Patient Blood Management

E   Original Clinical Research Report

Ratios of Plasma and Platelets to Red Blood Cells

in Surgical Patients With Acute Intraoperative
Hemorrhage
Matthew A. Warner, MD,* Ryan D. Frank, MS,† Timothy J. Weister, MSN, RN,* Nageswar R. Madde,
MS,* Ognjen Gajic, MD,‡ and Daryl J. Kor, MD*

BACKGROUND: The relationships between the ratios of transfused allogeneic blood products
and clinical outcomes in patients with acute intraoperative hemorrhage are poorly defined.
METHODS: To better define these ratios, we undertook a single-center, observational cohort
study of all surgical patients (≥18 years) who received rapid transfusion defined by a critical
administration threshold of 3 or more units of red blood cells (RBCs) intraoperatively within 1
hour between January 1, 2011 and December 31, 2015. Multivariable regression analyses were
used to assess relationships between ratios of plasma to RBCs and platelets to RBCs at 3, 12,
and 24 hours and clinical outcomes. The primary outcome was hospital mortality, with second-
ary outcomes of intensive care unit and hospital-free days.
RESULTS: The study included 2385 patients, of whom 14.9% had a plasma-to-RBC ratio of
1.0+, and 47.6% had a platelet-to-RBC ratio of 1.0+. Higher plasma-to-RBC and platelet-to-
RBC ratios were observed for patients who underwent cardiac, transplant, and vascular surgery
and in patients with greater derangements in hemostatic laboratory values. Ratios did not
differ by patient age or severity of illness. Higher ratios were not associated with improved
clinical outcomes. Mortality differed by platelet-to-RBC but not plasma-to-RBC ratio, with the
highest mortality observed with a platelet-to-RBC ratio of 0.1–0.9 at 24 hours (odds ratio, 3.34
[1.62–6.88]) versus no platelets (P = .001). Higher plasma-to-RBC ratios were associated with
decreased hospital-free days, although differences in clinical outcomes were not significant
after exclusion of patients receiving only RBCs without component therapies.
CONCLUSIONS: Transfusion ratios in surgical patients with critical intraoperative hemor-
rhage were largely related to surgical and hemostatic features rather than baseline patient
characteristics. Higher ratios were not associated with improved outcomes.  (Anesth Analg
XXX;XXX:00–00)

KEY POINTS
• Question: In patients with acute intraoperative hemorrhage requiring administration of 3 or
more units of allogeneic red blood cells (RBCs) within 1 hour, are the ratios of transfused
component therapies associated with clinical outcomes?
• Findings: Transfusion ratios of plasma and platelets to RBCs were largely related to surgical
and laboratory hemostatic features rather than baseline patient characteristics, and higher
transfusion ratios were not associated with improved clinical outcomes.
• Meaning: Resuscitation strategies based on high ratios of plasma and platelets to RBCs may
not be broadly applicable to all patients with acute intraoperative hemorrhage.

GLOSSARY
ASA = American Society of Anesthesiologists; CAT = critical administration threshold; CI = confi-
dence interval; ICU = intensive care unit; INR = international normalized ratio; IQR = interquartile
range; IRB = institutional review board; LMW = low-molecular-weight; MBT = massive blood transfu-
sion; PCCs = prothrombin complex concentrates; RBCs = red blood cells; STROBE = Strengthening
the Reporting of Observational Studies in Epidemiology

From the *Department of Anesthesiology and Perioperative Medicine,
†Division of Biomedical Statistics and Informatics, and ‡Division of
Pulmonary and Critical Care Medicine, Mayo Clinic, Rochester, Minnesota.
Accepted for publication November 26, 2019.
Funding: This study was made possible by funding from the Mayo Clinic
Department of Anesthesiology and Perioperative Medicine and the Critical
Care Integrated Multidisciplinary Practice, Rochester, MN. In addition, this
study was supported by an NIH R01 grant (HL121232) to D.J.K. and by CTSA
Grant Number KL2 TR002379 to Dr Warner from the National Center for
Copyright © 2019 International Anesthesia Research Society
DOI: 10.1213/ANE.0000000000004609
Advancing Translational Science (NCATS). Its contents are solely the respon-
sibility of the authors and do not necessarily represent the official views of
the NIH.
The authors declare no conflicts of interest.
Supplemental digital content is available for this article. Direct URL citations
appear in the printed text and are provided in the HTML and PDF versions of
this article on the journal’s website (www.anesthesia-analgesia.org).
Reprints will not be available from the authors.
Address correspondence to Matthew A. Warner, MD, Department of Anesthe-
siology and Perioperative Medicine, Mayo Clinic, 200 First St SW, Rochester,
MN 55905. Address e-mail to warner.matthew@mayo.edu.

