Abstract

Cardiorespiratory complications after blood transfusion are the leading cause of transfusion-related morbidity and mortality worldwide. Transfusion-related acute lung injury (TRALI) and transfusion-associated circulatory overload (TACO) are the 2 most frequently reported cardiorespiratory complications, both of which have clear pathophysiology-based treatment algorithms. In the past decades, translational research has increased understanding of mechanisms in place, including patient and transfusion risk factors. This has led to updated international definitions, biomarker-based diagnostics, interventions, and risk mitigation measures. Preventive measures have led to a significant reduction in TRALI, and TACO prevention is increasingly highlighted within hemovigilance. In this article, clinical case scenarios illustrate the challenges of diagnosing, treating, and finally classifying cardiorespiratory complications of transfusion. A background on current definitions, diagnostics, and pathophysiological mechanisms will be given, as well as how to deal with cases in which TRALI and TACO are both present. Hemovigilance systems worldwide are essential to provide insight into the incidence of transfusion complications. Furthermore, these systems provide a basis to discover new patient and transfusion risk factors and to better balance the down- and upside of a transfusion for a patient. Finally, we discuss the future challenges and research priorities in the field of cardiorespiratory transfusion-related complications.

1.
Transfusion and Transplantation Reactions in Patients (TRIP)
.
TRIP report 2022, extended version: Hemovigilance
. Accessed 23 October 2024. https://www.tripnet.nl/wp-content/uploads/2024/07/TRIPJaarrapportHemo2022EN-website-met-links.pdf.
2.
Fatalities Reported to FDA Following Blood Collection and Transfusion. Annual Summary for Fiscal Year 2021. US Food and Drug Administration 2023
. Accessed 24 April 2024. https://www.fda.gov/media/172382/download?attachment.
3.
Narayan
S
, et al
.
The 2023 Annual SHOT Report, Manchester: Serious Hazards of Transfusion (SHOT) Steering Group
.
2024
https://doi.org/10.57911/605r-em59.
4.
Bosboom
JJ
,
Klanderman
RB
,
Zijp
M
, et al
.
Incidence, risk factors, and outcome of transfusion-associated circulatory overload in a mixed intensive care unit population: a nested case-control study
.
Transfusion
.
2018
;
58
(
2
):
498
-
506
.
5.
Bosboom
JJ
,
Klanderman
RB
,
Migdady
Y
, et al
.
Transfusion-associated circulatory overload: a clinical perspective
.
Transfus Med Rev
.
2019
;
33
(
2
):
69
-
77
.
6.
Vlaar
AP
,
Binnekade
JM
,
Prins
D
, et al
.
Risk factors and outcome of transfusion-related acute lung injury in the critically ill: a nested case-control study
.
Crit Care Med
.
2010
;
38
(
3
):
771
-
778
.
7.
Vlaar
AP
,
Juffermans
NP
.
Transfusion-related acute lung injury: a clinical review
.
Lancet
.
2013
;
382
(
9896
):
984
-
994
.
8.
Delaney
M
,
Wendel
S
,
Bercovitz
RS
, et al
.
Transfusion reactions: prevention, diagnosis, and treatment
.
Lancet
.
2016
;
388
(
10061
):
2825
-
2836
.
9.
Vlaar
APJ
,
Toy
P
,
Fung
M
, et al
.
A consensus redefinition of transfusion-related acute lung injury
.
Transfusion
.
2019
;
59
(
7
):
2465
-
2476
.
10.
Force
ADT
,
Ranieri
VM
,
Rubenfeld
GD
, et al
.
Acute respiratory distress syndrome: the Berlin definition
.
JAMA
.
2012
;
307
(
23
):
2526
-
2533
.
11.
Yuan
Y
,
Dennington
PM
,
Daly
J
,
Baidya
S
,
Tung
JP
.
The impact of revised definitions for transfusion-associated circulatory overload and transfusion-related acute lung injury on haemovigilance reporting
.
Vox Sang
.
2023
;
118
(
3
):
199
-
206
.
12.
Klanderman
RB
,
Bulle
EB
,
Heijnen
JWM
, et al
.
Reported transfusion-related acute lung injury associated with solvent/detergent plasma - a case series
.
Transfusion
.
2022
;
62
(
3
):
594
-
599
.
13.
Klanderman
RB
,
van Mourik
N
,
Eggermont
D
, et al
.
Incidence of transfusion-related acute lung injury temporally associated with solvent/detergent plasma use in the ICU: a retrospective before and after implementation study
.
Transfusion
.
2022
;
62
(
9
):
1752
-
1762
.
14.
Silliman
CC
.
The two-event model of transfusion-related acute lung injury
.
Crit Care Med
.
2006
;
34
(
5 Suppl
):
S124
-
S131
.
15.
Vlaar
AP
,
Hofstra
JJ
,
Levi
M
, et al
.
Supernatant of aged erythrocytes causes lung inflammation and coagulopathy in a "two-hit" in vivo syngeneic transfusion model
.
Anesthesiology
.
