Vaccines, Blood & Biologics
Resources for You
Fatalities Reported to FDA Following Blood Collection and Transfusion: Annual Summary for Fiscal Year 2012
Due to new data, report was updated 03/28/2014.
As previously mentioned in the annual summary of fatalities reported to the FDA in Fiscal Years (FY) 2005 through FY2011, the blood supply is safer today than at any time in history. Due to advances in donor screening, improved testing, automated data systems, and changes in transfusion medicine practices, the risks associated with blood transfusion continue to decrease. Overall, the number of transfusion related fatalities reported to the FDA remains small in comparison to the total number of transfusions. In 2008, for example, there were approximately 24 million blood components transfused.1 During the proximate period of FY2008, there were 54 reported transfusion related and potentially2 transfusion related fatalities, with subsequent reports of 66 in FY2009, 64 in FY2010, 58 in FY2011, and 65 in FY2012.
CBER is distributing this summary of transfusion fatality reports received by the FDA to make public the data received in FY2012, to provide the combined data received over the last five fiscal years, and to compare the FY2012 report to the fatality reports received in the previous four fiscal years.3 We also include information on the infrequent reports of post-donation fatalities. Throughout this report we note changes over time, but the reader should interpret these changes cautiously, given the small numbers of reports and inherent variations in reporting accuracy. The significance of shifts in numbers derived from small populations may appear to be greater than they really are.
Refer to Sections 606.170(b) and 640.73 of Title 21, Code of Federal Regulations (21 CFR 606.170(b) and 21 CFR 640.73), for fatality reporting requirements. For information regarding the notification process, see our web page, Notification Process for Transfusion Related Fatalities and Donation Related Deaths. For further information, see our Guidance for Industry: Notifying FDA of Fatalities Related to Blood Collection or Transfusion, September 2003.4
A team of CBER medical officers reviews the documentation submitted by the reporting facilities and obtained by FDA investigators, to assess the relationship, if any, between the blood donation or transfusion and the reported fatality.
If you have questions concerning this summary, you may contact us using any of the three following options:
- Email us at email@example.com,
- Call us at 301-827-6220, or
- Write us at:
FDA/Center for Biologics Evaluation and Research
Office of Compliance and Biologics Quality
Division of Inspections and Surveillance (HFM-650)
1401 Rockville Pike, Suite 200 North
Rockville, Maryland 20852-1448
During FY2012 (October 1, 2011, through September 30, 2012), we received a total of 88 fatality reports. Of these reports, 74 were transfusion recipient fatalities and 14 were post-donation fatalities.
Of the 74 transfusion recipient fatality reports, we concluded:
- 38 (51%) of the fatalities were transfusion-related,
- 27 (36%) of the fatalities were cases in which transfusion could not be ruled out as the cause of the fatality,
- 9 (12%) of the fatalities were unrelated to the transfusion.
Of the 14 post-donation fatality reports, we concluded:
- 11 of the fatalities were cases in which donation could not be ruled out as the cause of the fatality,
- 3 of the fatalities were unrelated to the donation.
We summarize the results of our review in the following sections. Sections A through D of this document present the transfusion-related fatalities. Sections E and F and Table 4 present the fatality reports which were unrelated to the transfusion, or in which we could not rule out the transfusion as the cause of death. Section G presents the post-donation fatality reports.
A. Overall Comparison of Transfusion-Related Fatalities Reported from FY2008 through FY2012
B. Transfusion Related Acute Lung Injury (TRALI)
C. Hemolytic Transfusion Reactions (HTR)
D. Microbial Infection
E. Transfusion Not Ruled Out as Cause of Fatality
F. Not Transfusion Related
G. Post-Donation Fatalities
In combined Fiscal Years 2008 through 2012, Transfusion Related Acute Lung Injury (TRALI) caused the highest number of reported fatalities (37%), followed by hemolytic transfusion reactions (total of 27%) due to non-ABO (16%) and ABO (11%) incompatibilities. Complications of Transfusion Associated Circulatory Overload (TACO) (18%), microbial infection (11%), and anaphylactic reactions (6%) each accounted for a smaller number of reported fatalities (Table 1 and Figure 1). The number of fatalities attributed to TACO has varied over the reporting period, with no noted trend. Recent articles provide additional information about TACO. 5,6,7 The number of reported transfusion related deaths attributable to anaphylaxis8,9 has remained small over the last five fiscal years. With the exception of one FY2010 case, in which IgA levels were not measured, patient IgA deficiency was ruled out in 11 of the 12 cumulatively reported cases. In another FY2010 case, a haptoglobin deficiency was possibly implicated in the patient’s anaphylactic reaction.
