Severe anemia is commonly treated with red blood cell transfusion. Clinical trials have demonstrated that a restrictive transfusion strategy of 7 to 8 g/dL is as safe as a liberal transfusion strategy of 9 to 10 g/dL in many clinical settings. Evidence is lacking for subgroups of patients, including those with preexisting coronary artery disease, acute myocardial infarction, congestive heart failure, and myelodysplastic neoplasms. We present 3 clinical vignettes that highlight the clinical challenges in caring for patients with coronary artery disease with gastrointestinal bleeding, congestive heart failure, or myelodysplastic neoplasms. We emphasize that transfusion practice should be guided by patient symptoms and preferences in conjunction with the patient’s hemoglobin concentration. Along with the transfusion decision, evaluation and management of the etiology of the anemia is essential. Iron-restricted erythropoiesis is a common cause of anemia severe enough to be considered for red blood cell transfusion but diagnosis and management of absolute iron deficiency anemia, the anemia of inflammation with functional iron deficiency, or their combination may be problematic. Intravenous iron therapy is generally the treatment of choice for absolute iron deficiency in patients with complex medical disorders, with or without coexisting functional iron deficiency.

1.
Carson
JL
,
Guyatt
G
,
Heddle
NM
, et al
.
Clinical practice guidelines from the AABB: red blood cell transfusion thresholds and storage
.
JAMA
.
2016
. ;
316
(
19
):
2025
-
2035
.
2.
Mueller
MM
,
Van Remoortel
H
,
Meybohm
P
, et al
.
Patient blood management: recommendations from the 2018 Frankfurt consensus conference
.
JAMA
.
2019
. ;
321
(
10
):
983
-
997
.
3.
Carson
JL
,
Stanworth
SJ
,
Dennis
JA
, et al
.
Transfusion thresholds for guiding red blood cell transfusion
.
Cochrane Database Syst Rev
.
2021
. (
12
):
CD002042
.
4.
Josephson
C
.
Anemia measures and RBC transfusion decision making. National Heart Lung Blood Institute
. Accessed 29 August 2022. https://videocast.nih.gov/watch=46107.
5.
Camaschella
C
,
Pagani
A
,
Silvestri
L
,
Nai
A
.
The mutual crosstalk between iron and erythropoiesis
.
Int J Hematol
.
2022
. ;
116
(
2
):
182
-
191
.
6.
Marques
O
,
Weiss
G
,
Muckenthaler
MU
.
The role of iron in chronic inflammatory diseases: from mechanisms to treatment options in anemia of inflammation
.
Blood
.
2022
. ;
140
(
19
):
2011
-
2023
.
7.
Nemeth
E
,
Ganz
T
.
Hepcidin and iron in health and disease
.
Annu Rev Med
.
2023
. ;
74
:
261
-
277
.
8.
Koleini
N
,
Shapiro
JS
,
Geier
J
,
Ardehali
H
.
Ironing out mechanisms of iron homeostasis and disorders of iron deficiency
.
J Clin Invest
.
2021
. ;
131
(
11
):
e148671
.
9.
Pasricha
SR
,
Tye-Din
J
,
Muckenthaler
MU
,
Swinkels
DW
.
Iron deficiency
.
Lancet
.
2021
. ;
397
(
10270
):
233
-
248
.
10.
Coffey
R
,
Jung
G
,
Olivera
JD
, et al
.
Erythroid overproduction of erythroferrone causes iron overload and developmental abnormalities in mice
.
Blood
.
2022
. ;
139
(
3
):
439
-
451
.
11.
Kautz
L
,
Jung
G
,
Valore
EV
,
Rivella
S
,
Nemeth
E
,
Ganz
T
.
Identification of erythroferrone as an erythroid regulator of iron metabolism
.
Nat Genet
.
2014
. ;
46
(
7
):
678
-
684
.
12.
Gattermann
N
,
Muckenthaler
MU
,
Kulozik
AE
,
Metzgeroth
G
,
Hastka
J
.
The evaluation of iron deficiency and iron overload
.
Dtsch Arztebl Int
.
2021
. ;
118
(
49
):
847
-
856
.
13.
Villanueva
C
,
Colomo
A
,
Bosch
A
, et al
.
Transfusion strategies for acute upper gastrointestinal bleeding
.
N Engl J Med
.
2013
. ;
368
(
1
):
11
-
21
.
14.
Odutayo
A
,
Desborough
MJ
,
Trivella
M
, et al
.
Restrictive versus liberal blood transfusion for gastrointestinal bleeding: a systematic review and meta-analysis of randomised controlled trials
.
Lancet Gastroenterol Hepatol
.
2017
. ;
2
(
5
):
354
-
360
.
15.
Carson
JL
,
Duff
A
,
Poses
RM
, et al
.
