A comparison of transfusion-related adverse reactions among apheresis platelets, whole blood-derived platelets, and platelets subjected to pathogen reduction technology as reported to the National Healthcare Safety Network Hemovigilance Module.

Abstract

Despite advances in transfusion safety, concerns with safety of platelet transfusions remain including platelet-related sepsis and higher reaction rates observed among patients receiving apheresis platelets (APLTs). National Healthcare Safety Network (NHSN) Hemovigilance Module (HM) data were analyzed to quantify the burden and severity of adverse reactions occurring from APLTs and whole blood-derived platelets (WBD-PLTs). Facilities participating in NHSN HM during 2010–2018 were included. Adverse reaction rates (number per 100,000 components transfused) were calculated for APLTs and WBD-PLTs stratified by severity, use of platelet additive solution (PAS), and pathogen reduction technology (PRT). Chi-square tests were used to compare rates. During the study interval, 2,000,589 platelets were transfused: 1,435,154 APLTs; 525,902 WBD-PLTs; and among APLTs, 39,533 PRT-APLTs. APLT adverse reaction rates were higher (478 vs. 70/ 100,000, p<0.01) and more often serious (34 vs. 6/100,000; p<0.01) compared with WBD-PLTs. Adverse reactions were higher among PRT-APLTs (572/100,000) and were less often serious (18/100,000) compared with non-PRT-APLTs (35/100,000) although this association was not statistically significant. Among components implicated in adverse reactions, 92% of APLTs were suspended in plasma. Compared with PRT-APLTs stored in PAS, rates were higher among units stored in plasma (760 vs. 525/100,000). Most serious reactions (75%) were allergic. No transfusion-transmitted infections were reported among PRT-APLTs. APLTs were associated with a 6-fold and 2-fold higher serious adverse reaction risks compared with WBD-PLTs and PRT-APLTs, respectively. These findings demonstrate the importance of monitoring transfusion-related adverse reactions to track the safety of platelet transfusions and quantify the impact of mitigation strategies through national hemovigilance systems.

Introduction:

In the United States, nearly 2 million platelet transfusions are performed annually¹, with approximately 1 in 237 platelets transfused associated with an adverse reaction.² Although transfusion of blood components, overall, in the United States has declined since 2011, apheresis platelet (APLT) transfusions have increased by 2.3% since 2015, compared with a more than 50% decrease in whole blood-derived PLT (WBD-PLT) transfusions.¹ Manufacturing of WBD-PLTs involves pooling of donations from four or more donors, while APLTs are produced from a single donor.^{3, 4} While similar in clinical effectiveness, APLTs reduce the number of donor exposures to a recipient and therefore have been preferred due to perceived reduction in the risk of viral bloodborne pathogen transmission.^{3, 4} However, some studies have observed higher rates of infectious and non-infectious adverse reactions among APLT components compared with WBD-PLTs,^3-7 though one limited study found no significant difference between adverse reaction rates among the two collections methods.⁸

The mechanisms underlying differences in APLTs and WBD-PLTs are unclear but may include immunologic factors and production methods. Studies have suggested that this difference may be a result of higher plasma volumes contributed from a single donor in APLTs compared with WBD-PLTs.^{9, 10} High plasma volume products are implicated in some serious adverse reactions including acute hemolytic transfusion reactions and transfusion-related acute lung injury due to immune-mediated responses in the recipient related to antibodies present in the donated plasma.⁹

Historically, human immunodeficiency virus (HIV), hepatitis B virus (HBV), and hepatitis C virus (HCV) infections were of great concern as transfusion-transmissible infections. However, with the adoption of nucleic acid testing (NAT) of donors and rigorous donor selection, the risk of HIV, HBV, or HCV transmission through transfusion has dramatically decreased, with no reported transmissions through transfusion in the United States since 2014.^11-13 However, sepsis due to bacterial contamination of platelets continues to be a significant threat to recipient safety.¹⁴

Technological advances have resulted in enhanced transfusion recipient safety by mitigating the risk of some adverse reactions. Leukoreduction of platelets, typically at the time of product collection/processing, can reduce the occurrence of adverse reactions such as febrile non-hemolytic transfusion reactions.^{3, 4} Other manufacturing processes such as storage of collected platelets in a platelet additive solution have been found to decrease risk of adverse reactions associated with high volumes of plasma including acute hemolytic transfusion reactions.^{15, 16}