Table 1: Transfusion-Related Fatalities by Complication, FY2008 through FY2012 Complication FY08 FY08 FY09 FY09 FY10 FY10 FY11 FY11 FY12 FY12 Total Total No. % No. % No. % No. % No. % No. % TRALI* 16 35% 13 30% 18 45% 10 33% 17 45% 74 37% HTR (non-ABO) 7 15% 8 18% 5 13% 6 20% 5 13% 31 16% HTR (ABO) 10 22% 4 9% 2 5% 3 10% 3 8% 22 11% Microbial Infection 7 15% 5 11% 2 5% 4 12% 3 8% 21 11% TACO 3 7% 12 27% 8 20% 4 13% 8 21% 35 18% Anaphylaxis 3 7% 1 2% 4 10% 2 7% 2 5% 12 6% Other 0 0% 1** 2% 1** 3% 1** 3% 0 0% 3 1% Totals 46 100% 44 100% 40 100% 30 100% 38 100% 198 100% *These numbers include both “TRALI” and “possible TRALI” cases10,11 **Other:
FY2009: Hypotensive Reaction12
FY2010: Graft vs. Host Disease (GVHD)
Figure 1: Transfusion-Related Fatalities by Complication, FY2008 through FY2012
TRALI represented 37% of confirmed transfusion related fatalities reported to CBER over the last five fiscal years. There was an increase in TRALI fatalities, from 10 (33% of confirmed transfusion related fatalities) in FY2011, to 17 (45%) in FY2012 (Table 1 and Figure 1). However, the TRALI fatalities in FY2008 (16/46 or 35%) represented a decrease from FY2007 when the number of confirmed transfusion-related TRALI fatalities was 34/52 or 65%. Following this decrease, the total number of TRALI fatalities, as well as the number of TRALI fatalities associated with plasma products, has remained relatively unchanged over the reporting period FY2008 - FY2012 (Figure 2 and Figure 3).
In FY2012, the 17 TRALI cases were temporally associated with products collected from 39 donors. Genders were identified for 30 of the donors, which included 18 males and 12 females. HLA/HNA antibody test results were available for 17 of these donors.
In four of the 17 FY2012 TRALI cases, reporters who included patient testing data were able to match donor antibodies with recipient cognate antigens.
Our limited data do not elucidate the role of particular donor antibodies or donor gender in the etiology of the TRALI reactions.
Although this complication of transfusion continues to be one of the leading causes of transfusion-related fatalities reported to the FDA, the voluntary measures taken by the transfusion community to reduce the risk of TRALI have coincided with a reduction in the number of TRALI deaths. Current literature describes the results of continued international efforts to reduce the use of plasma for transfusion prepared from female donors, and other strategies to reduce the incidence of TRALI.13,14,15,16,17,18,19,20
Figure 2: TRALI Cases, FY2002 through FY2012
FY02:14; FY03:19; FY04:21; FY05:29; FY06:35; FY07:34; FY08-16; FY09:13; FY10:18; FY11:10; FY12:17
Figure 3: Reports of TRALI Cases by Implicated Blood Product, FY2008 through FY2012
FY08:FFP:4;RBC:5;FP24:0;Platelets Pheresis:5;Pooled Platelets:0;Multiple Products:2
FY09:FFP:2;RBC:6;FP24:1;Platelets Pheresis:2;Pooled Platelets:0;Multiple Products:2
FY10:FFP:4;RBC:8;FP24:0;Platelets Pheresis:1;Pooled Platelets:1;Multiple Products:4
FY11:FFP:3;RBC:3;FP24:1;Platelets Pheresis:2;Pooled Platelets:0;Multiple Products:1
FY12:FFP:0;RBC:6;FP24:2;Platelets Pheresis:5;Pooled Platelets:0;Multiple Products:4
In FY2012, the number of reported fatal hemolytic transfusion reactions was relatively unchanged in comparison to the number reported in FY2011 (Tables 1 and 2, and Figure 1). The downward trend in the total number of reported fatalities due to hemolytic transfusion reactions has continued since FY2001 (Figure 4).
