YTMRV-50621; No of Pages 7

Transfusion Medicine Reviews xxx (xxxx) xxx

Contents lists available at ScienceDirect

Transfusion Medicine Reviews

journal homepage: https://www.journals.elsevier.com/transfusion-medicine-
reviews/

Near Infrared Spectroscopy in Anemia Detection and Management: A

Systematic Review
Philip Crispin a,b,⁎, Kathryn Forwood c
a
John Curtin School of Medical Research, Australian National University, Acton, ACT, Australia
b
Haematology Department, Canberra Hospital, Garran, ACT, Australia
c
Haematology Department, Dunedin Hospital, Dunedin, New Zealand

a r t i c l e i n f o a b s t r a c t

Available online xxxx Red cell transfusions are intended to improve oxygen delivery to tissues. Although studies comparing hemoglo-
bin concentration triggers for transfusion have been done, the hemoglobin threshold for clinical benefit remains
Keywords: uncertain. Direct measurement of tissue oxygenation with non-invasive near infrared spectroscopy has been
Spectroscopy proposed as a more physiological transfusion trigger, but its clinical role remains unclear. This systematic review
Near infrared examined the role of near infrared spectroscopy for detection of anemia and guiding transfusion decisions.
Blood transfusion
Abstracts were identified up until May 2019 through searches of PubMed, EMBASE and The Web of Science.
Anemia
Hemoglobin
There were 69 studies meeting the inclusion criteria, most (n = 65) of which were observational studies. Tissue
Oxygen oxygen saturation had been measured in a wide range of clinical settings, with neonatal intensive care (n = 26)
and trauma (n = 7) being most common. Correlations with hemoglobin concentration and tissue oxygenation
were noted and there were correlations between changes in red cell mass and changes in tissue oxygenation
through blood loss or transfusion. The value of tissue oxygenation for predicting transfusion was determined
in only four studies, all using muscle oxygen saturation in the adult trauma setting. The overall sensitivity was
low at 34% (27%-42%) and while it had better specificity at 78% (74%-82%), differing and retrospective approaches
create a high level of uncertainty with respect to these conclusions. There were four prospective randomized
studies involving 540 patients, in cardiac and neurological surgery and in neonates that compared near infrared
spectroscopy to guide transfusion decisions with standard practice. These showed a reduction in the number of
red cells transfused per patient (OR: 0.44 [0.09-0.79]), but not the number of patients who received transfusion
(OR: 0.71 [0.46-1.10]), and no change in clinical outcomes. Measuring tissue oxygen saturation has potential to
help guide transfusion; however, there is a lack of data upon which to recommend widespread implementation
into clinical practice. Standardization of measurements is required and greater research into levels at which
tissue oxygenation may lead to adverse clinical outcomes would help in the design of future clinical trials.
© 2020 Elsevier Inc. All rights reserved.

Contents

1. Methods . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0
2. Results . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0
2.1. Neonates . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0
2.2. Trauma . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0
2.3. Pediatrics . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0
2.4. Randomized Trials . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0
2.5. Changes in Hemoglobin . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0
3. Discussion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0
4. Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0
Author Contributions. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0
Conflict of Interest Statement . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0

Abbreviations: AUC, Area under the curve; FTOE, Fractional tissue oxygen extraction; NIRS, Near infrared spectroscopy; SaO2, Arterial oxygen saturation; StO2, Tissue oxygen satura-
tion; tHb, Total hemoglobin.
⁎ Corresponding author at: Philip Crispin, Department of Haematology, Canberra Hospital, PO Box 11, Woden, ACT, Australia 2606.
E-mail address: Philip.crispin@act.gov.au (P. Crispin).

https://doi.org/10.1016/j.tmrv.2020.07.003
0887-7963/© 2020 Elsevier Inc. All rights reserved.