In 2014, the U.S. Food and Drug Administration (FDA) approved a pathogen reduction technology (PRT) device for APLTs as a safety measure to mitigate the occurrence of transfusion-related adverse reactions including sepsis due to bacterial contamination, transfusion-transmitted infections and transfusion-associated graft-vs-host disease.^{14, 17} In the United States, PRT-APLTs can be stored in plasma or in an additive solution, which replaces approximately 65% of plasma volume with an isotonic solution and may further reduce the risk of adverse reactions compared with components suspended in plasma.^{16, 18}

A previous publication using data reported to the National Healthcare Safety Network Hemovigilance Module during 2010–2012 described higher rates of transfusion-related adverse reactions among APLTs compared with WBD-PLTs.² Here we report results from analyses of a more expansive dataset obtained from the NHSN HM from 2010-2018 to determine if such trends continue and to describe in more detail the occurrence and types of transfusion-related adverse reactions associated with PLT transfusions. In particular, results from analyses comparing transfusion-related adverse reaction rates among APLT and WBD-PLT components, transfusion-related adverse reaction rates among PRT-APLT and non-PRT-APLT components, and estimates of transfusion-related adverse reactions associated with PLT storage in platelet additive solution and plasma are described.

Methods

Ethical Consideration

Data for this study were collected for surveillance and program evaluation purposes and determined to not require institutional review board review by Centers for Disease Control and Prevention (CDC) Office of the Associate Director for Science. Individual and institutional identifiers reported to NHSN are confidential and not disclosed by CDC without consent of the participating facility.

Data Collection

Facilities with adverse reactions reported to NHSN HM during 2010–2018 were included in these analyses. Transfusion-related adverse reactions included: acute hemolytic, allergic, circulatory overload, febrile non-hemolytic, hypotensive, transfusion-associated dyspnea, transfusion-related acute lung injury, and transfusion-transmitted infection.

For each reaction, a case definition (definite, probable or possible), imputability (definite, probable, possible, doubtful, ruled out, or not determined) and severity (non-severe, severe, life-threatening, fatal, or not determined) were assigned based on the module protocol.¹⁹ Reactions that met case definition criteria and imputability of definite, probable, or possible as described in the protocol were included.¹⁹ Adverse reactions that did not meet specified case criteria or were designated as “other” or “unknown” reactions, and those with imputability criteria of doubtful, ruled out, or not determined were excluded.

Facilities are required to report ISBT-128 component codes for blood products implicated in the adverse reaction. ISBT-128 codes were used to determine reactions associated with APLT components suspended in PAS and plasma. Components suspended in PAS and plasma were available for PRT-APLT components contributing to rate calculations.

Data were included from facilities reporting at least one month of denominator data from January 1, 2010–December 31, 2018. Adverse reactions meeting case definition and imputability criteria and associated with a PLT component were included.

Definitions

Facility characteristics included community setting (urban, suburban, rural),²⁰ total beds served by the transfusion service (≤249, 250-499, 500-749, ≥750), number of transfusion service staff members based on full-time equivalents (<5, 5-9, 10-19, ≥20), employment of a full-time quality assurance staff member, and the transfusion service provider (facility provides own transfusion services, separate facility, or blood collection center or centralized transfusion service).

Reactions meeting case definition and imputability criteria were used as numerators. Total transfused APLT and WBD-PLT components were used as denominators. Rates were calculated by collection method per 100,000 components transfused for the following: healthcare facility characteristics; total and individual reaction types; and serious reactions (fatal, life threatening or severe). Adverse reaction rates were also calculated for PRT-APLT and non-PRT-APLT components and, among these, storage in additive solution or plasma. Reactions attributed to transfused APLTs were stratified by the use of a platelet additive solution or suspension in plasma. Data as to whether a product was suspended in a platelet additive solution or in plasma were only available for products associated with reactions and for PRT products transfused, and not for all platelets.

Statistical Analysis

Rate differences were determined using χ2 tests or Fisher tests when one of the cell sizes were less than five. Rate differences were calculated between the following: overall APLTs and WBD-PLTs, PRT-APLTs and non-PRT-APLTs, and PRT-APLTs in PAS and PRT-APLTs in plasma. For these comparisons, the significance level was set at p<0.05. All analyses were performed using the SAS version 9.4 statistical software (SAS Institute, Inc., Cary, NC).