Table 2: Hemolytic Transfusion Reactions by Implicated Antibody, FY2008 through FY2012 Antibody FY08 FY08 FY09 FY09 FY10 FY10 FY11 FY11 FY12 FY12 Total Total No. % No. % No. % No. % No. % No. % ABO 10 59% 4 33% 2 29% 3 33% 3 38% 22 42% Multiple Antibodies* 1 6% 2 17% 3 43% 1 11% 2 25% 9 17% Other** 0 0% 2 17% 0 0% 2 22% 0 0% 4 7% Fya 2 12% 1 8% 0 0% 1 11% 0 0% 4 7% Jkb 2 12% 0 0% 1 14% 0 0% 1 13% 4 7% Kell 2 12% 0 0% 0 0% 1 11% 1 13% 4 7% Jka 0 0% 2 17% 0 0% 0 0% 0 0% 2 4% c 0 0% 0 0% 0 0% 1 11% 0 0% 1 2% Jsb 0 0% 1 8% 0 0% 0 0% 1 13% 2 4% Coa 0 0% 0 0% 1 14% 0 0% 0 0% 1 2% Totals 17 100% 12 100% 7 100% 9 100% 8 100% 53 100% *Multiple Antibodies:
FY2008: anti-C+K+Fyb+S+N+V+Jsa+Goa+warm autoantibody.
FY2009: antibody combinations included E+Jkb, S+Jka+Jkb+K+Fya+Fyb+V+C+N+HTLA.
FY2010: antibody combinations included D+C+K+S, Jkb+FYa+C+E+K+Lea+Leb, c+E+Jkb+K+Lea+panagglutinin+cold agglutinin.
FY2011: anti-Jka+c+E+M (warm reacting).
FY2012: antibody combinations included S+E, C+K.
FY2009: Includes one report of an unidentified warm autoantibody, and one report of Hyperhemolysis Syndrome. Information about this syndrome has been published.21
FY2011: Includes one report of Hyperhemolysis Syndrome, and one report of an unidentified antibody.
Figure 4: Hemolytic Transfusion Reactions, FY2001 through FY2012
FY01:23; FY02:28; FY03:18; FY04:14; FY05:22; FY06:12; FY07:5; FY08:17; FY09:12; FY10:7; FY11:9; FY12:7
In FY2012, there were three reports of fatal hemolytic transfusion reactions due to ABO-incompatible transfusions:
Two of these fatalities were attributed to errors:
- In one case, a phlebotomist collected extra specimens for two patients, anticipating future crossmatch orders for both. The extra specimens were correctly labeled. After receiving crossmatch orders, the phlebotomist switched the specimens and applied the blood bank labels over the existing labels, prior to delivering the specimens to the Blood Bank. As a result, the incorrect blood groups were assigned to both patients, and the group O patient was transfused with an incompatible group A Red Blood Cell (RBC) unit.
- In the second case, a group AB RBC unit, which was correctly labeled for the intended patient, was issued to the Emergency Room (ER), and transfused to a group A patient, who was also in the ER. This error occurred due to failure of ER personnel to properly identify the patient prior to transfusion.
The remaining case illustrates the potential risk associated with ABO-incompatible plasma in plateletpheresis products, when donor ABO antibodies in the transfusion product are incompatible with the patient’s red blood cells and are present in sufficiently high titers to cause in vivo hemolysis.22 This case involved transfusion from two group O donors with high-titers of anti-A. Over the last five years there have been two other fatalities due to transfusion of group O apheresis platelets with high-titer blood group antibodies, an anti-A (FY2011) and an anti-B (FY2008). In both of these earlier cases, the recipient’s blood group had recently changed following ABO-mismatched hematopoietic stem cell transplants.
In FY2012, there were five reports of non-ABO fatal hemolytic transfusion reactions:
One of the five cases was attributed to a laboratory error. In this case, a positive antibody screen misread as negative resulted in transfusion of three units of incompatible E and/or S positive RBC units. The immediate spin compatibility tests did not detect the incompatibilities. Additionally, the patient’s prior records containing the antibody information were misfiled. Records were maintained in a manual record-keeping system.
Two of the remaining four cases involved delayed hemolytic transfusion reactions in patients whose pre-existing antibodies were undetectable prior to transfusion.
