Vox Sanguinis (2015) 109, 197–200 © 2015 International Society of Blood Transfusion DOI: 10.1111/vox.12262
SHORT REPORT
Transfusion-associated dyspnoea – shadow or substance? K. G. Badami,1 E. Joliffe2 & M. Stephens2 1
New Zealand Blood Service, Christchurch, New Zealand New Zealand Blood Service, Wellington, New Zealand
2
Received: 11 September 2014, revised 26 January 2015, accepted 27 January 2015, published online 8 April 2015
New Zealand Blood Service Haemovigilance uses International Society of Blood Transfusion/International Haemovigilance Network definitions to categorize transfusion reactions (TR). Transfusion-associated dyspnoea (TAD) is a category for TR with respiratory features (TRRF) that do not fit definitive entities. TRRF, including TAD, are clinically significant. TR classified as TAD were reviewed. We found that many TAD may have been transfusion-associated circulatory overload. Better information in TR reports and refining TR diagnostic criteria may result in less misclassification of TRRF. TAD may represent mild, atypical or overlap entities, and there may be a residuum of cases with currently unexplained pathophysiology. Key words: transfusion, dyspnoea, heart failure.
Introduction A minority of transfusion reactions (TR) are associated with respiratory features (TRRF), but these are among the most serious [1, 2]. Included in this category are transfusion-associated acute heart failure (HF) or acutely decompensated chronic HF (referred to in transfusion medicine literature as transfusion-associated circulatory overload or TACO) and transfusion-related acute lung injury (TRALI). Severe allergic reactions can also be a TRRF. New Zealand Blood Service (NZBS) Haemovigilance (HV) uses the International Society of Blood Transfusion/International Haemovigilance Network (ISBT/IHN) definitions to classify TR [1]. Some TRRF do not fit ISBT/IHN definitions for TACO, TRALI or allergic reactions. A separate category, transfusion-associated dyspnoea (TAD), which is not a true pathophysiologic entity, has been created for these. TAD is described as ‘respiratory distress within 24 h of transfusion that does not meet the criteria of TRALI, TACO, or allergic reaction. Respiratory distress should be the most prominent clinical feature and should not be explained by the patient’s underlying condition or any other known cause’ [3]. We aimed to see whether our TAD cases were reclassifiable as true pathophysiologic entities using information
Correspondence: Krishna G. Badami, New Zealand Blood Service, 15, Lester Lane, Addington, Christchurch, New Zealand E-mail: [email protected]
in case notes, how information in initial TR reports compared to case notes, whether TAD classifications were increasing, and how TRRF classification in our system compared with others.
Methods Data TR reported on standard forms and classified as TAD by the NZBS HV group between 1 June 2011 and 31 May 2013 were reviewed. Relevant sections of case notes, including results of investigations, and any diagnosis made by the treating team, were obtained. Information relevant to the assessment of TRRF – chest X-ray/other chest imaging, jugular/central venous pressure (JVP/CVP), brain natriuretic peptide (BNP) and fluid balance – was sought in both the TR report and case notes. In addition, data on TR and TRRF were collated from NZBS HV annual reports from 2006 (when the programme was started) to 2012 (the year of the last available report at the time) [1].
Data review Two medical registrars with transfusion medicine experience independently reviewed the TR reports and associated case notes and attempted reclassification using ISBT/ IHN definitions – first, based on initial TR reports and, 197
198 K. G. Badami et al.
then, taking into consideration additional information from the notes. The diagnosis by the treating team was recorded if available.
Statistical analysis Apart from basic descriptive statistics, Cohen’s kappa (j) for inter-rater agreement, a measure of agreement relative to that likely due to chance alone, was calculated (GraphPad Software, Inc., La Jolla, CA, USA).
Results During the study period, 37 TR reports, from 14 hospitals, were classified as TAD. Patient age varied from 4 to 95 years. Twenty-two reports involved females and 15, males. In 31 of 37 TAD events, red cells (RBC) were the sole blood component involved; in 1 of 37 it was RBC and fresh frozen plasma (FFP); in 2 of 37, platelets alone; in 1 of 37, FFP alone; in 1 of 37, platelets and FFP; and in 1 of 37, cryodepleted plasma. Results of
reclassification by the reviewers are summarized in Table 1. In 17 (459%) cases, the treating team had either no diagnosis or considered the event to be non-transfusionrelated. For 13 (351%) cases, the diagnosis was TACO; in 4 (11%), it was a TR that was not a TRRF; and in 3 (8%), it was TAD. We are unaware of the criteria used for these diagnoses or classifications. Also, note that, in our setting, adverse events related to transfusion may be reported even if the treating team considers it not to have been caused by the transfusion. All initial TR reports had information on heart rate, respiratory rate and blood pressure. Information on chest X-ray/other chest imaging, JVP/CVP, BNP and fluid balance was present respectively in 19%, 8%, 11% and 5% of initial TR reports and absent respectively from both initial TR report and case notes in 49%, 57%, 88% and 88%. TR classified as TRRF, including TAD, were recorded by NZBS every year from 2008 to 2012. Data are summarized in Table 2.
