Transfusion transmitted injuries surveillance system (TTISS ): 2009 - 2013 Summary Results

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Organization: Public Health Agency of Canada

Type: Publication

Information to the reader of the 2009-2013 transfusion transmitted surveillance system (TTISS) summary results

The Centre for Communicable Diseases and Infection Control (CCDIC) of the Public Health Agency of Canada (the Agency) is pleased to present Transfusion Transmitted Injuries Surveillance System (TTISS) Summary Results, 2009-2013. This summary report presents transfusion transmitted injuries surveillance data submitted by Canadian hospitals participating in the Transfusion Transmitted Injuries Surveillance System (TTISS).

The TTISS is a pan-Canadian surveillance system established by the Agency to capture non-nominal data on adverse transfusion reactions in Canadian hospitals providing transfusion services. The overarching goal of the TTISS is to improve patient safety in Canadian hospitals.

CCDIC in partnership with participating hospitals is responsible for the collection, management and analysis of the TTISS data, as well as the production of reports summarizing key findings. CCDIC supports the use of these data to inform public health and policy action. In addition, CCDIC supports the Agency’s ongoing commitment to improving data quality, and to defining and setting surveillance standards.

Summary

Transfusion Transmitted Injuries Surveillance System (TTISS) has been monitoring adverse reactions related to the transfusion of blood components, and blood products (plasma derivatives) since 2001 in Canada. As of 2007, all provinces and the Northwest and Yukon territories participate in the TTISS. The participation rate of hospitals providing transfusion services in each of these provinces and territories (P/Ts) increased gradually over time: by 2013, it was between 80% and 100% in 11 P/Ts. Only one province had a participation rate of less than 50%. The TTISS coverage is also measured by the volume of blood components (red blood cells, granulocytes, platelets, plasma and cryoprecipitates) transfused annually and, approximately 1.5 million transfusions were given in Canada each year from 2009 to 2013. Approximately 80% of these transfusions were monitored by the TTISS network.

In addition to the overall counts and proportions of adverse reactions from transfusion of blood components and blood products (plasma derivatives), this report also provides the overall and annual risks of individual adverse reactions resulting from the transfusion of blood components during the five year period 2009-2013. These statistics could not be calculated for blood products (plasma derivatives) because of the lack of appropriate corresponding denominator data. Minor allergic reactions as well as febrile non-hemolytic reactions were excluded as a result of inconsistent reporting of adverse transfusion reactions over the years. Also, the doubtful, ruled out and missing responses for the relationship of adverse event with transfusion have not been considered in the report.

A total of 3,369 cases of transfusion-related adverse reactions were reported to the TTISS from 2009 to 2013: from 465 in 2009 to 874 in 2013, corresponding to an overall five-year increase of 88% (annual increase of 17.5%). The surveillance protocol requires participants to send comprehensive reports on the transfusion reactions such as transfusion-associated circulatory overload (TACO), Severe anaphylactic & anaphylactoid reactions - SAAR (include anaphylactic shocks), hypotensive reaction, acute and delayed hemolytic reaction, transfusion-related acute lung injury (TRALI), transfusion-associated dyspnea (TAD), IVIG associated reaction, aseptic meningitis, bacterial/viral infections, and unusual reactions of clinical significance. Each reported adverse reaction is categorized not only by its severity level (which is measured by the level of medical care/intervention required for a patient as a result of developing the reaction), but also by their resulting outcome which assesses whether the patient sustained any physiological and/or physical consequence (damage/impairment of a body function) following the development of the reaction. The outcome varies from minor to major/long-term sequelae including death. In 2013, the TTISS recorded 6 deaths were determined to be related to the transfusion of blood components. Of these, two were deemed to be definitely related to: (i) bacterial contamination of transfused platelets with alpha-hemolytic streptococcus and, (ii) incompatible transfusion whereby a B Rh+ blood component (red blood cells) was transfused to an A Rh+ patient.  Three deaths were determined to be possibly related to transfusion: (i) TACO, (ii) possible TRALI, and (iii) delayed hemolytic reaction. The last case with a probable link with the transfusion of blood component was determined to be a possible TRALI. There were no reported transfusion-related deaths for blood products.

1. Overall adverse transfusion-related reactions

Table 1A: Adverse reactions resulting from transfusion of blood components and blood products (plasma derivatives), TTISS 2009-2013
Type of transfusion-related adverse reaction 2009 2010 2011 2012 2013 Total
Freq. % Freq. % Freq. % Freq. % Freq. % Freq. %
Transfusion-associated circulatory overload (TACO) 149 32.0% 190 30.7% 223 34.7% 220 28.6% 255 29.2% 1,037 30.8%
Acute hemolytic reaction (AHR) 25 5.4% 32 5.2% 24 3.7% 31 4.0% 51 5.8% 163 4.8%
Severe anaphylactic & anaphylactoid reactions (SAAR) 65 14.0% 96 15.5% 61 9.5% 87 11.3% 121 13.8% 430 12.8%
Hypotensive reaction (HR) 41 8.8% 44 7.1% 37 5.8% 66 8.7% 57 6.5% 245 7.3%
Delayed hemolytic reaction (DHR) 65 14.0% 62 10.0% 71 11.1% 84 10.9% 81 9.3% 363 10.8%
Transfusion-related acute lung injury (TRALI) 10 2.2% 8 1.3% 13 2.0% 8 1.0% 3 0.3% 42 1.2%
Possible TRALI 9 1.9% 14 2.3% 9 1.4% 13 1.7% 8 0.9% 53 1.6%
Transfusion-associated dyspnea - TAD 19 4.1% 39 6.3% 19 3.0% 24 3.1% 63 7.2% 164 4.9%
IVIG-associated reaction 24 5.2% 39 6.3% 54 8.4% 105 13.7% 146 16.7% 368 10.9%
Aseptic meningitis 1 0.2% 10 1.6% 3 0.5% 13 1.7% 15 1.7% 42 1.2%
Incompatible transfusion 7 1.5% 7 1.1% 10 1.6% 10 1.3% 3 0.3% 37 1.1%
Bacterial infection 4 0.9% 7 1.1% 9 1.4% 3 0.4% 0 0.0% 23 0.7%
OtherTable 1 - Footnote 1 37 8.0% 52 8.4% 98 15.3% 76 9.9% 71 8.1% 334 9.9%
Unusual reactionsTable 1 - Footnote 2 9 1.9% 19 3.1% 11 1.7% 28 3.6% 0 0.0% 67 2.0%
Total 465 100% 619 100% 642 100% 768 100% 874 100% 3,368 100%