The remaining two cases involved emergent transfusions of uncrossmatched RBC units to patients with known pre-existing antibodies. In both cases, there was insufficient time to phenotype units for the corresponding antigens, or to wait for delivery of antigen-negative units from an outside source.
In FY2012, there were three reported fatalities attributed to microbial infection, compared to four in FY2011. Babesia microti, associated with a transfusion of Red Blood Cells, was implicated in one of these fatalities, and Staphylococcus aureus and Serratia marcescens were implicated, one case each, in platelet transfusion fatalities. Specifically, Apheresis Platelets were associated with the S. aureus infection, and the S. marcescens infection was associated with a unit of Pooled Platelets (Figure 5).
Babesia accounts for 38% (8/21) of reported deaths due to microbial infection over the previous five fiscal years, followed by S. aureus, which accounts for 24% (5/21) (Table 3).
During the five-year reporting period, all of the implicated bacteria associated with fatal microbial infections were facultative anaerobes.
Figure 6 shows a downward trend in the number of bacterial infections associated with Apheresis Platelets since FY2001.
Table 3: Microbial Infection by Implicated Organism, FY2008 through FY2012 Organism FY08 FY08 FY09 FY09 FY10 FY10 FY11 FY11 FY12 FY12 Total Total No. % No. % No. % No. % No. % No. % Babesia* 5 71% 0 0% 1 50% 1 25% 1 33% 8 38% Staphylococcus aureus 1 14% 2 40% 0 0% 1 25% 1 33% 5 24% Escherichia coli 0 0% 0 0% 1 50% 0 0% 0 0% 1 5% Staphylococcus epidermidis 1 14% 0 0% 0 0% 0 0% 0 0% 1 5% Morganella morganii 0 0% 0 0% 0 0% 1 25% 0 0% 1 5% Streptococcus viridans 0 0% 1 20% 0 0% 0 0% 0 0% 1 5% Streptococcus pneumoniae 0 0% 1 20% 0 0% 0 0% 0 0% 1 5% Staphylococcus warneri 0 0% 1 20% 0 0% 0 0% 0 0% 1 5% Klebsiella pneumoniae 0 0% 0 0% 0 0% 1 25% 0 0% 1 5% Serratia marcescens 0 0% 0 0% 0 0% 0 0% 1 33% 1 5% Total 7 100% 5 100% 2 100% 4 100% 3 100% 21 100%
*Seven Babesia microti and one probable Babesia MO-1 species (FY2008)
Figure 5: Microbial Infection by Implicated Blood Product, FY2008 through FY2012
FY08:RBC:5;Pooled Platelets:0;Platelets Pheresis:2
FY09:RBC:0;Pooled Platelets:1;Platelets Pheresis:4
FY10:RBC:1;Pooled Platelets:1;Platelets Pheresis:0
FY11:RBC:1;Pooled Platelets:1;Platelets Pheresis:2
FY12:RBC:1;Pooled Platelets:1;Platelets Pheresis:1
Red Blood Cells microorganisms: B. microti (7), B. MO1(1)
Pooled Platelets microorganisms: S. aureus (1), E. coli (1), S. pneumoniae (1), S. Marcescens (1)
Platelets Pheresis microorganisms: S. aureus (4), S. epidermidis (1), M. morganii (1),, S. viridans (1), S. warneri (1), K. pneumoniae (1)
Figure 6: Bacterial Infection by Apheresis Platelets, FY2001 through FY2012
FY01:7; FY02:8; FY03:6; FY04:3; FY05:6; FY06:2; FY07:2; FY08:2; FY09:4; FY10:0; FY11:2; FY12:1
As noted above, 27 (36%) of the 74 reported fatalities in FY2012 were cases in which the transfusion could not be ruled out as the cause of the fatality. In these reported fatalities, the reporting facilities were unable to identify a specific complication of transfusion as the cause of death. Often, these patients had multiple co‑morbidities, and after review of the investigation documentation, our medical reviewers could neither confirm nor rule out the transfusion as the cause of the fatality (Table 4). Therefore, we did not include these 27 reported fatalities in the analysis in Sections II.A through II.D (transfusion-related fatalities).