Please cite this article as: P. Crispin and K. Forwood, Near Infrared Spectroscopy in Anemia Detection and Management: A Systematic Review,
Transfusion Medicine Reviews, https://doi.org/10.1016/j.tmrv.2020.07.003
2 P. Crispin, K. Forwood / Transfusion Medicine Reviews xxx (xxxx) xxx

Funding . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0
Appendix A. Supplementary data . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0
Appendix A. Supplementary data . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 0

There have been numerous randomized trials showing equivalence
of restrictive to liberal transfusion strategies based on hemoglobin con-
centrations [1]. While these may indicate when transfusion is unlikely
to help in a particular setting /patient population, there are concerns
about extrapolating the findings to all subpopulations, such as the el-
derly or with concurrent cardiac disease [2]. The studies have also not
defined when transfusion actually improves outcomes [1].
Although transfusion guidance based on hemoglobin concentration is
widely promulgated [3-6], there are difficulties with this approach.
Hemoglobin concentration reflects both the red cell mass and plasma
volume. While restrictive transfusion approaches reduce red cell use [1],
so do restrictive crystalloid protocols, by decreasing the dilutional effect
that may trigger transfusion based on hemoglobin concentration [7].
Hemoglobin concentrations also do not allow for variation in clinical
needs due to patient comorbidities. Alternative approaches to transfusion
triggers could overcome these deficiencies.
Tissue oxygenation measured with near infrared spectroscopy
(NIRS) has been proposed as an alternative aid to transfusion decision
making [8]. Near infrared light can pass deep into tissues. Absorption
and reflection at different wavelengths varies with heme oxygen bind-
ing, so NIRS can measure the principle function of red cells – ensuring
adequate oxygen supply to tissues [9].
The potential benefit of NIRS guided transfusion has been explored in
different settings and previous reviews have considered the role of NIRS
in particular clinical settings [10-13]. However, its role in the detection
of anemia, determining its clinical significance and impact on treatment
decisions has not been previously reviewed. This review sought to deter-
mine the association of NIRS measurements with anemia and its utility in
guiding treatment decisions for anemia, including transfusion.
primary outcomes. Where meta-analysis was performed, a random
effects model was pre-specified.
2. Results
The initial search found 1303 articles, with a further 4 found from
the references of included abstracts. Following exclusions, there were
69 included in the final analyses. The flow diagram of study selection
based on PRISMA guidelines [15] is shown in Fig. 1. The studies were
found to be applicable to the PICO statement, but a majority were at
risk of bias (Supplementary Table 1).
Identified population subgroups for analysis were neonatal (defined
as having been conducted in a neonatal intensive care unit), pediatric
(including children beyond the neonatal period) and adult trauma.
Studies that correlated hemoglobin with NIRS readings were tabulated
and compared, but data were not pooled. There were four randomized
studies [16-19] that compared NIRS-based protocols for transfusion
with standard of care based protocols, which were pooled.
NIRS measurements reported in studies included tissue oxygen sat-
uration (StO2), fractional tissue oxygen extraction (FTOE), total hemo-
globin (tHb) and one study reported on StO2 area under the curve
(AUC) during transfusion with fresh and older blood [20]. FTOE is the
proportion of oxygen extracted from red cells in the tissues. It requires
a known arterial oxygen saturation (SaO2) and is given by the formula
FTOE = (SaO2-StO2)/SaO2. Therefore, the relationship to StO2 is inverse.
The splanchnic / cerebral oxygenation ratio was also reported and
confined to neonatal studies.
2.1. Neonates