Over the 2009-2013 period, transfusion-associated circulatory overload (TACO), severe anaphylactic & anaphylactoid reactions (SAAR), IVIG-associated reactions and delayed hemolytic reactions were the most commonly reported adverse reactions. Collectively, they accounted for more than 65% (n=2,198) of all the reported adverse transfusion reactions (Table 1A).

Table 1B: Adverse reactions related to transfusion of blood components, TTISS 2009 – 2013
Type of transfusion-related adverse reaction 2009 2010 2011 2012 2013 Total
Freq. % Freq. % Freq. % Freq. % Freq. % Freq. %
Transfusion-associated circulatory overload (TACO) 141 41. 8% 185 40. 8% 216 48. 4% 209 41.6% 243 42.9% 994 43.1%
Acute hemolytic reaction (AHR) 14 4.2% 16 3.5% 15 3. 4 % 14 2.8% 17 3.0% 76 3.3%
Severe anaphylactic & anaphylactoid reactions (SAAR) 50 14. 8% 79 17.4% 46 10.3% 65 12.9% 106 18.6% 346 15. 0%
Hypotensive reaction (HR) 34 10. 1% 40 8.8% 30 6.7% 63 12. 5% 49 8.5% 216 9.3%
Delayed hemolytic reaction (DHR) 38 11. 3% 31 6.8% 37 8.3% 38 7. 6 % 41 7.1% 185 8.0%
Transfusion-related acute lung injury (TRALI) 8 2.4% 7 1.5% 12 2.7% 8 1.6% 3 0.5% 38 1.7%
Possible TRALI 9 2.7% 14 3.1% 8 1.8% 13 2.6% 8 1.4% 52 2.3%
Transfusion-associated dyspnea - TAD 16 4.7% 34 7. 5% 18 4.0% 20 4.0% 47 8.2% 135 5.8%
Incompatible transfusion 7 2.1% 6 1.3% 8 1.8% 10 2.0% 3 0.5% 34 1.5%
Bacterial infection 4 1.2% 7 1.5% 9 2.0% 3 0. 4% 0 0.0% 23 1.0%
Other 7 2.1% 21 4.6% 39 8.7% 36 7. 2% 53 9.2% 156 6.7%
Unusual reactions 9 2.7% 13 2.9% 8 1.8% 25 4.8% 0 0.0% 55 2.3%
Total 337 100% 453 100% 446 100% 504 100% 570 100% 2,310 100%

Adverse reactions related to the transfusion of blood components (Table 1B) accounted for 68.6% (n=2,310) of all reported adverse reactions. Transfusion-associated circulatory overload (TACO) and severe anaphylactic & anaphylactoid reactions (SAAR) were the most commonly reported and represented respectively 43.1% (n=994) and 15.0% (n=346) of the cases (Table 1B). Transfusion-related lung injury (TRALI) and possible TRALI accounted for just 4% and unlike TACO and SAAR that increased respectively by 14% and 63% in 2013, they decreased significantly by 48%.

Table 1C: Adverse reactions related to transfusion of blood products (plasma derivatives), TTISS 2009 – 2013
Type of transfusion-related adverse reaction 2009 2010 2011 2012 2013 Total
Freq. % Freq. % Freq. % Freq. % Freq. % Freq. %
Transfusion-associated circulatory overload (TACO) 8 6.3% 5 3.0% 7 3.6% 11 4.2% 12 4.0% 43 4.1%
Acute hemolytic reaction (AHR) 11 8.6% 16 9.6% 9 4.6% 17 6.4% 34 11.2% 87 8.2%
Severe anaphylactic & anaphylactoid reactions (SAAR) 15 11.7% 17 10.2% 15 7.7% 22 8.3% 15 5.0% 84 7.9%
Hypotensive reaction (HR) 7 5.5% 4 2.4% 7 3.6% 3 1.1% 8 2.6% 29 2.7%
Delayed hemolytic reaction (DHR) 27 21.1% 31 18.7% 34 17.3% 46 17.4% 40 13.2% 178 16.8%
Transfusion-related acute lung injury (TRALI) 2 1.6% 1 0.6% 1 0.5% 0 0.0% 0 0.0% 4 0.4%
Possible TRALI 0 0.0% 0 0.0% 1 0.5% 0 0.0% 0 0.0% 1 0.1%
Transfusion-associated dyspnea - TAD 3 2.3% 5 3.0% 1 0.5% 4 1.5% 16 5.3% 29 2.7%
IVIG-associated reaction 24 18.8% 39 23.5% 54 27.6% 105 39.8% 146 48.2% 368 34.8%
Aseptic meningitis 1 0.8% 10 6.0% 3 1.5% 13 4.9% 15 5.0% 42 4.0%
Incompatible transfusion 0 0.0% 1 0.6% 2 1.0% 0 0.0% 0 0.0% 3 0.3%
Other 30 23.4% 31 18.7% 59 30.1% 40 15.2% 18 5.6% 178 16.7%
Unusual reactions 0 0.0% 6 3.6% 3 1.5% 3 1.1% 0 0.0% 12 1.1%
Total 128 100% 166 100% 196 100% 264 100% 304 100% 1,058 100%