Table 1 Reclassification after review of 37 transfusion reactions initially classified as TAD Based on additional information from case notes
Based on TR report Reviewer 1 Reclassification category TAD TACO Transfusion-related other Not transfusion-related/no reaction/no comment N (%) observed agreements N (%) expected agreements Kappa (95% CI) Inter-rater agreement
Reviewer 2
34 33 1 0 2 4 0 0 30 (811) 305 (824) -007 (-013 to -001) Worse than by chance alone
Reviewer 1
Reviewer 2
16 8 3 10 23 (622) 123 (332) 04 (019 to 066) Moderate
15 6 1 15
Table 2 Transfusion reactions classified as TACO, TRALI and TAD in New Zealand Blood Service Haemovigilance, 2008–2012 TACO
TRALI
TAD
Yeara
TR (n)
n
As % of all TR
As % of TRRF
n
As % of all TR
As % of TRRF
n
As % of all TR
As % of TRRF
TRRF as % of TR
2008 2009 2010 2011 2012
447 488 555 442 442
20 24 13 19 27
45 49 23 43 61
69 62 52 68 61
3 1 3 3 2
07 02 05 07 05
10 3 12 11 5
6 14 9 6 15
13 29 16 14 34
21 36 36 21 34
65 80 45 63 99
a Data for 2006 and 2007 not shown as classifications with varying degrees of imputability were recorded. From 2008 onwards, TR with imputability score ≥ 3 are included. The imputability score describes the likelihood that transfusion was the cause of the TR. The ISBT/IHN system has scores from 1 to 5 with higher scores indicating increasing likelihood [3].
© 2015 International Society of Blood Transfusion Vox Sanguinis (2015) 109, 197–200
Review of transfusion-associated dyspnoea 199
Discussion As far as we know, there are no previous published reviews of TAD. TRRF are about 4–10%, and TAD about 1–35%, of all TR in NZBS HV. Reports of TAD and TRRF in other national HV systems are variable, and comparisons are difficult [4–6]. Differences in the definitions used, and the rigour with which they are applied, are possible. In our study, many reported TRRF were likely misclassified (though not per ISBT/IHN definitions). Independent review of TR reports initially categorized as TAD resulted in reclassification of
SHORT REPORT
Transfusion-associated dyspnoea – shadow or substance? K. G. Badami,1 E. Joliffe2 & M. Stephens2 1
New Zealand Blood Service, Christchurch, New Zealand New Zealand Blood Service, Wellington, New Zealand
2
Received: 11 September 2014, revised 26 January 2015, accepted 27 January 2015, published online 8 April 2015
New Zealand Blood Service Haemovigilance uses International Society of Blood Transfusion/International Haemovigilance Network definitions to categorize transfusion reactions (TR). Transfusion-associated dyspnoea (TAD) is a category for TR with respiratory features (TRRF) that do not fit definitive entities. TRRF, including TAD, are clinically significant. TR classified as TAD were reviewed. We found that many TAD may have been transfusion-associated circulatory overload. Better information in TR reports and refining TR diagnostic criteria may result in less misclassification of TRRF. TAD may represent mild, atypical or overlap entities, and there may be a residuum of cases with currently unexplained pathophysiology. Key words: transfusion, dyspnoea, heart failure.
Introduction A minority of transfusion reactions (TR) are associated with respiratory features (TRRF), but these are among the most serious [1, 2]. Included in this category are transfusion-associated acute heart failure (HF) or acutely decompensated chronic HF (referred to in transfusion medicine literature as transfusion-associated circulatory overload or TACO) and transfusion-related acute lung injury (TRALI). Severe allergic reactions can also be a TRRF. New Zealand Blood Service (NZBS) Haemovigilance (HV) uses the International Society of Blood Transfusion/International Haemovigilance Network (ISBT/IHN) definitions to classify TR [1]. Some TRRF do not fit ISBT/IHN definitions for TACO, TRALI or allergic reactions. A separate category, transfusion-associated dyspnoea (TAD), which is not a true pathophysiologic entity, has been created for these. TAD is described as ‘respiratory distress within 24 h of transfusion that does not meet the criteria of TRALI, TACO, or allergic reaction. Respiratory distress should be the most prominent clinical feature and should not be explained by the patient’s underlying condition or any other known cause’ [3]. We aimed to see whether our TAD cases were reclassifiable as true pathophysiologic entities using information
Correspondence: Krishna G. Badami, New Zealand Blood Service, 15, Lester Lane, Addington, Christchurch, New Zealand E-mail: [email protected]
in case notes, how information in initial TR reports compared to case notes, whether TAD classifications were increasing, and how TRRF classification in our system compared with others.
