Abstract

A recent Perspective in Blood suggested that previous evidence from over a decade ago established that a liberal rather than a restrictive blood transfusion strategy results in better outcomes in patients with anemia and either acute myocardial infarction or stable cardiovascular disease. Their premise was that physiological evidence, and a different interpretation of the Transfusion Requirements in Critical Care (TRICC) trial should have been sufficient to establish clinical practice. They also suggest that a more personalized approach to the administration of transfusions would have been made possible by including a usual-care arm in all transfusion trials. In this counterpoint Perspective, we describe how and why 2 discrete and common blood transfusion thresholds were selected in the TRICC, FOCUS, REALITY, and MINT trials. We explain why a usual-care arm would have been uninformative. We also propose that we still do not have evidence to provide firm transfusion recommendations in several specific subpopulations of patients, including those with stable atherosclerotic coronary artery disease. Finally, we provide our perspective on the state of existing evidence and on the clinical recommendations that should be adopted in practice.

1.
Natanson
C
,
Applefeld
WN
,
Klein
HG
.
Hemoglobin-based transfusion strategies for cardiovascular and other diseases: restrictive, liberal, or neither?
.
Blood
.
2024
;
144
(
20
):
2075
-
2082
.
2.
Hebert
PC
,
Wells
G
,
Blajchman
MA
, et al
.
A multicenter, randomized, controlled clinical trial of transfusion requirements in critical care. Transfusion requirements in critical care investigators, Canadian Critical Care Trials Group
.
New Engl J Med
.
1999
;
340
(
6
):
409
-
417
.
3.
Carson
JL
,
Terrin
ML
,
Noveck
H
, et al
.
Liberal or restrictive transfusion in high-risk patients after hip surgery
.
N Engl J Med
.
2011
;
365
(
26
):
2453
-
2462
.
4.
Ducrocq
G
,
Gonzalez-Juanatey
JR
,
Puymirat
E
, et al
.
Effect of a restrictive vs liberal blood transfusion strategy on major cardiovascular events among patients with acute myocardial infarction and anemia: the REALITY randomized clinical trial
.
JAMA
.
2021
;
325
(
6
):
552
-
560
.
5.
Carson
JL
,
Brooks
MM
,
Hébert
PC
, et al
.
Restrictive or liberal transfusion strategy in myocardial infarction and anemia
.
N Engl J Med
.
2023
;
389
(
26
):
2446
-
2456
.
6.
Gonzalez-Juanatey
JR
,
Lemesle
G
,
Puymirat
E
, et al
.
One-year major cardiovascular events after restrictive versus liberal blood transfusion strategy in patients with acute myocardial infarction and anemia: the REALITY randomized trial
.
Circulation
.
2022
;
145
(
6
):
486
-
488
.
7.
Alexander
JH
.
Equipoise in clinical trials: enough uncertainty in whose opinion?
.
Circulation
.
2022
;
145
(
13
):
943
-
945
.
8.
Hébert
PC
,
Wells
G
,
Martin
C
, et al
.
A Canadian survey of transfusion practices in critically ill patients. Transfusion requirements in critical care investigators and the Canadian Critical Care Trials Group
.
Crit Care Med
.
1998
;
26
(
3
):
482
-
487
.
9.
Rao
SV
,
Jollis
JG
,
Harrington
RA
, et al
.
Relationship of blood transfusion and clinical outcomes in patients with acute coronary syndromes
.
J Am Med Assoc
.
2004
;
292
(
13
):
1555
-
1562
.
10.
Consensus conference. Perioperative red blood cell transfusion
.
J Am Med Assoc
.
1988
;
260
(
18
):
2700
-
2703
.
11.
Ducrocq
G
,
Calvo
G
,
González-Juanatey
JR
, et al
.
Restrictive vs liberal red blood cell transfusion strategies in patients with acute myocardial infarction and anemia: rationale and design of the REALITY trial
.
Clin Cardiol
.
2021
;
44
(
2
):
143
-
150
.
12.
Carson
JL
,
Brooks
MM
,
Chaitman
BR
, et al
.