The most common of the adverse reactions related to transfusion of blood products (plasma derivatives) were IVIG-associated reactions, followed by delayed hemolytic reactions that accounted respectively for 34.8% (n=368) and 16.8% (n=178) of the cases recorded between 2009 and 2013. While the number of cases of delayed hemolytic reactions stayed almost unchanged from 2009 to 2011 and from 2012 to 2013 (Table 1C), that of IVIG-associated reactions has steadily increased significantly over time going from 24 cases per year in 2009 to 146 in 2013 (Table 1C).

2. Imputability (i.e. relationship of adverse reactions to transfusion)

Table 2A: Relationship of adverse reaction to transfusion of blood components & blood products (i.e. imputability), TTISS 2009-2013
Type of transfusion-related adverse reaction DefiniteTable 2A - Footnote 1 ProbableTable 2A - Footnote 2 PossibleTable 2A - Footnote 3 Total
Freq. % Freq. % Freq. % Freq. %

N.B. Cases for which the relationship to transfusion was missing, doubtfulTable 2A - Footnote 4 or ruled outTable 2A - Footnote 5 were excluded from the analysis.

Transfusion-associated circulatory overload (TACO) 69 6.7% 475 45.8% 493 47.5% 1,037 100%
Acute hemolytic reaction (AHR) 74 45.4% 62 38.0% 27 16.6% 163 100%
Severe anaphylactic & anaphylactoid reactions (SAAR) 51 11.9% 278 64.7% 101 23.5% 430 100%
Hypotensive reaction (HR) 9 3.7% 77 31.7% 159 64.6% 245 100%
Delayed hemolytic reaction (DHR) 211 58.1% 109 30.0% 43 11.8% 363 100%
Transfusion-related acute lung injury (TRALI) 10 23.8% 21 50.0% 11 26.2% 42 100%
Possible TRALI 6 11.3% 13 24.5% 34 64.2% 53 100%
Transfusion-associated dyspnea (TAD) 3 1.8% 71 43.3% 90 54.9% 164 100%
IVIG-associated reactions 39 10.6% 261 70.9% 68 18.5% 368 100%
Aseptic meningitis 6 14.3% 27 64.3% 9 21.4% 42 100%
Incompatible transfusion 29 78.4% 4 10.8% 4 10.8% 37 100%
Bacterial infection 1 4.3% 4 17.4% 18 78.3% 23 100%
Other 23 6.9% 184 55.1% 127 38.0% 334 100%
Unusual reactions 1 1.5% 16 23.9% 50 74.6% 67 100%
Total 532 15.8% 1,602 47.6% 1,234 36.6% 3,368 100%
Table 2B: Relationship of adverse reaction to transfusion of blood components (i.e. imputability), TTISS 2009-2013
Type of transfusion-related adverse reaction Definite Probable Possible Total
Freq. % Freq. % Freq. % Freq. %
Transfusion-associated circulatory overload (TACO) 67 6.7% 461 46.4% 466 46.8% 994 100%
Acute hemolytic reaction (AHR) 40 52.6% 24 31.6% 12 15.8% 76 100%
Severe anaphylactic & anaphylactoid reactions (SAAR) 30 8.7% 230 66.7% 86 24.6% 346 100%
Hypotensive reaction (HR) 6 2.8% 67 31.2% 143 66.0% 216 100%
Delayed hemolytic reaction (DHR) 125 67.9% 43 22.8% 17 9.2% 185 100%
Transfusion-related acute lung injury (TRALI) 9 21.1% 19 50.0% 11 28.9% 38 100%
Possible TRALI 6 11.5% 12 23.1% 34 65.4% 52 100%
Transfusion-associated dyspnea - TAD 3 2.2% 54 39.6% 78 58.2% 135 100%
Incompatible transfusion 29 85.3% 1 2.9% 4 11.8% 34 100%
Bacterial infection 1 4.5% 4 13.6% 18 81.8% 23 100%
Other 9 5.8% 75 47.7% 72 46.5% 156 100%
Unusual reactions 0 0.0% 13 22.2% 42 77.8% 55 100%
Total 324 14.1% 1003 43.4% 983 42.6% 2,310 100%

Overall, only 15.8% (n = 532) of the cases were definitely linked to transfusion (Table 2A), while the remaining 84.2% were deemed to be probably (n = 1,602) or possibly (n = 1,234) related to transfusion. Almost 61% (n = 324) of the cases definitely linked to transfusion were patients that received blood component (Table 2B).