After reviewing the initial fatality reports and the investigation documentation, we categorized 9 (12%) of the 74 reported fatalities as “Not Transfusion Related.” Our medical reviewers concluded that, while there was a temporal relationship between transfusion and subsequent death of the recipient, there was no evidence to support a causal relationship (Table 4). Thus, we did not include these reported fatalities in the analysis in Sections II.A through II.D (transfusion-related fatalities).
Table 4: Fatalities Not Related to Transfusion or Transfusion Not Ruled Out, FY2008 through FY2012 FY08 FY09 FY10 FY11 FY12 Transfusion Not Ruled Out 8 22 24 28 27 Not Transfusion Related 18 8 7 11 9 Total 26 30 31 39 36
In FY2012, there were 12 reports of fatalities following Source Plasma donation, and two reports of fatalities following Whole Blood donation. In 9 of the 12 Source Plasma donor deaths, and both Whole Blood donor deaths, although the donations could not be definitively ruled out as being implicated in the donors’ deaths, our medical reviewers found no evidence to support a causal relationship between the donations and subsequent death of the donors.
In 3 of the 12 reports of fatalities following Source Plasma donation in FY2012, the donations were definitively ruled out as being implicated in the death of the donors. In each of these cases, there was clear evidence showing the cause of death was unrelated to the donation.
Over the five-year reporting period there were four Source Plasma donations (three FY2012 reports and one FY2011 report), and one Whole Blood donation (FY2011) in which the donations were definitively ruled out as the cause of death. For the remaining cases, our medical reviewers concluded that, while there was a temporal link between the donations and the fatalities, there was no evidence to support a causal relationship between the donations and subsequent death of the donors (Table 5 and Figure7).28
Over the last three fiscal years, there has been an upward trend in the number of reported fatalities following Source Plasma donation. The FDA will continue to monitor and assess this trend, and has encouraged Industry to do the same.
Table 5: Post-Donation “Not Ruled Out” Fatality Reports by Donated Product, FY2008 through FY201228 Donated Product FY08 FY09 FY10 FY11 FY12 Source Plasma 7 3 2 6 9 Whole Blood 2 3 3 1 2 Apheresis Platelets 0 0 0 0 0 Apheresis Red Blood Cells 1 0 0 1 0 Total 10 6 5 8 11
Figure 7: Post-Donation “Not Ruled Out” Fatality Reports, FY2008 through FY201228
FY2008:Source Plasma:7;Whole Blood:2;Apheresis Platelets:0;Apheresis Red Blood Cells:1
FY2009:Source Plasma:3;Whole Blood:3;Apheresis Platelets:0;Apheresis Red Blood Cells:0
FY2010:Source Plasma:2;Whole Blood:3;Apheresis Platelets:0;Apheresis Red Blood Cells:0
FY2011:Source Plasma:6;Whole Blood:1;Apheresis Platelets:0;Apheresis Red Blood Cells:1
FY2012:Source Plasma:9;Whole Blood:2;Apheresis Platelets:0;Apheresis Red Blood Cells:0
1 Report of the US Department of Health and Human Services. The 2009 national blood collection and utilization survey report. Washington, DC: US Department of Health and Human Services, Office of the Assistant Secretary of Health, 2011.
3 The FY2005 - FY2007 data are not discussed in this report, but are available at: Annual Summary for Fiscal Years 2005 and 2006
14Wiersum-Osselton JC, Middleburg RA, Beckers EAM, et al. Male-only fresh frozen plasma for transfusion-related acute lung injury prevention: before-and-after comparative cohort study. Transfusion 2011;51:1278-1283.
20Eder A, Herron Jr R, Strupp A, et al. Effective reduction of transfusion-related lung injury risk with male-predominant plasma strategy in the American Red Cross (2006-2008). Transfusion 2010;50:1732-1742.
23Johnson ST, Van Tassell ER, et al. Babesia microti real-time polymerase chain reaction testing of Connecticut blood donors: potential implications for screening algorithms. Transfusion. doi: 10.1111/trf.12125.
27Eder AF, Kennedy JM, Dy BA, et al. American Red Cross Regional Blood Centers: Limiting and detecting bacterial contamination of apheresis platelets: inlet-line diversion and increased culture volume improve safety. Transfusion 2009;49:1554-1563.
28In previous fiscal years, discussion of the post-donation fatality reports has included all of the reported donor fatalities; in the current report, the reported donor fatalities in which the donation has been ruled out as the cause of death are not included in the discussion or representative data charts.