Effect of anaemia and cardiovascular disease on surgical mortality and morbidity
.
Lancet
.
1996
. ;
348
(
9034
):
1055
-
1060
.
16.
Anderson
HT
,
Kessinger
JM
,
McFarland
WJ
,
Laks
H
,
Geha
AS
.
Response of the hypertrophied heart to acute anemia and coronary stenosis
.
Surgery
.
1978
. ;
84
(
1
):
8
-
15
.
17.
Hagl
S
,
Heimisch
W
,
Meisner
H
,
Erben
R
,
Baum
M
,
Mendler
N
.
The effect of hemodilution on regional myocardial function in the presence of coronary stenosis
.
Basic Res Cardiol
.
1977
. ;
72
(
4
):
344
-
364
.
18.
Wilkerson
DK
,
Rosen
AL
,
Sehgal
LR
,
Gould
SA
,
Sehgal
HL
,
Moss
GS
.
Limits of cardiac compensation in anemic baboons
.
Surgery
.
1988
. ;
103
(
6
):
665
-
670
.
19.
Hajjar
LA
,
Vincent
JL
,
Galas
FR
, et al
.
Transfusion requirements after cardiac surgery: the TRACS randomized controlled trial
.
JAMA
.
2010
. ;
304
(
14
):
1559
-
1567
.
20.
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
.
21.
Murphy
GJ
,
Pike
K
,
Rogers
CA
, et al
.
Liberal or restrictive transfusion after cardiac surgery
.
N Engl J Med
.
2015
. ;
372
(
11
):
997
-
1008
.
22.
Mazer
CD
,
Whitlock
RP
,
Fergusson
DA
, et al
.
Six-month outcomes after restrictive or liberal transfusion for cardiac surgery
.
N Engl J Med
.
2018
. ;
379
(
13
):
1224
-
1233
.
23.
Mazer
CD
,
Whitlock
RP
,
Fergusson
DA
, et al
.
Restrictive or liberal red-cell transfusion threshold for cardiac surgery
.
N Engl J Med
.
2017
. ;
377
(
22
):
2133
-
2144
.
24.
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
.
25.
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
.
26.
Moller
A
,
Nielsen
HB
,
Wetterslev
J
, et al
.
Low vs high hemoglobin trigger for transfusion in vascular surgery: a randomized clinical feasibility trial
.
Blood
.
2019
. ;
133
(
25
):
2639
-
2650
.
27.
Grover
M
,
Talwalkar
S
,
Casbard
A
, et al
.
Silent myocardial ischaemia and haemoglobin concentration: a randomized controlled trial of transfusion strategy in lower limb arthroplasty
.
Vox Sang
.
2006
. ;
90
(
2
):
105
-
112
.
28.
Walsh
TS
,
Boyd
JA
,
Watson
D
, et al
.
Restrictive versus liberal transfusion strategies for older mechanically ventilated critically ill patients: a randomized pilot trial
.
Crit Care Med
.
2013
. ;
41
(
10
):
2354
-
2363
.
29.
Cortes-Puch
I
,
Wiley
BM
,
Sun
J
, et al
.
Risks of restrictive red blood cell transfusion strategies in patients with cardiovascular disease (CVD): a meta-analysis
.
Transfus Med
.
2018
. ;
28
(
5
):
335
-
345
.
30.
Docherty
AB
,
O'Donnell
R
,
Brunskill
S
, et al
.
Effect of restrictive versus liberal transfusion strategies on outcomes in patients with cardiovascular disease in a non-cardiac surgery setting: systematic review and meta-analysis
.
BMJ
.
2016
. ;
352
:
i1351
.
31.
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
.
32.
Cooper
HA
,
Rao
SV
,
Greenberg
MD
, et al
.
Conservative versus liberal red cell transfusion in acute myocardial infarction (the CRIT Randomized Pilot Study)
.
Am J Cardiol
.
2011
. ;
108
(
8
):
1108
-
1111
.
33.
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
.
34.
Myocardial ischemia and transfusion (MINT)
.
ClinicalTrials.gov identifier NCT02981407
. Accessed 14 November 2022. https://clinicaltrials.gov/ct2/show/NCT02981407.
35.
El-Halabi
MM
,
Green
MS
,
Jones
C
,
Salyers
WJ
.
Under-diagnosing and under-treating iron deficiency in hospitalized patients with gastrointestinal bleeding
.
World J Gastrointest Pharmacol Ther
.
2016
. ;
7
(
1
):
139
-
144
.
36.
Bager
P
,
Dahlerup
JF
.
Randomised clinical trial: oral vs. intravenous iron after upper gastrointestinal haemorrhage--a placebo-controlled study
.
Aliment Pharmacol Ther
.
2014
. ;
39
(
2
):
176
-
187
.
37.