Table 2C: Relationship of adverse reaction (imputability) to transfusion of blood products (plasma derivatives), TTISS 2009-2013
Type of transfusion-related adverse reaction Definite Probable Possible Total
Freq. % Freq. % Freq. % Freq. %
Transfusion-associated circulatory overload (TACO) 2 4.7% 14 32.6% 27 62.8% 43 100%
Acute hemolytic reaction (AHR) 34 39.1% 38 43.7% 15 17.2% 87 100%
Severe anaphylactic & anaphylactoid reactions (SAAR) 21 25.0% 48 57.1% 15 17.9% 84 100%
Hypotensive reaction (HR) 3 10.3% 10 34.5% 16 55.2% 29 100%
Delayed hemolytic reaction (DHR) 86 48.3% 66 37.1% 26 14.6% 178 100%
Transfusion-related acute lung injury (TRALI) 2 50.0% 2 50.0% 0 0.0% 4 100%
Possible TRALI 0 0.0% 1 100% 0 0.0% 1 100%
Transfusion-associated dyspnea -TAD 0 0.0% 17 58.6% 12 41.4% 29 100%
IVIG-associated reactions 39 10.6% 261 70.9% 68 18.5% 368 100%
Aseptic meningitis 6 14.3% 27 64.3% 9 21.4% 42 100%
Incompatible transfusion 0 0.0% 3 100% 0 0.0% 3 100%
Other 14 7.9% 109 61.0% 55 31.1% 178 100%
Unusual reactions 1 8.3% 3 25.0% 8 66.7% 12 100%
Total 208 19.7% 599 56.6% 251 23.7% 1,058 100%

Of the adverse reactions from blood product/plasma derivative approximately 19.7% (n = 208) were determined as being definitely transfusion-related, 56.6% (n = 599) as being probably related to transfusion and the remaining 23.7% (n = 251) were deemed to have possible link to transfusion (Table 2C).

3. Severity of adverse transfusion-related reactions

Approximately 60% (n = 1,998) of adverse transfusion reactions reported between 2009 and 2013 were of grade 1 severity level (i.e. no permanent damage or impairment of a bodily function).

3.1. Grade 2Footnote 1 severity (or severe) adverse reactions:

Table 3A: Severe (Grade 2) adverse reactions from transfusion of blood components, TTISS 2009-2013
Type of transfusion-related adverse reaction 2009 2010 2011 2012 2013 Total
Freq. % Freq. % Freq. % Freq. % Freq. % Freq. %
Transfusion-associated circulatory overload (TACO) 32 40.0% 79 38.3% 93 50.3% 95 43.8% 74 43.3% 373 43.4%
Acute hemolytic reaction (AHR) 1 1.3% 5 2.4% 8 4.3% 6 2.8% 7 4.1% 27 3.1%
Severe anaphylactic & anaphylactoid reactions (SAAR) 21 26.3% 58 28.2% 35 18.9% 47 21.7% 50 29.2% 211 24.6%
Hypotensive reaction (HR) 3 3.8% 12 5.8% 8 4.3% 18 8.3% 7 4.1% 48 5.6%
Delayed hemolytic reaction (DHR) 4 5.0% 9 4.4% 8 4.3% 14 6.5% 12 7.0% 47 5.5%
Transfusion-related acute lung injury (TRALI) 5 6.3% 3 1.5% 6 3.2% 3 1.4% 0 0.0% 17 2.0%
Possible TRALI 4 5.0% 8 3.9% 4 2.2% 9 4.1% 3 1.8% 28 3.3%
Transfusion-associated dyspnea (TAD) 3 3.8% 14 6.8% 8 4.3% 6 2.8% 12 7.0% 43 5.0%
Incompatible transfusion 1 1.3% 1 0.5% 3 1.6% 4 1.8% 1 0.6% 10 1.2%
Bacterial infection 2 2.5% 5 2.4% 4 2.2% 3 1.4% 0 0.0% 14 1.6%
Other 3 3.8% 10 4.9% 7 3.8% 8 3.7% 5 2.9% 33 3.8%
Unusual reactions 1 1.3% 2 1.0% 1 0.5% 4 1.8% 0 0.0% 8 0.9%
Total 80 100% 206 100% 185 100% 217 100% 171 100% 859 100%

Over 37% (n = 859) of the 2,302 adverse reactions recorded between 2009 and 2013 from the transfusion of blood components were deemed to be of grade 2 severity i.e. the patients involved sustained a condition serious enough to require hospitalization or prolonged hospitalization, medical/surgical intervention (Table 3A). The majority of these adverse reactions have consistently been identified under TACO or severe anaphylactic & anaphylactoid reactions (SAAR) which collectively accounted for more than two third of the cases (Table 3A). As for the adverse reactions of the same severity level but from the transfusion of blood products, the most predominant were hemolytic reactions (both acute and delayed), followed by SAAR and aseptic meningitis (Table 3B).

Table 3B: Severe (Grade 2) adverse reactions from transfusion of blood products, TTISS 2009-2013
Type of transfusion-related adverse reaction 2009 2010 2011 2012 2013 Total
Freq. % Freq. % Freq. % Freq. % Freq. % Freq. %
Transfusion-associated circulatory overload (TACO) 2 6.7% 1 1.9% 3 4.8% 5 7.9% 3 4.4% 14 5.1%
Acute hemolytic reaction (AHR) 4 13.3% 7 13.5% 7 11.3% 7 11.1% 18 26.5% 43 15.6%
Severe anaphylactic & anaphylactoid reactions (SAAR) 4 13.3% 8 15.4% 12 19.4% 19 30.2% 7 10.3% 50 18.2%
Hypotensive reaction (HR) 2 6.7% 2 3.8% 0 0.0% 0 0.0% 1 1.5% 5 1.8%
Delayed hemolytic reaction (DHR) 14 46.7% 11 21.2% 22 35.5% 9 14.3% 14 20.6% 70 25.5%
Transfusion-related acute lung injury (TRALI) 1 3.3% 0 0.0% 0 0.0% 0 0.0% 0 0.0% 1 0.4%
Transfusion-associated dyspnea (TAD) 1 3.3% 1 1.9% 1 1.6% 1 1.6% 1 1.5% 5 1.8%
IVIG headache 0 0.0% 0 0.0% 3 4.8% 7 11.1% 7 10.3% 17 6.2%
Aseptic meningitis 1 3.3% 8 15.4% 3 4.8% 9 14.3% 11 16.2% 32 11.6%
Incompatible transfusion 0 0.0% 1 1.9% 1 1.6% 0 0.0% 0 0.0% 2 0.7%
Other 1 3.3% 11 21.2% 10 16.1% 6 9.5% 6 8.8% 34 12.4%
Unusual reactions 0 0.0% 2 3.8% 0 0.0% 0 0.0% 0 0.0% 2 0.7%
Total 30 100% 52 100% 62 100% 63 100% 68 100% 275 100%