1. Methods
A literature search was conducted to find articles related to anemia or
transfusion, and NIRS or tissue oxygen saturation up to May 2019. The
databases searched were the US National Library of Medicine, EMBASE,
Web of Science and the US Clinical trials registry (clinicaltrials.gov).
Opengrey was also searched to find non-indexed studies. The PICO state-
ment is shown in Box 1 and the search strategy outlined in the Supple-
mentary Material. Only studies published in English were included.
Titles and abstracts were reviewed by two authors and selected based
on the PICO criteria to determine the effect of anemia on NIRS parameters
and response to treatment.
Their review followed a prospective (unpublished) study protocol.
Studies were divided into subgroups, based on populations and study
design. Data were extracted to Excel (Microsoft, spreadsheets and ana-
lyzed in Excel spreadsheet (2019, Microsoft, Redmond, WA) and, where
applicable, into RevMan (v5.3 The Nordic Cochrane Centre, Copenhagen).
Studies were reviewed for risk of bias using QUADAS-2 guidelines [14]
and funnel plots were considered where there was a consistently
reported effect measure within similar populations for publication bias.
Qualitative descriptions were performed for all studies and study sub-
groups. The study protocol included quantitative meta-analysis where
studies were of similar design and outcome measures. In these cases,
heterogeneity was assessed using forest plots and studies excluded
from meta-analysis only if outliers had unique features, such as measure-
ment device or population. Although sensitivity analyses were allowed in
the protocol post-hoc to investigate the effect of outliers, these were not
Neonatal intensive care units were the most frequent population
studied, accounting for 26 [19,21-46] of the 69 studies (Supplemen-
tary Table 2). There was one randomized controlled trial [19], three
case–control studies [27,39,44], 21 prospective observational studies
[21-23,25,26,28-31,33-38,40-43,45,46] and one retrospective cohort [32].
The studies included observations related to 1178 blood transfusions, and
one study showed a change in tHb with venesection [33]. There were 13
different NIRS devices used in these studies, including some locally devel-
oped devices. As there is no NIRS standard, this impacts upon the compa-
rability and generalizability of values from individual studies. The sites
examined included cerebral (17 studies), splanchnic (9), muscle (5) and
renal (4) locations.
As the cerebral site was most commonly reported, funnel plots from
the studies that determined whether there was a change in NIRS values
(StO2 and FTOE) with transfusion were constructed to evaluate for po-
tential bias (Supplementary Fig. 1). These suggest the potential for pos-
itive reporting bias, although the absolute number of transfusions in the
larger studies was low (maximum was n = 76).
Of the 24 studies that reported changes with transfusion, 18 demon-
strated an increase in StO2 or a decrease in FTOE following transfusion
[19,21,22,24,26-30,35-39,41,42,45], with a further 3 studies reporting
mixed results between subgroups [32,40,44]. Of the three studies that
reported on a correlation between hemoglobin and NIRS parameters,
two showed a significant correlation [23,42] and one did not [40].
There were two studies suggesting that tissue oxygenation changes
may be associated with a need for transfusion. In the first, neonates with
hemoglobin concentrations in the upper third (above 13.2 g/L) did not
see an improvement in tissue oxygenation found in the lower tertiles.

Please cite this article as: P. Crispin and K. Forwood, Near Infrared Spectroscopy in Anemia Detection and Management: A Systematic Review,
Transfusion Medicine Reviews, https://doi.org/10.1016/j.tmrv.2020.07.003
 P. Crispin, K. Forwood / Transfusion Medicine Reviews xxx (xxxx) xxx 3

Fig. 1. Selection path for studies, following PRISMA reporting guidelines.

[32] Another found a benefit in symptomatic but not asymptomatic ne-
onates [44], where symptoms were prospectively defined as apneas,
frequent bradycardia, tachycardia or poor weight gain, but also included
infants deemed to be pale, generally unwell or lethargic by investiga-
tors. A third study showed no benefit following transfusions based on
physician discretion [19]. The data are conflicted on using NIRS param-
eters to distinguish those that benefit from transfusion from those that
do not. One study suggested the splanchnic / cerebral oxygenation ratio
could be used to predict transfusion need, however this was based on
post-hoc receiver-operator characteristic curve and requires prospec-
tive validation [25].
There was a single neonatal randomized study comparing established
hemoglobin and clinical features-based transfusion thresholds, with
thresholds based on NIRS (FTOE >0.47 with partial venous occlusion)
and hemoglobin concentration [19]. There was no significant difference
in the rate of transfusion, but the study was not blinded to hemoglobin
concentration levels and had a large number of children transfused due
to clinician concern rather than according to the NIRS protocol. It is highly
susceptible to bias and, as noted above, those neonates transfused due to
clinician concern did not show improvements in NIRS parameters seen in
other groups.
2.2. Trauma
There were seven studies, all observational, evaluating transfusion
and NIRS parameters in the trauma setting [20,47-52]. All studies used
peripheral muscle NIRS, with one on the deltoid and the remainder on
thenar muscles (Supplementary Table 3). In this setting, poor tissue