Methods Data TR reported on standard forms and classified as TAD by the NZBS HV group between 1 June 2011 and 31 May 2013 were reviewed. Relevant sections of case notes, including results of investigations, and any diagnosis made by the treating team, were obtained. Information relevant to the assessment of TRRF – chest X-ray/other chest imaging, jugular/central venous pressure (JVP/CVP), brain natriuretic peptide (BNP) and fluid balance – was sought in both the TR report and case notes. In addition, data on TR and TRRF were collated from NZBS HV annual reports from 2006 (when the programme was started) to 2012 (the year of the last available report at the time) [1].
Data review Two medical registrars with transfusion medicine experience independently reviewed the TR reports and associated case notes and attempted reclassification using ISBT/ IHN definitions – first, based on initial TR reports and, 197
198 K. G. Badami et al.
then, taking into consideration additional information from the notes. The diagnosis by the treating team was recorded if available.
Statistical analysis Apart from basic descriptive statistics, Cohen’s kappa (j) for inter-rater agreement, a measure of agreement relative to that likely due to chance alone, was calculated (GraphPad Software, Inc., La Jolla, CA, USA).
Results During the study period, 37 TR reports, from 14 hospitals, were classified as TAD. Patient age varied from 4 to 95 years. Twenty-two reports involved females and 15, males. In 31 of 37 TAD events, red cells (RBC) were the sole blood component involved; in 1 of 37 it was RBC and fresh frozen plasma (FFP); in 2 of 37, platelets alone; in 1 of 37, FFP alone; in 1 of 37, platelets and FFP; and in 1 of 37, cryodepleted plasma. Results of
reclassification by the reviewers are summarized in Table 1. In 17 (459%) cases, the treating team had either no diagnosis or considered the event to be non-transfusionrelated. For 13 (351%) cases, the diagnosis was TACO; in 4 (11%), it was a TR that was not a TRRF; and in 3 (8%), it was TAD. We are unaware of the criteria used for these diagnoses or classifications. Also, note that, in our setting, adverse events related to transfusion may be reported even if the treating team considers it not to have been caused by the transfusion. All initial TR reports had information on heart rate, respiratory rate and blood pressure. Information on chest X-ray/other chest imaging, JVP/CVP, BNP and fluid balance was present respectively in 19%, 8%, 11% and 5% of initial TR reports and absent respectively from both initial TR report and case notes in 49%, 57%, 88% and 88%. TR classified as TRRF, including TAD, were recorded by NZBS every year from 2008 to 2012. Data are summarized in Table 2.
Table 1 Reclassification after review of 37 transfusion reactions initially classified as TAD Based on additional information from case notes
Based on TR report Reviewer 1 Reclassification category TAD TACO Transfusion-related other Not transfusion-related/no reaction/no comment N (%) observed agreements N (%) expected agreements Kappa (95% CI) Inter-rater agreement
Reviewer 2
34 33 1 0 2 4 0 0 30 (811) 305 (824) -007 (-013 to -001) Worse than by chance alone
Reviewer 1
Reviewer 2
16 8 3 10 23 (622) 123 (332) 04 (019 to 066) Moderate
15 6 1 15
Table 2 Transfusion reactions classified as TACO, TRALI and TAD in New Zealand Blood Service Haemovigilance, 2008–2012 TACO
TRALI
TAD
Yeara
TR (n)
n
As % of all TR
As % of TRRF
n
As % of all TR
As % of TRRF
n
As % of all TR
As % of TRRF
TRRF as % of TR
2008 2009 2010 2011 2012
447 488 555 442 442
20 24 13 19 27
45 49 23 43 61
69 62 52 68 61
3 1 3 3 2
07 02 05 07 05
10 3 12 11 5
6 14 9 6 15
13 29 16 14 34
21 36 36 21 34
65 80 45 63 99
a Data for 2006 and 2007 not shown as classifications with varying degrees of imputability were recorded. From 2008 onwards, TR with imputability score ≥ 3 are included. The imputability score describes the likelihood that transfusion was the cause of the TR. The ISBT/IHN system has scores from 1 to 5 with higher scores indicating increasing likelihood [3].
© 2015 International Society of Blood Transfusion Vox Sanguinis (2015) 109, 197–200
Review of transfusion-associated dyspnoea 199
Discussion As far as we know, there are no previous published reviews of TAD. TRRF are about 4–10%, and TAD about 1–35%, of all TR in NZBS HV. Reports of TAD and TRRF in other national HV systems are variable, and comparisons are difficult [4–6]. Differences in the definitions used, and the rigour with which they are applied, are possible. In our study, many reported TRRF were likely misclassified (though not per ISBT/IHN definitions). Independent review of TR reports initially categorized as TAD resulted in reclassification of