3.2. Grade 3Footnote 2 severity (or life-threatening) adverse reactions:

Table 3C: Life-threatening (Grade 3) adverse reactions from transfusion of blood components, TTISS 2009-2013
Type of transfusion-related adverse reaction 2009 2010 2011 2012 2013 Total
Freq. % Freq. % Freq. % Freq. % Freq. % Freq. %
Transfusion-associated circulatory overload (TACO) 9 42.9% 14 35.9% 16 45.7% 15 36.6% 7 30.4% 61 38.4%
Acute hemolytic reaction (AHR) 0 0.0% 3 7.7% 0 0.0% 0 0.0% 4 17.4% 7 4.4%
Severe anaphylactic & anaphylactoid reactions (SAAR) 2 9.5% 5 12.8% 4 11.4% 10 24.4% 1 4.3% 22 13.8%
Hypotensive reaction (HR) 0 0.0% 1 2.6% 2 5.7% 3 7.3% 1 4.3% 7 4.4%
Delayed hemolytic reaction (DHR) 0 0.0% 0 0.0% 0 0.0% 0 0.0% 1 4.3% 1 0.6%
Transfusion-related acute lung injury (TRALI) 1 4.8% 4 10.3% 6 17.1% 3 7.3% 0 0.0% 14 8.8%
Possible TRALI 4 19.0% 6 15.4% 3 8.6% 4 9.8% 5 21.7% 22 13.8%
Transfusion-associated dyspnea (TAD) 1 4.8% 4 10.3% 0 0.0% 1 2.4% 1 4.3% 7 4.4%
Incompatible transfusion 2 9.5% 0 0.0% 0 0.0% 0 0.0% 0 0.0% 2 1.3%
Bacterial infection 0 0.0% 1 2.6% 2 5.7% 0 0.0% 0 0.0% 3 1.9%
Other 1 4.8% 1 2.6% 1 2.9% 1 2.4% 3 13.0% 7 4.4%
Unusual reactions 1 4.8% 0 0.0% 1 2.9% 4 9.8% 0 0.0% 6 3.8%
Total 21 100% 39 100% 35 100% 41 100% 23 100% 159 100%

The majority (159 of the 175) of the cases of grade 3 severity (i.e. life-threatening) adverse reactions from 2009 to 2013 was recorded from the transfusion of blood components 2013(Table 3C). In 2013 the ascending pattern of the total number of cases reported annually observed since 2009 abruptly decreased by about 44% (from 41 in 2012 to 23 in 2013. This decline was almost entirely due to the significant reduction of the number of TACO and SAAR (Table 3C).

Table 3D: Life-threatening (Grade 3) adverse reactions from transfusion of blood products, TTISS 2009-2013
Type of transfusion-related adverse reaction 2009 2010 2011 2012 2013 Total
Freq. % Freq. % Freq. % Freq. % Freq. % Freq. %
Transfusion-associated circulatory overload (TACO) 0 0.0% 0 0.0% 1 20.0% 2 40.0% 0 0.0% 3 18.8%
Acute hemolytic reaction (AHR) 0 0.0% 0 0.0% 0 0.0% 1 20.0% 0 0.0% 1 6.3%
Severe anaphylactic & anaphylactoid reactions (SAAR) 1 100% 1 25.0% 1 20.0% 0 0.0% 0 0.0% 3 18.8%
Delayed hemolytic reaction (DHR) 0 0.0% 1 25.0% 0 0.0% 0 0.0% 0 0.0% 1 6.3%
Transfusion-related acute lung injury (TRALI) 0 0.0% 1 25.0% 1 20.0% 0 0.0% 0 0.0% 2 12.5%
Possible TRALI 0 0.0% 0 0.0% 1 20.0% 0 0.0% 0 0.0% 1 6.3%
Transfusion-associated dyspnea (TAD) 0 0.0% 0 0.0% 0 0.0% 1 20.0% 0 0.0% 1 6.3%
Other 0 0.0% 1 25.0% 1 20.0% 1 20.0% 1 100% 4 25.0%
Total 1 100% 4 100% 5 100% 5 100% 1 100% 16 100%

Life-threatening adverse reactions from the transfusion of blood products has been consistently limited to not more than five cases per year with 2009 and 2013 recording the lowest (n = 1) number of cases (Table 3D).

4. Rate of occurrence of adverse transfusion-related reactions

Rates of occurrence of adverse reactions could be calculated only for cases that arose from the transfusion of blood components. Cases from the transfusion of blood products could not be considered because of the non-availability appropriate denominator data. Table 4 summarizes the number of units of blood components transfused from 2009 to 2013 by each Canadian jurisdiction participating in the program and corresponding to the denominators in the calculation of the different occurrence rates.