Results

During 2010–2018, 386 healthcare facilities were enrolled in the NHSN HM, which represents approximately 10% of all acute care facilities in the United States which perform inpatient transfusions.^{1, 21} Of these, 280 completed the annual facility survey. Among these 280 facilities, 215 (77%) facilities submitted at least one month of data on transfused components and were included in the analyses. From 215 facilities, 29,624 total adverse reactions were reported. Of these adverse reactions, 23,599 met case definition and imputability criteria, of which 7,421 were associated with 2,000,589 transfused PLT components (Figure 1). The number of facilities reporting to the NHSN HM has increased considerably throughout the years from 26 in 2010 to a peak of 151 in 2014 but has since declined to 132 facilities in 2018.

Figure 1.

Facility participation and data inclusion for analyses of transfusion-related adverse reactions among platelet components reported to the NHSN Hemovigilance Module, 2010 to 2018.

Table 1 describes characteristics of the 215 healthcare facilities included in the study during 2010–2018. More than half of facilities (111, 52%) were in urban settings and a third (72, 33%) were suburban. The largest proportion of facilities were those with ≤249 beds (43%); approximately a third (35%) had 250–499 beds. Adverse reactions among APLTs were higher across all facility types compared with WBD-PLTs, with rates highest in rural settings (665/100,000), facilities with 250–499 beds (558/100,000) and facilities in which transfusion services were provided by a blood collection center (503/100,000).

TABLE 1.

Facility size, number of transfusion service staff, employment of a quality assurance staff member to investigate transfusion-related adverse reactions, transfusion service provider, and community setting for health care facilities reporting to the NHSN Hemovigilance Module, 2010-2018.

Facility characteristics	Number of facilities (% of total)
Total facilities	215 (100.0%)
Number of inpatient beds
≤249	93 (43.3%)
250-499	75 (34.9%)
500-749	25 (11.6%)
≥750	22 (10.2%)
Number of transfusion service staff
Less than 5	53 (24.7%)
5 to 9	65 (30.2%)
10 to 19	56 (26.0%)
20 or more	37 (17.2%)
Facility employs a full-time quality assurance staff member?
Yes	76 (35.3%)
No	139 (64.7%)
Facility's transfusion service provided by…
Facility	125 (58.1%)
Separate facility	15 (7.0%)
Blood collection center or centralized transfusion service	67 (31.2%)
Urban/rural
Urban	111 (51.6%)
Suburban	72 (33.5%)
Rural	31 (14.4%)

During the study period, 7,055 reactions among APLTs and 366 reactions among WBD-PLTs met case definition and imputability criteria (Table 2a). The overall adverse reaction rate was higher among APLTs compared with WBD-PLTs (478/100,000 vs. 70/100,000; p<0.01). Among WBD-PLTs, febrile non-hemolytic reactions occurred at the highest rate (38/100,000). Among APLTs, allergic reactions occurred at the highest rate (325/100,000). Difference in the rate of reactions for WBD-PLTs and APLTs were significant for: allergic, febrile non-hemolytic, transfusion-associated dyspnea, hypotensive, acute hemolytic, and transfusion-related acute lung injury. Rates of transfusion-transmitted infections were not significantly different among APLT and WBD-PLT components (Table 2a).

TABLE 2a.

Total numbers of adverse reactions among transfused platelet components, adverse reaction rates per 100,000 units transfused stratified by severity and collection methods as reported to the NHSN Hemovigilance Module, 2010-2018.