Rationale and design for the myocardial ischemia and transfusion (MINT) randomized clinical trial
.
Am Heart J
.
2023
;
257
:
120
-
129
.
13.
Hébert
PC
,
Fergusson
D
,
Blajchman
MA
, et al
.
Clinical outcomes following institution of the Canadian universal leukoreduction program for red blood cell transfusions
.
J Am Med Assoc
.
2003
;
289
(
15
):
1941
-
1949
.
14.
Carson
JL
,
Terrin
ML
,
Barton
FB
, et al
.
A pilot randomized trial comparing symptomatic vs. hemoglobin-level-driven red blood cell transfusions following hip fracture
.
Transfusion
.
1998
;
38
(
6
):
522
-
529
.
15.
Carson
JL
,
Brooks
MM
,
Abbott
JD
, et al
.
Liberal versus restrictive transfusion thresholds for patients with symptomatic coronary artery disease
.
Am Heart J
.
2013
;
165
(
6
):
964
-
971.e1
.
16.
Applefeld
WN
,
Wang
J
,
Klein
HG
,
Danner
RL
,
Eichacker
PQ
,
Natanson
C
.
Comparative effectiveness research in critically ill patients: risks associated with mischaracterising usual care
.
Crit Care Resusc
.
2020
;
22
(
2
):
110
-
118
.
17.
Cortés-Puch
I
,
Wesley
RA
,
Carome
MA
,
Danner
RL
,
Wolfe
SM
,
Natanson
C
.
Usual care and informed consent in clinical trials of oxygen management in extremely premature infants
.
PLoS One
.
2016
;
11
(
5
):
e0155005
.
18.
Deans
KJ
,
Minneci
PC
,
Danner
RL
,
Eichacker
PQ
,
Natanson
C
.
Practice misalignments in randomized controlled trials: identification, impact, and potential solutions
.
Anesth Analg
.
2010
;
111
(
2
):
444
-
450
.
19.
Carson
JL
,
Stanworth
SJ
,
Dennis
JA
, et al
.
Transfusion thresholds for guiding red blood cell transfusion
.
Cochrane Database Syst Rev
.
2021
;
12
(
12
):
CD002042
.
20.
Tucci MDP-T
G
,
Leteurtre
S
,
Ray
S
, et al
.
A pilot randomized controlled trial to organize OpTTICCA, which will be a large international trial on the efficacy and safety of a low hemoglobin threshold to guide red blood cell transfusions in almost all anemic critically ill children
.
Ann Intensive Care
.
2023
;
11
:
FC-226
.
21.
Vuille-Lessard
E
,
Boudreault
D
,
Girard
F
,
Ruel
M
,
Chagnon
M
,
Hardy
JF
.
Red blood cell transfusion practice in elective orthopedic surgery: a multicenter cohort study
.
Transfusion
.
2010
;
50
(
10
):
2117
-
2124
.
22.
Carling
MS
,
Jeppsson
A
,
Eriksson
BI
,
Brisby
H
.
Transfusions and blood loss in total hip and knee arthroplasty: a prospective observational study
.
J Orthop Surg Res
.
2015
;
10
:
48
.
23.
Bracey
AW
,
Radovancevic
R
,
Riggs
SA
, et al
.
Lowering the hemoglobin threshold for transfusion in coronary artery bypass procedures: effect on patient outcome
.
Transfusion
.
1999
;
39
(
10
):
1070
-
1077
.
24.
Hajjar
LA
,
Vincent
JL
,
Galas
FR
, et al
.
Transfusion requirements after cardiac surgery: the TRACS randomized controlled trial
.
JAMA
.
2010
;
304
(
14
):
1559
-
1567
.
25.
Johnson
RG
,
Thurer
RL
,
Kruskall
MS
, et al
.
Comparison of two transfusion strategies after elective operations for myocardial revascularization
.
J Thorac Cardiovasc Surg
.
1992
;
104
(
2
):
307
-
314
.
26.
Koch
CG
,
Sessler
DI
,
Mascha
EJ
, et al
.
A randomized clinical trial of red blood cell transfusion triggers in cardiac surgery
.