Table 4: Total units of blood components transfused by hospitals of the TTISS network from 2009 to 2013
PROVINCE/Territory 2009 2010 2011 2012 2013
Freq. % within P/T Freq. % within P/T Freq. % within P/T Freq. % within P/T Freq. % within P/T
British Columbia 173,993 96.0% 172,696 96.8% 177,387 96.9% 177,299 98.0% 180,184 98.8%
Yukon Territory 590 100% 551 100% 499 100% 422 100% 809 100%
Alberta 68,561 49.4% 71,978 52.8% 114,734 83.9% 155,120 100% 140,153 95.7%
Manitoba 52,525 100% 55,317 100% 54,819 100% 59,893 100% 56,501 100%
Saskatchewan 56,082 99.7% 51,700 100% 48,182 100% 46,707 100% 42,450 100%
Ontario 351,611 64.5% 349,176 65.3% 378,422 67.0% 365,591 67.5% 357,568 66.9%
Québec 338,005 93.9% 305,220 84.1% 310,047 89.2% 346,565 99.8% 325,995 98.6%
New Brunswick 29,973 100% 31,242 100% 29,276 100% 32,597 100% 30,057 100%
Nova Scotia 39,965 100% 40,646 100% 42,893 100% 43,205 100% 37,685 100%
Prince Edward Island 4,736 100% 4,430 100% 4,607 100% 4,400 100% 4,378 100%
Newfoundland & Labrador 20,556 100% 23,549 100% 23,464 100% 23,856 100% 22,254 100%
Northwest Territories 440 100% 393 100% 348 100% 505 100% 125 100%
Total 1,137,037 79.5% 1,106,898 77.9% 1,184,678 82.5% 1,256,160 87.4% 1,198,159 86.3%

The number of units of blood components transfused annually had not changed significantly over the years (Table 4). Larger proportions were transfused in larger jurisdictions like Québec and Ontario. Though a voluntary system, data on the volume of blood components transfused indicate that the TTISS network had 100% coverage of transfusion activities in eight of the 12 participating Canadian jurisdictions from 2009 to 2013, between 96 and 99% in three other jurisdictions and 67% in one (Table 4).

Figure 1: Annual rate of adverse reactions related to transfusion of blood components, TTISS 2009-2013

Figure 1
Figure 1 - Text Description
Figure 1: Annual rate of adverse reactions related to transfusion of blood components, TTISS 2009-2013
Year TACO SAAR DHR Possible TRALI Incompatible Transfusion Unusual Reactions AHR HR TRALI TAD Bacterial Infection
2009 12.4 4.4 3.3 0.8 0.6 0.8 1.2 3.0 0.7 1.4 0.4
2010 16.7 7.1 2.8 1.3 0.5 1.2 1.4 3.6 0.6 3.1 0.6
2011 18.2 3.9 3.1 0.7 0.7 0.7 1.3 2.5 1.0 1.5 0.8
2012 16.6 5.2 3.0 1.0 0.8 1.9 1.1 5.0 0.6 1.6 0.2
2013 20.2 8.8 3.3 0.7 0.3 0.0 1.4 4.0 0.3 3.8 0.0

The overall risk presented was calculated by dividing the number of adverse reactions from blood components (Table1B) by the total number of units of blood components transfused by hospitals participating in the TTISS from 2009 to 2013 (Table 4). Results are given in number of adverse reactions per 100,000 units of blood components transfused and, the most common has been transfusion-associated circulatory overload (TACO) which consistently posted highest annual rates ranging from 12.4 to 20.2 cases per 100,000 units of blood components transfused. Bacterial contamination has been the least common with an annual rate ranging from zero (in 2013) to 0.8 (in 2011) cases per 100,000 units of blood components transfused

The overall risk presented in Table 5 and Figure 1 was calculated by dividing the number of adverse reactions from blood components (Table1B) by the total number of units of blood components transfused by hospitals participating in the TTISS from 2009 to 2013 (Table 4). The results are given in: (i) adverse reaction per 100,000 units of blood components transfused and (ii) number of units transfused for the occurrence of an adverse event (Tables 5 and Figure 1).