Adverse Reaction*	PLT reactions, N (rate per 100,000)
	WBD PLT (denominator: 525,902 units)	95% CI for WBD PLT rates	APLT (denominator: 1,474,687 units)	95% CI for APLT rates	p-value†
All adverse reactions	366 (69.59)	60-80	7,055 (478.41)	470-490	<.01
All serious adverse reactions	32 (6.08)	4-9	504 (34.18)	30-40	<.01
Fatal reactions	1 (0.19)	0-1	6 (0.41)	0-1	0.47
Allergic	143 (27.19)	20-30	4,793 (325.02)	320-330	<.01
Serious reactions	16 (3.04)	0-5	386 (26.18)	20-30	<.01
Fatal reactions	0 (-)	0-1	1 (0.07)	0-1	1.00
Febrile nonhemolytic	198 (37.65)	30-40	2,006 (136.03)	130-140	<.01
Serious reactions	8 (1.52)	0-3	36 (2.44)	0-3	0.22
Transfusion-associated circulatory overload‡	7 (1.33)	0-3	8 (0.54)	0-1	0.07
Serious reactions	2 (0.38)	0-2	1 (0.07)	0-1	0.17
Transfusion-associated dyspnea	7 (1.33)	0-3	85 (5.76)	0-1	<.01
Serious reactions	1 (0.19)	0-1	17 (1.15)	0-2	0.06
Hypotensive	3 (0.57)	0-2	78 (5.29)	0-1	<.01
Serious reactions	1 (0.19)	0-1	25 (1.70)	0-3	0.01
Acute hemolytic‡	1 (0.19)	0-1	26 (1.76)	0-3	<.01
Serious reactions	0 (-)	0-1	7 (0.47)	0-1	0.20
Transfusion-related acute lung injury‡	1 (0.19)	0-1	22 (1.49)	0-2	0.02
Serious reactions	0 (-)	0-1	15 (1.02)	0-2	0.02
Fatal reactions	0 (-)	0-1	3 (0.20)	0-1	0.57
Transfusion-transmitted infection§	4 (0.76)	0-2	21 (1.42)	0-2	0.36
Serious reactions	4 (0.76)	0-2	16 (1.08)	0-2	0.62
Fatal reactions	1 (0.19)	0-1	2 (0.13)	0-1	1.00

PLT= platelet

WBD= whole blood-derived

APLT= apheresis platelet

CI: confidence interval

N= total number of reactions reported

^*Serious reactions include fatal, life threatening and severe reactions

^†p-values were calculated to assess the statistical significance and test rate differences between WBD and apheresis PLTs. The significance level was set at p<0.05 and significant differences are bolded.

^‡All platelet components associated with these reactions were suspended in plasma. These reactions include acute hemolytic transfusion reaction, transfusion-associated circulatory overload and transfusion-related acute lung injury.

^§All reported transfusion transmitted infections were associated with bacterially contaminated platelets.

Most (93%) adverse reactions were not serious (Table 2a). Of 536 (7%) serious reactions, 504 (94%) occurred among APLTs. Serious reaction rates were more than five-fold higher among APLTs (34/100,000 vs 6/100,000 for WBD-PLTs; p<0.01). Among both component types, serious reactions were most commonly allergic (26 and 3/100,000). The majority of transfusion-related acute lung injury (65%; 15/23) and transfusion-transmitted infections (80%; 20/25) were designated as serious (Table 2a).

Transfusion-transmitted infections comprised <1% (25/7,421) of all reactions and 4% (20/536) of serious reactions, and all were attributable to sepsis due to bacterial contamination. The rate of transfusion-transmitted infections was almost two times higher among APLTs compared with WBD-PLTs, though this difference did not meet statistical significance (1.42 vs 0.76/100,000; p=0.36). Transfusion-related acute lung injury was uncommon (<1% (23/7,421) of all reactions) but occurred more often among APLTs than among WBD-PLTs (1.49 vs 0.19/100,000; p=0.02) (Table 2a). While acute hemolytic reactions were also uncommon (<1% (27/7,421) of reactions reported), these occurred more often among APLTs (1.76 vs 0.19/100,000; p<0.01). All serious acute hemolytic transfusion reactions identified in this study were associated with APLT transfusions (Table 2a).

Use of platelet additive solution and PRT among APLT components is described in Table 2b. Of the 7,055 reactions associated with APLTs, 561 (8%) were suspended in a platelet additive solution. Among these components, there were no reports of acute hemolytic reactions or transfusion-related acute lung injury. Of the 1,474,687 APLT components implicated, 39,533 (3%) components were PRT-APLTs. Transfusion-transmitted infections were not reported among PRT-APLTs. The adverse reaction rate was higher among PRT-APLTs compared with non-PRT-APLTs (572 vs 476/100,000; p<0.01). Serious reactions were lower among PRT-APLTs, although this difference was not statistically significant (18 vs 35/100,000; p=0.07). Among PRT-APLTs, 45% (17,729/39,533) were suspended in a platelet additive solution. Of the 226 reactions associated with PRT-APLTs, additive solution was used in platelet products implicated among 93 (41%) reactions (Table 2c). Overall reaction rates among components suspended in platelet additive solution were lower than compared with those suspended in plasma (525 vs. 760/100,000) (Table 2c).