Ann Thorac Surg
.
2017
;
104
(
4
):
1243
-
1250
.
27.
Laine
A
,
Niemi
T
,
Schramko
A
.
Transfusion threshold of hemoglobin 80 g/L is comparable to 100 g/L in terms of bleeding in cardiac surgery: a prospective randomized study
.
J Cardiothorac Vasc Anesth
.
2018
;
32
(
1
):
131
-
139
.
28.
Mazer
CD
,
Whitlock
RP
,
Fergusson
DA
, et al
.
Restrictive or liberal red-cell transfusion for cardiac surgery
.
N Engl J Med
.
2017
;
377
(
22
):
2133
-
2144
.
29.
Murphy
GJ
,
Pike
K
,
Rogers
CA
, et al
.
Liberal or restrictive transfusion after cardiac surgery
.
N Engl J Med
.
2015
;
372
(
11
):
997
-
1008
.
30.
Shehata
N
,
Burns
LA
,
Nathan
H
, et al
.
A randomized controlled pilot study of adherence to transfusion strategies in cardiac surgery
.
Transfusion
.
2012
;
52
(
1
):
91
-
99
.
31.
Carson
JL
,
Brooks
MM
,
Hebert
PC
.
Transfusion strategy in myocardial infarction and anemia. Reply
.
N Engl J Med
.
2024
;
390
(
10
):
961
-
962
.
32.
Chapalain
X
,
Aubron
C
.
Transfusion strategy in myocardial infarction and anemia
.
N Engl J Med
.
2024
;
390
(
10
):
960
.
33.
Khan
MS
,
Spertus
JA
,
Chan
PS
.
Transfusion strategy in myocardial infarction and anemia
.
N Engl J Med
.
2024
;
390
(
10
):
960
-
961
.
34.
Applefeld
WN
,
Ford
VJ
,
Cortes-Puch
I
, et al
.
Risks of restrictive versus liberal red blood cell transfusion strategies in patients with cardiovascular disease: an updated meta-analysis
.
Circ Cardiovasc Qual Outcomes
.
2024
;
17
(
6
):
e010957
.
35.
Idowu
A
,
Lo
K
,
Adebolu
O
,
Ibe
F
,
Al-Madani
M
.
Outcomes of restrictive versus liberal blood transfusion in patients with acute myocardial infarction and anemia: an updated meta-analysis of randomized controlled trials
.
Am J Cardiol
.
2024
;
212
:
48
-
50
.
36.
Mistry
N
,
Hare
GMT
,
Shehata
N
, et al
.
Transfusion thresholds for acute coronary syndromes-insights from the TRICS-III randomized controlled trial, systematic review, and meta-analysis
.
J Am Heart Assoc
.
2023
;
12
(
1
):
e028497
.
37.
Carson
JL FDA
,
Noveck
H
,
Mallick
R
.
Restrictive versus liberal transfusion in myocardial infarction - a patient level meta-analysis
.
NEJM Evid
.
2025
;
4
(
2
):
EVIDoa2400223
.
38.
Bush
RL
,
Pevec
WC
,
Holcroft
JW
.
A prospective, randomized trial limiting perioperative red blood cell transfusions in vascular patients
.
Am J Surg
.
1997
;
174
(
2
):
143
-
148
.
39.
Parker
MJ
.
Randomised trial of blood transfusion versus a restrictive transfusion policy after hip fracture surgery
.
Injury
.
2013
;
44
(
12
):
1916
-
1918
.
40.
Guyatt
GH
,
Oxman
AD
,
Santesso
N
, et al
.
GRADE guidelines: 12. Preparing summary of findings tables-binary outcomes
.
J Clin Epidemiol
.
2013
;
66
(
2
):
158
-
172
.
41.
Guyatt
GH
,
Oxman
AD
,
Schünemann
HJ
,
Tugwell
P
,
Knottnerus
A
.
GRADE guidelines: a new series of articles in the Journal of Clinical Epidemiology
.
J Clin Epidemiol
.
2011
;
64
(
4
):
380
-
382
.
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