Please cite this article as: P. Crispin and K. Forwood, Near Infrared Spectroscopy in Anemia Detection and Management: A Systematic Review,
Transfusion Medicine Reviews, https://doi.org/10.1016/j.tmrv.2020.07.003
4 P. Crispin, K. Forwood / Transfusion Medicine Reviews xxx (xxxx) xxx
oxygenation may be due to anemia, hypotension or both. The two stud-
ies [49,50] that evaluated the ability of NIRS to predict large volume
transfusion rather than any transfusion are particularly likely to be
confounded. All other studies evaluated the potential for NIRS to predict
any transfusion. Despite using identical instruments, there were differ-
ent StO2 cut-point values used in the studies. This may account for some
of the differences between the observed sensitivities and specificities
(Fig. 2). Three studies [47,48,52] adopted cut-points to determine the
need for any transfusion, whereas one [49] adopted a lower cut-point
to distinguish the need for massive transfusion from any transfusion.
As the latter was the largest study, it brought down the sensitivity for
any transfusion when data were combined, which in the remaining
three studies was over 70%. However, three [47,49,52] of the four stud-
ies that determined the sensitivity and specificity for NIRS measure-
ments (StO2) did so retrospectively and are therefore at high risk of
bias and require prospective validation. The sensitivity and specificity
were not reported for any other studies other than in trauma.
2.3. Pediatrics
There were six pediatric studies identified, with cerebral NIRS
readings reported in five [53-57] and muscle NIRS in two [55,58] (Supple-
mentary Table 4). Response to transfusion was reported in five [53-56,58]
and response to acute normovolemic hemodilution in one [57]. The latter
did not show a significant change in cerebral oxygenation. Of the studies
that reported on a change in StO2 with transfusion, all showed a benefit.
This was very small (0.56%) in a study on patients with extracorporeal
membrane oxygenation who were neither anemic nor had evidence of
impaired oxygenation prior to transfusion [54].
A pre and post implementation study following adoption of a trans-
fusion protocol including NIRS triggers found that transfusion was initi-
ated at higher hemoglobin concentration than prior to NIRS, but with
reduced overall blood use [56]. The study suggests that NIRS may detect
oxygenation change prior to hemoglobin measurement and provide a
degree of reassurance on the safety of hemoglobin levels following
transfusion.
A study involving pediatric oncology outpatients demonstrated a large
absolute increase in StO2 [58]. The observed increase may be largely due
to the lack of confounding factors, such as sickle cell disease or hypoten-
sion impairing perfusion. As the volume of red cells was not clear in
each study, it is uncertain whether higher red cell transfusion volumes
may have contributed, although the hematocrits after transfusion were
not high (26.8–31.8%).
2.4. Randomized Trials
Transfusion based on NIRS or standard of care was assessed in four
randomized controlled trials (Table 1), enrolling 540 patients in cardiac
surgery, [17,18] neurosurgical [16] and neonatal intensive care settings
[19]. While two studies were considered to be of low risk of bias [17,18],
two were at uncertain to high risk of bias due to patient selection or pa-
tient flow, including transfusion off protocol in the NIRS arms [16,45].
The combined outcomes show no significant reduction in the number
of people transfused (Fig. 3) (OR: 0.71 (0.46–1.10)). When only the
two studies judged to be at low risk of bias were included the OR was
0.62 (0.30–1.28). However, where reported the number of red cells
Fig. 2. Sensitivity and specificity of StO2 in predicting the need for transfusion in trauma.
Please cite this article as: P. Crispin and K. Forwood, Near Infrared Spectroscopy in Anemia Detection and Management: A Systematic Review,
Transfusion Medicine Reviews, https://doi.org/10.1016/j.tmrv.2020.07.003
transfused per patient were reduced by a mean of 0.44 (0.09–0.79)
units (Fig. 4). There were no significant differences in clinical endpoints,
including neurocognitive outcomes in one cardiac surgical study [17].
While there was a decrease in the number of red cell units trans-
fused per patient and a trend to a reduction in the number of people
transfused with NIRS-based protocols, the evidence is of low certainty.
2.5. Changes in Hemoglobin
Correlation statistics were reported by nine studies [59-67], with
seven showing significant correlations between hemoglobin concentra-
tion and cerebral StO2 readings (Supplementary Table 5). In addition,
three studies [64–66], all from the same group, reported on correlations
with calf muscle StO2 and showed no significant correlation.
There were 23 studies that reported a change in NIRS parameters
in adults as hemoglobin changed in individuals or across population (Sup-
plementary Table 6) [63-84]. This included 37 analyses in different popu-
lations or at different NIRS sites within the same population. All examined
the change in StO2 as the hemoglobin changed. In 24 analyses there was a
significant increase in StO2 associated with higher hemoglobin levels and
13 showed no improvement. No study showed a negative association
between hemoglobin and StO2. Some also reported on the slopes of
StO2 changes during a vascular occlusion test [28,37,48,52,56] or FTOE
[72,74]. The vascular occlusion test involved a brachial artery tourniquet
maintained above systolic blood pressure to prevent distal blood flow,
typically for 5 minutes or until a pre-determined StO2 threshold
was met, to achieve deoxygenated muscle distally. The rate of fall in
StO2 following occlusion is reported as the downslope and the rate of
rise following tourniquet release as the upslope.
The populations were diverse and included changes due to blood
loss, blood donation or hemodilution, and a variety of devices were
used. Cerebral and muscle sites predominated, with one study using a
sublingual site [85]. Cerebral sites were more likely to show an im-
proved StO2 with increasing hemoglobin than muscle sites and in
seven cohorts where both cerebral and muscle StO2 were measured,
four showed improvement at the cerebral sites without improvement
in muscles [64,65,80,82,84].
StO2 downslope was reported for seven separate populations in five
studies [69-71,77,79], with two comparisons reporting significant
changes, but with opposite effects [70,77]. Upslope changed signifi-
cantly in two [70,71] of the six comparisons, with an increase seen
and the results concordant with StO2.
3. Discussion
There have been prior reviews on the use of NIRS for specific clinical
indications or settings [10,11,13,86]. This review specifically aimed to
address the applicability of NIRS to the detection and impact of anemia,
its ability to detect changes in red cell mass and anemia management
through transfusion.
The optimal transfusion trigger has not yet been defined. While
measurement of tissue oxygenation with NIRS is a rational and easily
accessible test upon which transfusion decisions may be based, this
review has identified a number of barriers to its current use. Among
the studies within this review there was considerable heterogeneity
with respect to the site of NIRS assessment, the clinical settings and
 P. Crispin, K. Forwood / Transfusion Medicine Reviews xxx (xxxx) xxx 5