2010
;
113
(
1
):
92
-
103
.
16.
Vlaar
AP
,
Hofstra
JJ
,
Kulik
W
, et al
.
Supernatant of stored platelets causes lung inflammation and coagulopathy in a novel in vivo transfusion model
.
Blood
.
2010
;
116
(
8
):
1360
-
1368
.
17.
Peters
AL
,
Van Stein
D
,
Vlaar
AP
.
Antibody-mediated transfusion-related acute lung injury; from discovery to prevention
.
Br J Haematol
.
2015
;
170
(
5
):
597
-
614
.
18.
Peters
AL
,
van Hezel
ME
,
Juffermans
NP
,
Vlaar
AP
.
Pathogenesis of non-antibody mediated transfusion-related acute lung injury from bench to bedside
.
Blood Rev
.
2015
;
29
(
1
):
51
-
61
.
19.
Carcano
C
,
Okafor
N
,
Martinez
F
,
Ramirez
J
,
Kanne
J
,
Kirsch
J
.
Radiographic manifestations of transfusion-related acute lung injury
.
Clin Imag
.
2013
;
37
(
6
):
1020
-
1023
.
20.
Vlaar
AP
,
Porcelijn
L
,
van Rooijen-Schreurs
IH
,
Lardy
NM
,
Kersten
MJ
,
Juffermans
NP
.
The divergent clinical presentations of transfusion-related acute lung injury illustrated by two case reports
.
Med Sci Monit
.
2010
;
16
(
10
):
CS129
-
C134
.
21.
Bux
J
,
Sachs
UJ
.
The pathogenesis of transfusion-related acute lung injury (TRALI)
.
Br J Haematol
.
2007
;
136
(
6
):
788
-
799
.
22.
Peters
AL
,
Van De Weerdt
EK
,
Goudswaard
EJ
, et al
.
Reporting transfusion-related acute lung injury by clinical and preclinical disciplines
.
Blood Transfus
.
2018
;
16
(
3
):
227
-
234
.
23.
Vlaar
AP
,
Wortel
K
,
Binnekade
JM
, et al
.
The practice of reporting transfusion-related acute lung injury: a national survey among clinical and preclinical disciplines
.
Transfusion
.
2010
;
50
(
2
):
443
-
451
.
24.
Wiersum-Osselton
JC
,
Whitaker
B
,
Grey
S
, et al
.
Revised international surveillance case definition of transfusion-associated circulatory overload: a classification agreement validation study
.
Lancet Haematol
.
2019
;
6
(
7
):
e350
-
e358
.
25.
Bulle
EB
,
Klanderman
RB
,
Pendergrast
J
,
Cserti-Gazdewich
C
,
Callum
J
,
Vlaar
APJ
.
The recipe for TACO: a narrative review on the pathophysiology and potential mitigation strategies of transfusion-associated circulatory overload
.
Blood Rev
.
2022
;
52
:
100891
.
26.
Bulle
EB
,
Blanken
B
,
Klanderman
RB
,
van Manen
L
,
Juffermans
NP
,
Vlaar
APJ
.
Exploring NT-proBNP, syndecan-1, and cytokines as biomarkers for transfusion-associated circulatory overload in a critically ill patient population receiving a single-unit red blood cell transfusion
.
Transfusion
.
2023
;
63
(
11
):
2052
-
2060
.
27.
Parmar
N
,
Pendergrast
J
,
Lieberman
L
,
Lin
Y
,
Callum
J
,
Cserti-Gazdewich
C
.
The association of fever with transfusion-associated circulatory overload
.
Vox Sang
.
2017
;
112
(
1
):
70
-
78
.
28.
Klanderman
RB
,
Bosboom
JJ
,
Maas
AAW
, et al
.
Volume incompliance and transfusion are essential for transfusion-associated circulatory overload: a novel animal model
.
Transfusion
.
2019
;
59
(
12
):
3617
-
3627
.
29.
Klanderman
RB
,
Wijnberge
M
,
Bosboom
JJ
, et al
.
Differential effects of speed and volume on transfusion-associated circulatory overload: a randomized study in rats
.
Vox Sang
.
2022
;
117
(
3
):
371
-
378
.
30.
Bulle
EB
,
Klanderman
RB
,
de Wissel
MB
, et al
.
The effect of plasma transfusion in an experimental two-hit animal model of transfusion-associated circulatory overload with heart failure
.
Blood Transfus
.
2023
;
21
(
3
):
218
-
226
.
31.
Bulle
EB
,
Klanderman
RB
,
de Wissel
MB
, et al
.
Can volume-reduced plasma products prevent transfusion-associated circulatory overload in a two-hit animal model?
.
Vox Sang
.
2023
;
118
(
3
):
185
-
192
.
32.
Bosboom
JJ
,
Klanderman
RB
,
Peters
AL
, et al
.
The practice of diagnosing and reporting transfusion-associated circulatory overload: a national survey among physicians and haemovigilance officers
.
Transfus Med
.
2018
;
28
(
5
):
363
-
370
.