Shah
AA
,
Donovan
K
,
Seeley
C
, et al
.
Risk of infection associated with administration of intravenous iron: a systematic review and meta-analysis
.
JAMA Netw Open
.
2021
. ;
4
(
11
):
e2133935
.
38.
Dave
CV
,
Brittenham
GM
,
Carson
JL
,
Setoguchi
S
.
Risks for anaphylaxis with intravenous iron formulations: a retrospective cohort study
.
Ann Intern Med
.
2022
. ;
175
(
5
):
656
-
664
.
39.
Rund
D
.
Intravenous iron: do we adequately understand the short- and long-term risks in clinical practice?
.
Br J Haematol
.
2021
. ;
193
(
3
):
466
-
480
.
40.
Roubinian
NH
,
Hendrickson
JE
,
Triulzi
DJ
, et al
.
Incidence and clinical characteristics of transfusion-associated circulatory overload using an active surveillance algorithm
.
Vox Sang
.
2017
. ;
112
(
1
):
56
-
63
.
41.
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
.
42.
Chopra
VK
,
Anker
SD
.
Anaemia, iron deficiency and heart failure in 2020: facts and numbers
.
ESC Heart Fail
.
2020
. ;
7
(
5
):
2007
-
2011
.
43.
Migone de Amicis
M
,
Chivite
D
,
Corbella
X
,
Cappellini
MD
,
Formiga
F
.
Anemia is a mortality prognostic factor in patients initially hospitalized for acute heart failure
.
Intern Emerg Med
.
2017
. ;
12
(
6
):
749
-
756
.
44.
Swedberg
K
,
Young
JB
,
Anand
IS
, et al
.
Treatment of anemia with darbepoetin alfa in systolic heart failure
.
N Engl J Med
.
2013
. ;
368
(
13
):
1210
-
1219
.
45.
Avni
T
,
Bieber
A
,
Grossman
A
,
Green
H
,
Leibovici
L
,
Gafter-Gvili
A
.
The safety of intravenous iron preparations: systematic review and meta-analysis
.
Mayo Clin Proc
.
2015
. ;
90
(
1
):
12
-
23
.
46.
Yamani
N
,
Ahmed
A
,
Gosain
P
, et al
.
Effect of iron supplementation in patients with heart failure and iron deficiency: a systematic review and meta-analysis
.
Int J Cardiol Heart Vasc
.
2021
. ;
36
:
100871
.
47.
Lewis
GD
,
Malhotra
R
,
Hernandez
AF
, et al
.
Effect of oral iron repletion on exercise capacity in patients with heart failure with reduced ejection fraction and iron deficiency: the IRONOUT HF Randomized Clinical Trial
.
JAMA
.
2017
. ;
317
(
19
):
1958
-
1966
.
48.
Heidenreich
PA
,
Bozkurt
B
,
Aguilar
D
, et al
.
2022 AHA/ACC/HFSA guideline for the management of heart failure: a report of the American College of Cardiology/American Heart Association Joint Committee on clinical practice guidelines
.
J Am Coll Cardiol
.
2022
. ;
79
(
17
):
e263
-
e421
.
49.
McDonagh
TA
,
Metra
M
,
Adamo
M
, et al
.
2021 ESC guidelines for the diagnosis and treatment of acute and chronic heart failure: developed by the Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC). With the special contribution of the Heart Failure Association (HFA) of the ESC
.
Eur J Heart Fail
.
2022
. ;
24
(
1
):
4
-
131
.
50.
Anand
I
,
Gupta
P
.
How I treat anemia in heart failure
.
Blood
.
2020
. ;
136
(
7
):
790
-
800
.
51.
Grote Beverborg
N
,
Klip
IT
,
Meijers
WC
, et al
.
Definition of iron deficiency based on the gold standard of bone marrow iron staining in heart failure patients
.
Circ Heart Fail
.
2018
. ;
11
(
2
):
e004519
.
52.
Cuthbert
JJ
,
Ransome
N
,
Clark
AL
.
Re-defining iron deficiency in patients with heart failure
.
Expert Rev Cardiovasc Ther
.
2022
. ;
20
(
8
):
667
-
681
.
53.
Campodonico
J
,
Nicoli
F
,
Motta
I
, et al
.
Prognostic role of transferrin saturation in heart failure patients
.
Eur J Prev Cardiol
.
2021
. ;
28
(
15
):
1639
-
1646
.
54.
Gentil
JRS
,
Fabricio
CG
,
Tanaka
DM
, et al
.
Should we use ferritin in the diagnostic criteria of iron deficiency in heart failure patients?
.
Clin Nutr ESPEN
.
2020
. ;
39
:
119
-
123
.
55.
Martens
P
,
Grote Beverborg
N
,
van der Meer
P
.