Table 1
Randomized trials comparing NIRS-based transfusion algorithms with hemoglobin or hematocrit-based triggers

Study N Setting Device Site Comparison Result

Leal-Noval 102 Neurological Invos Cerebral Transfusion with Hb <85 g/L v StO2 <60% 30 (59%) transfused in NIRS v 36 (71%) in Hb based protocol.
2017 ICU P = .15. 1.0 v 1.5 red cells transfused per patient P = .04
[16]
Rogers 204 Cardiac Invos Cerebral Transfusion with Hct <23% vs Cerebral StO2 <50%, <70% No difference in rates of transfusion (38% NIRS v 41%
2017 surgery of baseline levels or Hct <18%. conventional), neurocognitive outcomes, LOS or ICU LOS.
[17]
Vretzakis 150 Cardiac Invos Cerebral StO2 <60% or >20% fall from baseline and low Hct vs low 46 (61%) transfused in NIRS v 55 (73%) in Hct based
2013 surgery Hct only (<21%, but variable target during bypass) protocol. P = .029
[18]
Wardle 74 Neonatal Not Muscle - Transfusion based on standard Hb and symptom protocol Transfused in NIRS = 24 (64%) v 22 (59%). 1.5 v 2.3 red
2002 intensive stated forearm or FTOE >47% during partial venous occlusion study cells transfused per patient P = .64
[19] care

