Additional testing 1,2764.0 Patient sample recollected 6,18119.3 Product destroyed 1,7245.4 Other 5,95818.6

44. 43 Delay between Occurrence and Discovery 2005-2007 N% Same day18,26957.1 Next day4,29713.4 2 days1,0393.2 3-6 days1,9636.1 7-13 days1,2553.9 14-29 days1,5364.8 ≥ 1 month3,63011.3 TOTAL*31,989100.0

45. 44 Person Involved in Error 2005-2007 N% Nurse14,89446.6 Technologist1271039.7 MD / DO20866.5 Clerk3661.1 Lab Assistant4531.4 Supplier3741.2 Supervisor550.2 QA/TSO100.09 Other9983.1 TOTAL31,986* *3 not specified

46. 45 Occurrence Location N% Blood Supplier2450.8 Emergency454914.2 Intensive Care Unit318610.0 Laboratory Service3781.2 Medical/Surgical Ward557917.4 Obstetrics14144.4 Operating Room20706.5 Out Patient Procedures13944.4 Out Patients11383.6 Supplier3051.0 Transfusion Service11,73136.7 TOTAL31,989100.0 2005-2007

47. 46 Type of errors reported Clinical2005-2007 N% PRProduct/Test Request21226.6 SCSample Collection938229.3 SHSample Handling25217.9 RPRequest for Pick-up4961.6 UTUnit Transfusion487615.2 DCDonor Codes4521.4 MSMiscellaneous3411.1

48. 47 Type of errors reported Laboratory2005-2007 N% PCProduct Check-in19066.0 SRSample Receipt13654.3 STSample Testing401812.6 USUnit Storage15935.0 AVAvailable for Issue3081.0 SEUnit Selection1050.3 UMUnit Manipulation6252.0 UIUnit Issue18795.9

49. 48 PC PR SC SH SR ST SE US UM UI UT RP DC Rates for General Event Codes 1:353 1:257 1:48 1:180 1:333 1:371 1:6111 1:422 1:1027 1:327 1:132 1:1098 1:1488 2005-2007

50. 49 Rates for Product/Test Request 1:842 1:8786 1:3681 1:2898 1:1325 PR 02 PR 03 PR 04 PR 06 PR 99 PR 01 PR 05 1:869 1:13,968 2005-2007

51. 50 Rates for Sample Collection Errors 1:1805 1:1625 1:9098 1:2357 1:152 1:158 1:199 1:3345 1:2861 SC 01 SC 02 SC 03 SC 04 SC 06 SC 07 SC 08 SC 10 SC 99 SC 05 SC 09 1:4026 1:26,758 1:30,326 SC 11 2005-2007

52. 51 Rates for Sample Handling 1:427 1:1330 1:2013 1:1756 SH 02 SH 03 SH 04 SH 06 SH 99 SH 01 SH 05 1:5547 1:3472 2005-2007 1:2263 SH 07 1:20,677 1:2357 SH 10

53. 52 Rates for Request for Pick-Up 1:9905 1:13,287 1:17,573 1:11,591 RP 02 RP 03 RP 04 RP 06 RP 99 RP 01 RP 05 1:11,843 1:4,289 RP 10 2005-2007 1:38,911 1:4035

54. 53 1:87,792 1:175 Rates for Unit Transfusion Errors UT 01 1:2259 1:801 1:29,264 1:87,792 1:61,454 1:122,909 1:2845 UT 02 UT 03 UT 04 UT 05 UT 07 UT 08 UT 19 UT 21 UT 99 1:40,970 1:38,409 UT 11 UT 12 UT 13 1:614,543 1:61,454 UT 06 UT 10 1:307,272 1:61,454 2005-2007

55. 54 Data utilization Setting priorities for transfusion safety Evaluation of implementation of preventive measures France: –Traceability –Bacterial contaminations UK –ABO mistransfusions –TRALI Québec –Bacterial contaminations –ABO mistransfusions