Table 5: Annual rate of adverse reactions related to transfusion of blood components, TTISS 2009-2013
Type of transfusion-related adverse reaction 2009 2010 2011 2012 2013 Total
Per
100,000 UTTable 5 - Footnote 1
1 case per
XTable 5 - Footnote 2 units transfused
Per
100,000 units transfused
1 case per
X units transfused
Per
100,000 units transfused
1 case per
X units transfused
Per
100,000 units transfused
1 case per
X units transfused
Per
100,000 units transfused
1 case per
X units transfused
Per
100,000 units transfused
1 case per
X units transfused
Transfusion-associated circulatory overload (TACO) 12.4 1 : 8,064 16.7 1 : 5,983 18.2 1 : 5,485 16.6 1 : 6,010 20.3 1 : 4,931 16.9 1 : 5,918
Acute hemolytic reaction (AHR) 1.2 1 : 81,218 1.4 1 : 69,181 1.3 1 : 78,979 1.1 1 : 89,726 1.4 1 : 70,480 1.3 1 : 77,407
Severe anaphylactic & anaphylactoid reactions (SAAR) 4.4 1 : 22,741 7.1 1 : 14,011 3.9 1 : 25,754 5.2 1 : 19,326 8.8 1 : 11,303 5.9 1 : 17,003
Hypotensive reaction (HR) 3.0 1 : 33,442 3.6 1 : 27,672 2.5 1 : 39,480 5.0 1 : 19,939 4.1 1 : 24,452 3.7 1 : 27,236
Delayed hemolytic reaction (DHR) 3.3 1 : 29,922 2.8 1 : 35,706 3.1 1 : 32,018 3.0 1 : 33,057 3.4 1 : 29,223 3.1 1 : 31,800
Transfusion-related acute lung injury (TRALI) 0.7 1 : 142,130 0.6 1 : 158,128 1.0 1 : 98,723 0.6 1 : 157,020 0.3 1 : 399,386 0.6 1 : 154,814
Possible TRALI 0.8 1 : 126,337 1.3 1 : 79,064 0.7 1 : 148,085 1.0 1 : 96,628 0.7 1 : 149,770 0.9 1 : 113,133
Transfusion-associated dyspnea (TAD) 1.4 1 : 71,065 3.1 1 : 32,556 1.5 1 : 65,185 1.6 1 : 62,808 3.9 1 : 25,493 2.3 1 : 43,577
Incompatible transfusion 0.6 1 : 162,434 0.5 1 : 184,483 0.7 1 : 148,085 0.8 1 : 125,616 0.3 1 : 399,386 0.6 1 : 173,027
Bacterial infection 0.4 1 : 284,259 0.6 1 : 158,128 0.8 1 : 131,631 0.2 1 : 418,720 0.0 - 0.4 1 : 255,780
Other 0.6 1 : 162,434 1.9 1 : 52,709 3.3 1 : 30,376 2.9 1 : 34,893 4.4 1 : 22,607 2.6 1 : 37,711
Unusual reactions 0.8 1 : 126,337 1.2 1 : 85,146 0.7 1 : 148,085 2.0 1 : 50,246 0.0 - 0.9 1 : 106,962
Total 29.6 1 : 3,374 40.9 1 : 2,443 37.6 1 : 2,656 40.1 1 : 2,492 47.6 1 : 2,102 39.1 1 : 2,547

Overall, the most common adverse transfusion reaction has consistently been transfusion-associated circulatory overload (TACO) which on average occurred once every 5,923 units of blood components transfused (Table 5). Moreover, from 2009 to 2013, there has been a significant 63% increase in its rate of occurrence (Figure 1). The least common was bacterial infection with just 22 cases in four years and no bacterial infection in 2013 (Table 5 & Figure 1).

5. Outcome of reported adverse transfusion-related reactions

Table 6A: Outcome of adverse reactions that resulted from transfusion of blood components, TTISS 2009-2013
Type of transfusion-related adverse reaction Minor sequelaeTable 6 - Footnote 1 Major sequelaeTable 6 - Footnote 2 Death Not determinedTable 6 - Footnote 3 Total
Freq. % Freq. % Freq. % Freq. % Freq. %
Transfusion-associated circulatory overload (TACO) 913 44.3% 12 19.4% 14 35.0% 52 40.3% 991 43.1%
Acute hemolytic reaction (AHR) 59 2.9% 7 11.3% 1 2.5% 9 7.0% 76 3.3%
Severe anaphylactic & anaphylactoid reactions (SAAR) 321 15.5% 8 12.9% 1 2.5% 14 10.9% 344 15.0%
Hypotensive reaction (HR) 205 9.9% 2 3.2% 0 0.0% 6 4.7% 213 9.3%
Delayed hemolytic reaction (DHR) 148 7.2% 19 30.6% 3 7.5% 15 10.9% 185 8.0%
Transfusion-related acute lung injury (TRALI) 32 1.6% 0 0.0% 3 7.5% 3 2.3% 38 1.7%
Possible TRALI 27 1.3% 6 9.7% 13 32.5% 6 4.7% 52 2.3%
Transfusion-associated dyspnea – TAD 121 5.8% 4 6.5% 1 2.5% 7 5.4% 133 5.8%
Incompatible transfusion 29 1.4% 0 0.0% 1 2.5% 4 3.1% 34 1.5%
Bacterial infection 18 0.8% 0 0.0% 1 2.5% 4 3.1% 23 1.0%
Other 146 7.0% 0 0.0% 2 5.0% 7 5.4% 155 6.7%
Unusual reactions 48 2.3% 4 6.5% 0 0.0% 3 2.3% 55 2.4%
Total 2,067 100% 62 100% 40 100% 130 100% 2,299 100%

N.B.: The sum total from Tables 6A & 6B does not match that of Table 1A because of missing outcome information on 19 cases.

More than two percent (2.3%, n=77) of the cases with outcome information developed either a serious infection or a transfusion reaction with major /long-term sequelae (Tables 6A & 6B). Approximately 64.3% of the 42 deaths recorded in the TTISS network between 2009 and 2013 were determined to be either definitely (n=3), probably (n=9) or possibly (n=15) related to the adverse events that resulted from the transfusion of blood components (Table 7). Such linkage for the 15 other cases was either ruled out (n=6) or at best doubtful (n=9).