Abbreviations: FTOE, fractional tissue oxygen extraction; Hb, hemoglobin; Hct, hematocrit; ICU, intensive care; LOS, Length of stay; NIRS, near infrared spectroscopy.

the instruments used. Devices may use different wavelengths, focus on
different tissue depths and use different algorithms to determine StO2.
There is no standard against which they can be measured and compar-
ison using a phantom has highlighted the variation between instru-
ments [87]. Even among the studies that determined a sensitivity and
specificity for NIRS parameters for transfusion, which all used an identi-
cal instrument within the one setting (trauma), there was variation in
the cut-off values determined to predict the need for transfusion.
The majority of studies were observational and without already ac-
cepted widespread indications for transfusion, it is difficult to establish
that NIRS provides a more useful trigger than currently available ap-
proaches to transfusion. No studies examined at what point adverse
anemia-related clinical consequences, other than transfusion, were pre-
dicted by NIRS.
Overall, the data favor a correlation with higher hemoglobin and
improved StO2. This effect was apparent even when the changes in hemo-
globin were within the normal range, such as blood donors, and suggest
that increasing oxygenation may rise as a continuous variable with hemo-
globin, at least within the range of hemoglobin included in these studies.
A StO2 threshold for transfusion has not been defined, as is still the case
for hemoglobin concentration; however this is more difficult with NIRS
owing to the lack of standardization.
The randomized controlled trials that used NIRS-based transfusion
protocols suggested a reduction in the number of red cells transfused.
However, the included studies were of mixed methodological quality
and this finding may be subject to bias and this finding is therefore
made with low confidence.
The predominance of NIRS measurements in neonatal, pediatric,
intensive care and surgical settings may reflect a need to obtain better
information on the circulation in patients unable to communicate. This
would be a useful indication for the test, but in this setting there is a
high potential for factors, including hypotension or redistribution of
microvascular flow due to systemic inflammation or vasoactive medica-
tions, to confound the role of NIRS in anemia assessment. Furthermore,
in this setting correlation with patient symptoms is often not possible.
4. Conclusion
This review shows that there is a correlation between NIRS detected
parameters and hemoglobin concentration. These parameters have the
potential to identify changes in red cell mass through bleeding, hemodi-
lution or transfusion and may reduce the amount of blood transfused
when used as part of transfusion protocols. However, these findings
are made with a low level of confidence. When combined with a lack
of standardization of instruments, no defined transfusion threshold
and the confounding effect of concurrent illness and therapies, there
are insufficient data to support routine application of NIRS in transfu-
sion decisions. Further research should consider whether there is a
threshold for NIRS parameters and adverse anemia related outcomes
that may serve as a transfusion trigger. These may be best performed
in hemodynamically stable patients to avoid the effect of comorbid
conditions.
Author Contributions
PC conceived and designed the study, conducted review and data
analysis, wrote and approved the manuscript.
KF approved the study design, conducted review, and wrote and ap-
proved the manuscript.
Conflict of Interest Statement
The authors declare that they have no conflicts of interest in relation
to this work.
Funding
PC has received funding from the Australian Government Research
Training Scholarship and the Australian National University College of
Health and Medicine.

Fig. 3. Forest plot of randomized controlled trials comparing NIRS-based transfusion protocols with standard of care protocols.

Please cite this article as: P. Crispin and K. Forwood, Near Infrared Spectroscopy in Anemia Detection and Management: A Systematic Review,
Transfusion Medicine Reviews, https://doi.org/10.1016/j.tmrv.2020.07.003
6 P. Crispin, K. Forwood / Transfusion Medicine Reviews xxx (xxxx) xxx
Fig. 4. Forest plot of randomized controls trials of NIRs compared with standard of care, number of transfusions per patient.
Appendix A. Supplementary data
Supplementary data to this article can be found online at https://doi.
org/10.1016/j.tmrv.2020.07.003.
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