TABLE 2b.

Total numbers of adverse reactions among transfused apheresis platelet components, adverse reaction rates per 100,000 units transfused stratified by severity and use of pathogen reduction technology as reported to the NHSN Hemovigilance Module, 2010-2018.

Adverse Reaction*	APLT reactions, N (rate per 100,000)
	PR-APLT† (denominator: 39,533 units)	95% CI for PR-APLT rates	Non-PR-APLT† (denominator: 1,435,154 units)	95% CI for Non-PR-APLT rates	p-value‡
All adverse reactions	226 (571.67)	500-650	6,829 (475.84)	460-490	<.01
All serious adverse reactions	7 (17.71)	10-40	497 (34.63)	32-38	0.07
Fatal reactions	0 (-)	0-10	6 (0.42)	0-1	1.00
Allergic	99 (250.42)	200-300	4,694 (327.07)	320-340	<.01
Serious reactions	5 (12.65)	0-30	381 (26.55)	24-29	0.11
Fatal reactions	0 (-)	0-10	1 (0.07)	0-1	1.00
Febrile nonhemolytic	123 (311.13)	260-370	1,883 (131.21)	130-140	<.01
Serious reactions	1 (2.53)	0-10	35 (2.44)	0-3	0.62
Transfusion-associated circulatory overload§	0 (-)	0-10	8 (0.56)	0-1	1.00
Serious reactions	0 (-)	0-10	1 (0.07)	0-1	1.00
Transfusion-associated dyspnea	3 (7.59)	0-20	82 (5.71)	0-10	0.50
Serious reactions	1 (2.53)	0-10	16 (1.11)	0-2	0.37
Hypotensive	1 (2.53)	0-10	77 (5.37)	0-10	0.73
Serious reactions	0 (-)	0-10	25 (1.74)	0-3	1.00
Acute hemolytic§	0 (-)	0-10	26 (1.81)	0-3	1.00
Serious reactions	0 (-)	0-10	7 (0.49)	0-1	1.00
Transfusion-related acute lung injury§	0 (-)	0-10	22 (1.53)	0-2	1.00
Serious reactions	0 (-)	0-10	15 (1.05)	0-2	1.00
Fatal reactions	0 (-)	0-10	3 (0.21)	0-1	1.00
Transfusion-transmitted infection∥	0 (-)	0-10	21 (1.46)	0-2	1.00
Serious reactions	0 (-)	0-10	16 (1.11)	0-2	1.00
Fatal reactions	0 (-)	0-10	2 (0.14)	0-1	1.00

APLT= apheresis platelet

PR-APLT= pathogen reduced apheresis platelet

Non-PRT-APLT= non-pathogen reduced apheresis platelet

CI= confidence interval

N= total number of reactions reported

^*Serious reactions include fatal, life threatening and severe reactions

^†PRT treated apheresis PLT components and associated reactions are a subset of all apheresis PLT components transfused.

^‡p-values were calculated to assess the statistical significance and test rate differences between PR-APLT and non-PRT APLT. The significance level was set at p<0.05 and significant differences are bolded.

^§All platelet components associated with these reactions were suspended in plasma. These reactions include acute hemolytic transfusion reaction, transfusion-associated circulatory overload and transfusion-related acute lung injury.

^∥All reported transfusion transmitted infections were associated with bacterially contaminated platelets.

TABLE 2c.

Total numbers of adverse reactions among transfused pathogen reduced apheresis platelet components, adverse reaction rates per 100,000 units transfused stratified by severity and use of platelet additive solution as reported to the NHSN Hemovigilance Module, 2010-2018.