Table 6B: Outcome of adverse reactions that resulted from transfusion of blood products (plasma derivatives), TTISS 2009- 2013
Type of transfusion-related adverse reaction Minor sequelae Major sequelae Death Not determined Total
Freq. % Freq. % Freq. % Freq. % Freq. %
Transfusion-associated circulatory overload (TACO) 41 4.1% 0 0.0% 1 50.0% 1 3.3% 43 4.1%
Acute hemolytic reaction (AHR) 77 7.7% 1 6.7% 0 0.0% 7 23.3% 85 8.1%
Severe anaphylactic & anaphylactoid reactions (SAAR) 79 7.9% 1 6.7% 0 0.0% 4 13.3% 84 8.0%
Hypotensive reaction (HR) 28 2.8% 0 0.0% 0 0.0% 1 3.3% 29 2.8%
Delayed hemolytic reaction (DHR) 165 16.5% 5 33.3% 0 0.0% 7 23.3% 177 16.9%
Transfusion-related acute lung injury (TRALI) 3 0.3% 0 0.0% 0 0.0% 1 3.3% 4 0.4%
Possible TRALI 1 0.1% 0 0.0% 0 0.0% 0 0.0% 1 0.1%
Transfusion-associated dyspnea – TAD 28 2.8% 1 6.7% 0 0.0% 0 0.0% 29 2.8%
IVIG-associated reaction 363 36.2% 1 6.7% 0 0.0% 2 6.7% 366 34.9%
Aseptic meningitis 39 3.9% 1 6.7% 0 0.0% 2 6.7% 42 4.0%
Incompatible transfusion 3 0.3% 0 0.0% 0 0.0% 0 0.0% 3 0.3%
Other 166 16.5% 5 33.3% 1 50.0% 5 16.7% 177 16.9%
Unusual reactions 10 1.0% 0 0.0% 0 0.0% 0 0.0% 10 1.0%
Total 1,003 100% 15 100% 2 100% 30 100% 1,050 100%

The two cases of death registered among patients transfused with plasma derivatives (Table 6B) were determined not to be linked to transfusion. Fifteen (1.4%) of the recipients of plasma derivatives sustained major (or long-term) sequelae and of these, five had been diagnosed with transfusion-related delayed hemolytic reaction (Table 6B).

Table 7: Strength of the relationship between adverse transfusion reaction and death, TTISS 2009 – 2013
Transfusion-related death DefiniteTable 7 - Footnote 1 ProbableTable 7 - Footnote 2 PossibleTable 7 - Footnote 3 DoubtfulTable 7 - Footnote 4 Ruled outTable 7 - Footnote 5 Total
Transfusion-associated circulatory overload  (TACO) 0 2 5 5 3 15
Acute hemolytic reaction (AHR) - (incompatible transfusion) 1 0 0 0 0 1
Severe anaphylactic & anaphylactoid reactions (SAAR) 0 0 0 0 1 1
Delayed hemolytic reaction (DHR) 0 0 1 1 1 3
Transfusion-related acute lung injury (TRALI) 1 1 1 0 0 3
Possible TRALI 0 5 6 2 0 13
Transfusion-associated dyspnea – TAD 0 0 0 1 0 1
Incompatible transfusions 0 0 0 0 1 1
Bacterial infection 0 0 1 0 0 1
Other 1 1 1 0 0 3
Total 3 9 15 9 6 42

More than 81% of the cases of death were patients diagnosed either with TRALI and possible TRALI (51.9%) or TACO (29.5%) as per Table 8.

Table 8: Trend of definite, probable and possible transfusion-related deaths recorded in the TTISS network from 2009 to 2013
Transfusion-related death 2009 2010 2011 2012 2013 Total
Transfusion-associated circulatory overload (TACO) 1 1 1 2 1 6
Acute hemolytic reaction (AHR) - (incompatible transfusion) 0 0 0 0 1 1
Delayed hemolytic reaction (DHR) 0 0 0 0 1 1
Transfusion-related acute lung injury (TRALI) 0 1 1 1 0 3
Possible TRALI 2 3 2 2 2 11
Bacterial infection 0 0 1 0 1 2
Incompatible transfusion 0 0 0 0 1 1
Other 1 0 0 1 0 2
Total 4 5 5 6 7 27

Among the 2013 six transfusion-related deaths (Table 8), the relationship with transfusion was definite in two cases (incompatible transfusion and bacterial contamination), probable in one case (delayed hemolytic reaction), and possible in three cases (two cases of possible TRALI and one case of TACO). Definite transfusion-related cases occurred in males of 78 and 71 years of age unintentionally transfused respectively with blood of wrong type (B+ red blood cell to an A+ recipient) and apheresed platelets contaminated with alpha-hemolytic streptococcus. The first was admitted with community-acquired pneumonia and sepsis and as a result of incompatible transfusion developed a fatal acute hemolytic reaction, whereas the second who failed to recover from the transfusion of bacterially contaminated apheresed platelets was diagnosed with pancytopenia and had been hospitalized for over 30 days. The probable transfusion-related case was an 81 year old female victim of a motor vehicle accident with multiple injuries and significantly bleeding who expired on the same day following massive transfusion. Cases of death deemed to be possibly related to transfusion included: (i) a 56 year old female with relapsed acute myeloid leukemia on palliative chemotherapy who developed a possible TRALI following platelets transfusion, and (ii) a 75 year old diagnosed with idiopathic/ warm autoimmune hemolytic anemia who was transfused with red blood cells and IVIG and as a result developed a fatal hyper hemolysis coupled with severe multiple system dysfunction.

Acknowledgments: The development of the Transfusion Transmitted Surveillance System (TTISS) would not have been possible without the collaborative support and continued commitment of the provincial/territorial Blood Coordinating Offices, transfusion medicine staff at participating hospitals, the Canadian Blood Services and Héma-Quebec. Their dedication to reducing adverse transfusion reactions/injuries and increasing patient safety has led to the collection and analysis of the 2009-2013 TTISS data.

N.B. This document must be cited as the source for any information extracted and used from it.

Suggested citation: Public Health Agency of Canada. Transfusion Transmitted Injuries Surveillance System (TTISS):  2009-2013 Summary Results. Centre for Communicable Diseases and Infection Control, Public Health Agency of Canada, 2016.

Centre for Communicable Diseases and Infection Control
Public Health Agency of Canada
130 Colonnade, AL 06503B
Ottawa, Ontario, K1A 0K9
E-mail: ccdic-clmti@phac-aspc.gc.ca

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