XXX XXX • Volume XXX • Number XXX www.anesthesia-analgesia.org

1
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 Massive Transfusion Ratios and Clinical Outcomes
I
n patients with acute blood loss secondary to trau-
matic injury, rapid administration of allogeneic
blood products including plasma, platelets, and red
blood cells (RBCs) as part of a balanced resuscitation
strategy has generally been associated with improved
clinical outcomes.1–3 Consequently, most major medi-
cal institutions have developed and implemented
transfusion protocols designed to deliver these blood
products in relatively fixed and high ratios, with many
centers using a single “massive transfusion” protocol
for all patients with rapid acute blood loss based on a
resuscitation strategy of 1:1:1 (plasma to platelets to
RBCs).4,5 Compared with patients randomly assigned
to a 1:1:2 strategy, patients receiving 1:1:1 ratio-based
resuscitation seemed to have earlier hemostasis and
less death by exsanguination in the first 24 hours after
major trauma, although there were no significant dif-
ferences in the primary outcomes of 24-hour or 30-day
mortality.6
Despite the widespread adoption of ratio-based
resuscitation strategies for all patients with major
hemorrhage, the safety and efficacy of such strate-
gies for patients with rapid, nontraumatic blood
loss remain unclear. Although large-volume transfu-
sions usually occur in surgical patients, few studies
have directly assessed the clinical outcomes for these
patients on the basis of plasma-to-RBC or platelet-
to-RBC ratios.7–10 Furthermore, to our knowledge,
no study has directly assessed time variations for
transfusion ratios during resuscitation from nontrau-
matic injury. Notably, some plausible reasons exist for
why optimal transfusion approaches differ between
patients with traumatic and nontraumatic injuries,
including differences in age, baseline health, func-
tional capacity, laboratory profiles, and clinical con-
text. Importantly, adults with traumatic injuries are
typically young with few baseline medical comorbid
conditions.1–3,6 As such, a heterogeneous cohort of sur-
gical patients with a higher burden of comorbid dis-
ease may be less likely to tolerate or benefit from high
resuscitation ratios than a trauma population.
The goal of this study was to assess the relation-
ships between plasma-to-RBC and platelet-to-RBC
ratios and clinical outcomes for surgical patients.
We hypothesized that, after careful adjustment for
confounding variables, higher plasma-to-RBC and
platelet-to-RBC ratios would not be associated with
improvements in clinical outcomes.
METHODS
This single-institution, historical observational cohort
study was approved by the Mayo Clinic institutional
review board (IRB; Rochester, MN), and the require-
ment for written informed consent was waived by the
IRB for those who had previously provided authori-
zation for medical record use in observational studies.
2   
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The Strengthening the Reporting of Observational
Studies in Epidemiology (STROBE) guidelines were
used in the design, analysis, presentation, and inter-
pretation of study results.11
We included patients ≥18 years with acute intra-
operative hemorrhage between January 1, 2011 and
December 31, 2015, which was defined as a transfu-
sion episode meeting or exceeding the critical admin-
istration threshold (CAT, ie, transfusion of 3 or more
units of allogeneic RBCs within 1 hour).12 CAT was
developed to identify patients with rapid, acute blood
loss requiring large-volume transfusion. CAT has the
distinct advantage over more arbitrary definitions of
massive transfusion (eg, 10 or more units of RBCs over
24 hours) in that it greatly reduces the potential for
survivor bias, given that some patients die before they
are able to receive 10 or more units of RBCs. In addi-
tion, CAT positivity allows for earlier identification of
patients with critical transfusion requirements and is
highly predictive of mortality in trauma patients.12–14
Patients were excluded if they denied use of their
medical records for observational research, were pre-
viously included in the study (ie, only the first surgi-
cal encounter meeting CAT positivity was included
for any given patient), had CAT positivity preced-
ing hospital admission (eg, a CAT-positive event in
an outpatient procedure center followed by eventual
hospital admission), or had an American Society of
Anesthesiologists (ASA) physical status score of VI
(ie, brain death, awaiting organ harvest). All surgical
patients were included, including patients undergo-