Adverse Reaction*	PR-APLT reactions, N (rate per 100,000) ∥
	PR-APLT in PAS† (denominator: 17,729 units)	95% CI for PR-APLT in PAS rates	PR-APLT in plasma (denominator: 17,500 units)	95% CI for PR-APLT in plasma rates	p-value‡
All adverse reactions	93 (524.56)	420-640	133 (760.00)	640-900	<.01
All serious adverse reactions	5 (28.20)	10-70	2 (11.43)	0-40	0.26
Fatal reactions	0 (-)	0-20	0 (-)	0-20	--
Allergic	29 (163.57)	110-230	70 (400.00)	310-500	<.01
Serious reactions	3 (16.92)	0-30	2 (11.43)	0-40	0.67
Fatal reactions	0 (-)	0-20	0 (-)	0-20	--
Febrile nonhemolytic	60 (338.43)	260-440	63 (360.00)	270-460	0.73
Serious reactions	1 (5.64)	0-30	0 (-)	0-20	0.32
Transfusion-associated circulatory overload∥	0 (-)	0-20	0 (-)	0-20	--
Serious reactions	0 (-)	0-20	0 (-)	0-20	--
Transfusion-associated dyspnea	3 (16.92)	0-50	0 (-)	0-20	0.09
Serious reactions	1 (5.64)	0-30	0 (-)	0-20	1.00
Hypotensive	1 (5.64)	0-30	0 (-)	0-20	1.00
Serious reactions	0 (-)	0-20	0 (-)	0-20	--
Acute hemolytic∥	0 (-)	0-20	0 (-)	0-20	--
Serious reactions	0 (-)	0-20	0 (-)	0-20	--
Transfusion-related acute lung injury∥	0 (-)	0-20	0 (-)	0-20	--
Serious reactions	0 (-)	0-20	0 (-)	0-20	--
Fatal reactions	0 (-)	0-20	0 (-)	0-20	--
Transfusion-transmitted infection¶	0 (-)	0-20	0 (-)	0-20	--
Serious reactions	0 (-)	0-20	0 (-)	0-20	--
Fatal reactions	0 (-)	0-20	0 (-)	0-20	--

PR-APLT= pathogen reduced apheresis platelet

PAS= platelet additive solution

CI= confidence interval

N= total number of reactions reported

^*Serious reactions include fatal, life threatening and severe reactions

^†PAS: platelet additive solution; components suspended in PAS and plasma were only available for PR-APLT components in NHSN Hemovigilance Module.

^‡p-values were calculated to assess the statistical significance and test rate differences between PR-APLT in PAS and PR-APLT in plasma. The significance level was set at p<0.05 and significant differences are bolded.

^§Reaction rates were calculated per 100,000 total components transfused for each component type; information on use of PAS was not available for total WBD and apheresis PLT components transfused but was available for total PRT apheresis PLTs transfused

^∥All platelet components associated with these reactions were suspended in plasma. These reactions include acute hemolytic transfusion reaction, transfusion-associated circulatory overload and transfusion-related acute lung injury.

^¶All reported transfusion transmitted infections were associated with bacterially contaminated platelets.

Data on age of platelet in days were available for 1,930 reactions associated with APLTs and 204 reactions associated with WBD-PLTs. Of the 1,930 reactions among APLTs, 4% (6/1,930) were 0-2 days old, 15% (285/1,930) were 3 days old, 33% (641/1,930) were 4 days old, and 48% (936/1,930) were 5 days old. Of the 204 reactions among WBD-PLTs, 1% (2/204) were 0-2 days old, 8% (17/204) were 3 days old, 22% (44/204) were 4 days old, and 69% (44/204) were 5 days old.

Discussion

This study analyzed data reported to the NHSN HM during 2010–2018 on 7,421 transfusion-related adverse reactions associated with >2 million transfused PLT components including nearly 40,000 PRT-APLTs. Consistent with previous studies, these analyses found transfusion-related adverse reaction rates were higher and more often serious among APLTs compared with WBD-PLT products.^{5, 6, 22} Adverse reaction rates among PRT-APLTs were higher but less often serious compared with non-PRT-APLTs. Moreover, transfusion-transmitted infections were not reported among PRT-APLTs. This study also observed a small proportion of reactions were associated with APLT components suspended in platelet additive solution. Consistent with previous studies, platelets collected in an additive solution, particularly when subjected to PRT, had fewer reported reactions.¹⁶ Since the first NHSN HM report examining transfusion related adverse reactions during 2010-2012, several safety measures have been implemented in the United States including the FDA-approved PRT device for apheresis platelets. This study examined transfusion-related adverse reactions occurring from platelet products in detail and expanded on the previous study to include the use of PRT among APLTs and PAS among PRT-APLTs. Compared with the previous NHSN HM study, this study observed a higher rate of transfusion transmitted infections among APLTs, although this was not statistically significant. As transfusion-related adverse reactions, including serious reactions, continue to occur at higher rates among APLT components, additional research is necessary to elucidate the reasons for these differences when compared with WBD-PLTs.