33.
Vlaar
APJ
,
Dionne
JC
,
de Bruin
S
, et al
.
Transfusion strategies in bleeding critically ill adults: a clinical practice guideline from the European Society of Intensive Care Medicine
.
Intensive Care Med
.
2021
;
47
(
12
):
1368
-
1392
.
34.
Vlaar
AP
,
Oczkowski
S
,
de Bruin
S
, et al
.
Transfusion strategies in non-bleeding critically ill adults: a clinical practice guideline from the European Society of Intensive Care Medicine
.
Intensive Care Med
.
2020
;
46
(
4
):
673
-
696
.
35.
Klanderman
RB
,
Attaye
I
,
Bosboom
JJ
,
Veelo
DP
,
Geerts
BF
,
Vlaar
APJ
.
Transfusion-associated circulatory overload: a survey among Dutch intensive care fellows
.
Transfus Clin Biol
.
2018
;
25
(
1
):
19
-
25
.
36.
Li
G
,
Rachmale
S
,
Kojicic
M
, et al
.
Incidence and transfusion risk factors for transfusion-associated circulatory overload among medical intensive care unit patients
.
Transfusion
.
2011
;
51
(
2
):
338
-
343
.
37.
Klanderman
RB
,
Bosboom
JJ
,
Migdady
Y
, et al
.
Transfusion-associated circulatory overload-a systematic review of diagnostic biomarkers
.
Transfusion
.
2019
;
59
(
2
):
795
-
805
.
38.
Marik
PE
,
Corwin
HL
.
Acute lung injury following blood transfusion: expanding the definition
.
Crit Care Med
.
2008
;
36
(
11
):
3080
-
3084
.
39.
National Heart Lung and Blood Institute Acute Respiratory Distress Syndrome ARDS Clinical Trials Network
,
Wiedemann
HP
,
Wheeler
AP
,
Bernard
GR
, et al
.
Comparison of two fluid-management strategies in acute lung injury
.
N Engl J Med
.
2006
;
354
(
24
):
2564
-
2575
.
40.
Bux
J
,
Sachs
UJ
.
Pulmonary transfusion reactions
.
Transfus Med Hemother
.
2008
;
35
(
5
):
337
-
345
.
41.
Roubinian
NH
,
Chowdhury
D
,
Hendrickson
JE
, et al
.
NT-proBNP levels in the identification and classification of pulmonary transfusion reactions
.
Transfusion
.
2020
;
60
(
11
):
2548
-
2556
.
42.
Drummond
R
.
Transfusion reactions and fatalities due to circulatory overloading
.
Br Med J
.
1943
;
2
(
4314
):
319
-
322
.
43.
Popovsky
MA
,
Moore
SB
.
Diagnostic and pathogenetic considerations in transfusion-related acute lung injury
.
Transfusion
.
1985
;
25
(
6
):
573
-
577
.
44.
van Wonderen
SF
,
Peters
AL
,
Grey
S
, et al
.
Standardized reporting of pulmonary transfusion complications: Development of a model reporting form and flowchart
.
Transfusion
.
2023
;
63
(
6
):
1161
-
1171
.
45.
Proposed Standard Definitions for Surveillance of Non-Infectious Adverse Transfusion Reactions. International Society of Blood Transfusion Working Party on Haemovigilance
. 2011. Accessed 1 July 2011. https://www.isbtweb.org/resource/en-2011-isbt-proposed-standard-definitions-for-surveillance-of-non-infectious-adverse-transfusion-reactions.html.
46.
Khandelwal
A
,
Lin
Y
,
Cserti-Gazdewich
C
, et al
.
TACO-BEL-3: a feasibility study and a retrospective audit of diuretics for patients receiving blood transfusion at ten hospitals
.
Vox Sang
.
2021
;
116
(
4
):
434
-
439
.
47.
Muller
MC
,
van Stein
D
,
Binnekade
JM
,
van Rhenen
DJ
,
Vlaar
AP
.
Low-risk transfusion-related acute lung injury donor strategies and the impact on the onset of transfusion-related acute lung injury: a meta-analysis
.
Transfusion
.
2015
;
55
(
1
):
164
-
175
.
48.
Bolton-Maggs
PHB
.
Serious hazards of transfusion - conference report: celebration of 20 years of UK haemovigilance
.
Transfus Med
.
2017
;
27
(
6
):
393
-
400
.
49.
Eder
AF
,
Herron
RM
,
Strupp
A
, et al
.
Effective reduction of transfusion-related acute lung injury risk with male-predominant plasma strategy in the American Red Cross (2006-2008)
.
Transfusion
.
2010
;
50
(
8
):
1732
-
1742
.
50.
Wiersum-Osselton
JC
,
Middelburg
RA
,
Beckers
EA
, et al
.
Male-only fresh-frozen plasma for transfusion-related acute lung injury prevention: before-and-after comparative cohort study
.
Transfusion
.
2011
;
51
(
6
):
1278
-
1283
.
You do not currently have access to this content.
Sign in via your Institution