56. 55 Traceability FRANCE

57. 56 Bacterial contaminations FRANCE

58. 57 ABO incompatible red cell transfusions 1996 - 2005

59. 58 Cases of TRALI with relevant donor antibody analysed by implicated component and by year 2003-2005

60. N ABO mistransfusions QUÉBEC

61. Online transfusion history K In the period May 2003- Nov. 2005  All Québec hospitals were progressively computerized with the same blood bank software K A query tool was added  Each hospital can query the BB database of all other hospitals to see if patient is present  If so information will appear on screen:  Blood group, irregular antibodies  Previous transfusions  Previous transfusion reactions, special requirements  This information can be compared with current info or test results on patients  Information cannot be saved and disappear from screen upon leaving the query tool.

62. Effect of inter-hospital online transfusion history consultation p=0.012 p=0.03 p=0.006 Ratio per 100,000 RBCs

63. 62 Frequencies and Ratios/100,000 BC - Platelet pools NRate Diversion pouch * Bacterial detection

64. 63 Pre-post for diversion pouch WBDPC YearNRate 2000-2002181:2,655 2003-200411:27,737 Pre-post for diversion pouch + bacterial detection WBDPC X 2 =8.09, p = 0.004 YearNRate 2000-2002181:2,655 2003-200811:57,713 X 2 = 17.7, p < 0.001

65. 64 International comparisons

66. 65 International Surveillance of Transfusion Adverse Reactions and Events ISTARE Project The Working Group C. Politis, D. Rebibo, C. Richardson, P. Robillard, J. Wiersum

67. 66 Purpose of Database Information sharing Surveillance, Monitoring Analysing data Potential Uses Benchmarking for countries Risk assessment

68. 67 What data? General information –On the country’s haemovigilance system and coverage Denominators general - for donors/ donations and major categories of products Denominators specific - for products Adverse events in donors related to donation Errors – IBCT Adverse reactions in patients that are possibly, probably, or definitely associated with transfusion

69. 68 Pilot Studies Data have been collected in 3 rounds 2006-7, 2008, 2009 18 countries have participated in at least one round

70. 69 General information, 2009 14 haemovigilance systems –13 national –1 regional In terms of total blood supply: - half have 100% coverage and two >90% - three more are in the range 80-89%

71. 70 Volume of data, 2009 14,553 total adverse reactions 18,127,713 units issued Rate 77:100,000

72. 71 Typen% TRALI1326.5 TACO918.4 TAD612.2 AHTR612.2 Allergic4 8.2 Trans-ass GvHD24.1 Post-tr purpura12.0 DHTR12.0 Other 714.3 Total49100.0 Adverse Transfusion Reactions, 2009 Total deaths 33.7/10.000 ARs 2.7/ million issued blood components Rates

73. 72 Incidence of adverse reactions by type of products general – 2007- 2008-2009 Per 100,000 units issued

74. 73 Incidence of adverse reactions by type of products specific – 2009 Per 100,000 units issued : 8 countries

75. 74 Incidence of all adverse reactions by country – 2007-2008-2009 Per 100,000 units issued

76. 75 Incidence of Bacterial Infections by country 2007-2008-2009 Per 100,000 units issued

77. 76 Incidence of allergic reactions by country – 2007-2008-2009 Per 100,000 units issued

78. 77 Incidence of FNHTR by country 2007-2008-2009 Per 100,000 units issued

79. 78 Incidence of TRALI by country 2007-2008-2009 Per 100,000 units issued

80. 79 Incidence of TACO by country 2007-2008-2009 Per 100,000 units issued

81. 80 Incidence of TAD by country 2007-2008-2009 Per 100,000 units issued

82. 81 CONCLUSION Hemovigilance is now an integral part of a quality system in transfusion Hemovigilance covers donors, processes and recipients Hemovigilance helps identify priorities for transfusion safety and monitors effects of preventive measures Hemovigilance works