It has been suggested that APLTs may be implicated more often in serious reactions due to higher plasma volumes which characterize these products. Additional studies examining this particular premise are needed to help clarify the roles, if any, of the magnitude of the volume or the qualitative composition of these products are contributory to the observed trends. In this regard, one method to reduce risk of reactions occurring from transfused APLTs includes the use of platelet additive solutions to reduce plasma volume.^{16, 18} Utilization of platelet additive solution has been described to decrease reactions by >30% in comparison with platelet components stored in plasma.^{16, 18} Overall adverse reactions among components suspended in platelet additive solution were lower compared to those suspended in plasma in this study, suggesting reduced risk of adverse reactions associated with these components.

These data further demonstrate an evolution of transfusion-transmitted infection concerns from viral bloodborne pathogens to bacterial infections. In the present study, septic transfusion reactions occurred among both WBD-PLTs and APLTs, though the rate was higher among APLTs. Differences in reaction rates may also be attributable to variation in apheresis collection procedures including instrument type. Higher rates of septic transfusion reactions were previously observed among APLTs collected through plateletpheresis from the Amicus device.²³

The findings of the present study support the adoption of additional measures to reduce risk of bacterial contamination. In 2019, FDA guidance outlined platelet bacterial risk mitigation strategies.²⁴ These recommendations include PRT or the use of two step strategies for APLTs in order to enhance bacterial detection. Reports of sepsis due to bacterial contamination were not associated with PRT-APLTs in the present study, suggesting this method is effective in mitigating risk of bacterial contamination, though rare cases of bacterial contamination have been described with PRT-APLTs.²⁵ However, since the time period of the current analysis did not include implementation of the updated bacterial mitigation strategies, CDC will continue to monitor the impact of guidance on septic reaction rates among platelet products.

These findings are subject to several limitations. First, the 215 participating facilities in this study were not a statistically representative sample of all U.S. hospitals performing transfusions. Of the 215 facilities, 73 (34%) are located in Massachusetts due to a statewide mandate for reporting of transfusion-related adverse events. While these findings may not be generalizable to the entire country, they are comparable to those of other hemovigilance systems and provide useful insight into additional measures which may enhance blood safety.²⁶ Second, data reported in the NHSN HM are self-reported by facilities, which may result in underreporting or misclassification of adverse reactions. To improve accuracy, CDC has implemented automated designations into the NHSN HM for case definition and imputability criteria for reported reactions based on laboratory findings and signs and symptoms relative to transfusion. Third, components suspended in platelet additive solution or plasma were only available for PRT-APLTs in NHSN HM and not available for all transfused platelet components, limiting rate calculations. Additionally, data in NHSN were not available to compare reaction rates among different patient populations, apheresis collection platforms or bacterial detection methods that may have contributed to observed differences.

In conclusion, we have reported results from analyses of a more expansive dataset obtained from the NHSN HM from 2010-2018 to determine if trends regarding PLT transfusions and reactions associated with them have continued as described in previous studies. Our findings demonstrate the importance of monitoring transfusion-related adverse reactions to track the safety of platelet transfusions and quantify the impact of mitigation strategies through national hemovigilance systems. Results from our study, as well as those of others, highlight the need to support continued and expanded participation in the NHSN Hemovigilance Module by U.S. healthcare facilities and monitoring by public health organizations. Such monitoring is key in the assessment of current and potential future threats impacting blood safety including but not limited to quantifying the risk of sepsis due to bacterial contamination on a national level and in the on-going assessment of the impact of various mitigation strategies in ameliorating this threat.

Highlights:

• This analysis included >2 million platelet transfusions, with an APLT: WBD-PLT ratio of 2.7: 1.

• APLT adverse reaction rates were higher and more often serious compared with WBD-PLTs.

• Adverse reactions were higher among PRT-APLTs but were less often serious compared with non-PRT-APLTs, although this association was not significant.

• No transfusion-transmitted infections were reported among PRT-APLTs.

• Fatalities were rare among transfused platelet components. There were 7 fatalities reported and 7% of all adverse reactions were serious (severe, life-threatening, or fatal).