Iron deficiency in heart failure-time to redefine
.
Eur J Prev Cardiol
.
2021
. ;
28
(
15
):
1647
-
1649
.
56.
Masini
G
,
Graham
FJ
,
Pellicori
P
, et al
.
Criteria for iron deficiency in patients with heart failure
.
J Am Coll Cardiol
.
2022
. ;
79
(
4
):
341
-
351
.
57.
Grote Beverborg
N
,
van der Wal
HH
,
Klip
IT
, et al
.
Differences in clinical profile and outcomes of low iron storage vs defective iron utilization in patients with heart failure: results from the DEFINE-HF and BIOSTAT-CHF studies
.
JAMA Cardiol
.
2019
. ;
4
(
7
):
696
-
701
.
58.
Cercamondi
CI
,
Stoffel
NU
,
Moretti
D
, et al
.
Iron homeostasis during anemia of inflammation: a prospective study of patients with tuberculosis
.
Blood
.
2021
. ;
138
(
15
):
1293
-
1303
.
59.
van Dalen
DH
,
Kragten
JA
,
Emans
ME
, et al
.
Acute heart failure and iron deficiency: a prospective, multicentre, observational study
.
ESC Heart Fail
.
2022
. ;
9
(
1
):
398
-
407
.
60.
Alnuwaysir
RIS
,
Grote Beverborg
N
,
van der Meer
P
.
Fluctuating iron levels in heart failure: when and where to look at?
.
Eur J Heart Fail
.
2022
. ;
24
(
5
):
818
-
820
.
61.
Greenberg
PL
,
Stone
RM
,
Al-Kali
A
, et al
.
NCCN Guidelines® insights: myelodysplastic syndromes, version 3.2022
.
J Natl Compr Canc Netw
.
2022
. ;
20
(
2
):
106
-
117
.
62.
Wood
EM
,
McQuilten
ZK
.
Outpatient transfusions for myelodysplastic syndromes
.
Hematology Am Soc Hematol Educ Program
.
2020
. ;
2020
(
1
):
167
-
174
.
63.
Stanworth
SJ
,
Killick
S
,
McQuilten
ZK
, et al
.
Red cell transfusion in outpatients with myelodysplastic syndromes: a feasibility and exploratory randomised trial
.
Br J Haematol
.
2020
. ;
189
(
2
):
279
-
290
.
64.
Jansen
AJG
,
van den Bosch
J
,
Te Boekhorst
PAW
,
Schipperus
MR
,
Beckers
EAM
.
Results of the prematurely terminated TEMPLE randomized controlled trial in patients with myelodysplastic syndrome: liberal versus restrictive red blood cell transfusion threshold
.
Transfusion
.
2020
. ;
60
(
4
):
879
-
881
.
65.
Mo
A
,
McQuilten
ZK
,
Wood
EM
,
Weinkove
R
.
Red cell transfusion thresholds in myelodysplastic syndromes: a clinician survey to inform future clinical trials
.
Intern Med J
.
2017
. ;
47
(
6
):
695
-
698
.
66.
Hoeks
MPA
,
Middelburg
RA
,
Romeijn
B
,
Blijlevens
NMA
,
van Kraaij
MGJ
,
Zwaginga
JJ
.
Red blood cell transfusion support and management of secondary iron overload in patients with haematological malignancies in the Netherlands: a survey
.
Vox Sang
.
2018
. ;
113
(
2
):
152
-
159
.
67.
Balitsky
A
,
Arnold
D
.
Transfusion thresholds in myelodysplastic syndrome-helping patients live better
.
Transfusion
.
2022
. ;
62
(
7
):
1313
-
1314
.
68.
Vijenthira
A
,
Starkman
R
,
Lin
Y
, et al
.
Multi-national survey of transfusion experiences and preferences of patients with myelodysplastic syndrome
.
Transfusion
.
2022
. ;
62
(
7
):
1355
-
1364
.
69.
Chhetri
R
,
Wee
LYA
,
Sinha
R
, et al
.
Red cell autoimmunization and alloimmunization in myelodysplastic syndromes: prevalence, characteristic and significance
.
Haematologica
.
2019
. ;
104
(
10
):
e451
-
e454
.
70.
Singhal
D
,
Kutyna
MM
,
Chhetri
R
, et al
.
Red cell alloimmunization is associated with development of autoantibodies and increased red cell transfusion requirements in myelodysplastic syndrome
.
Haematologica
.
2017
. ;
102
(
12
):
2021
-
2029
.
71.
Karafin
MS
,
Westlake
M
,
Hauser
RG
, et al
.
Risk factors for red blood cell alloimmunization in the Recipient Epidemiology and Donor Evaluation Study (REDS-III) database
.
Br J Haematol
.
2018
. ;
181
(
5
):
672
-
681
.
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