ing trauma surgery; however, trauma resuscitations
occurring before surgical intervention were not within
the scope of this investigation.
CAT positivity at the study institution could occur
independently of activation of the formal massive
blood transfusion (MBT) protocol because all intraop-
erative transfusion orders are issued emergently from
the blood bank. Thus, blood units may be available at
the bedside at the same rate regardless of MBT or non-
MBT ordering, and it is common practice for anesthe-
siologists to order desired blood components outside
of MBT activation. Nevertheless, a formal MBT pro-
tocol was implemented at the study institution in
2006 that may be activated both inside and outside
the operative environment through direct commu-
nication with the blood bank by phone or in person.
During the study period, this protocol entailed the
emergent release of 6 units of RBCs, 6 units of plasma,
and 1 unit of apheresis platelets, which is approxi-
mately equivalent to a 6-pack of whole-blood–derived
pooled platelets. Some or all of these products would
then be administered at the discretion of the order-
ing team. This protocol was consistent throughout the
hospital, regardless of medical or surgical service line.
All transfusion decisions were made at the discretion
ANESTHESIA & ANALGESIA
 EE Original Clinical Research Report
of the ordering team as informed by the unique clini-
cal scenario, including hemodynamic stability, ongo-
ing blood loss, and laboratory abnormalities.
The study cohort was selected by identifying all
adult patients meeting intraoperative CAT positiv-
ity utilizing the Transfusion DataMart, an institu-
tional data warehouse that contains comprehensive
information about each unit of transfused allogeneic
blood, including the exact date, time, and location of
blood product order, issue, and transfusion; specific
blood product characteristics (type, volume, and pro-
cessing); features regarding the ordering provider;
and pretransfusion and posttransfusion laboratory
features (eg, hemoglobin, platelet count, international
normalized ratio [INR]). Perioperative characteris-
tics for the surgical cohort were obtained from the
Perioperative DataMart, another institutional data-
base that contains comprehensive information (eg,
demographic, surgical, anesthetic, laboratory, vital
signs, medication characteristics) regarding patient
care in any of the institution’s acute care environ-
ments (ie, preoperative holding area, operating
room or procedural suites, postanesthesia care unit,
intensive care unit [ICU], or progressive care units).
Additional demographic features not available in
the Perioperative DataMart were extracted from the
Advanced Cohort Explorer, an institutional resource
that provides a near real-time feed of the institution’s
electronic health records and that allows for struc-
tured and unstructured (eg, free text) search queries
of both outpatient and inpatient environments. Each
of these resources has been extensively validated with
continuous monitoring of data quality similar to that
of other institutional data sources.15,16
Baseline demographic and clinical characteristics
were extracted for all patients and included age, sex,
ASA physical status score, Charlson Comorbidity
Index score, medical history, pretransfusion laboratory
values (hemoglobin, platelet count, and INR), surgery
type, surgery length, surgical urgency (emergent ver-
sus elective), estimated blood loss, and perioperative
administration of antiplatelet, antithrombotic, anti-
fibrinolytic, and hemostatic therapies. Transfusions
were extracted for plasma, platelets, RBCs, cryopre-
cipitate, and cell-salvaged blood for intraoperative use
and for the complete hospitalization. Because transfu-
sion ratios change throughout resuscitation, plasma-
to-RBC and platelet-to-RBC ratios were calculated at 3,
12, and 24 hours after the start of a CAT-positive event.
Patients meeting both CAT positivity and traditionally
defined massive transfusion positivity (ie, 10 or more
units of RBCs within 24 hours) were also identified.
Statistical Analyses
Data were descriptively summarized using frequency
and percent for categorical variables and medians and
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interquartile range (IQR) for continuous variables.
Unadjusted between-group comparisons based on
plasma-to-RBC or platelet-to-RBC ratios were per-
formed using χ2 and Fisher exact tests for categorical
variables and Kruskal-Wallis tests for continuous vari-
ables. A formal power analysis was deferred because
the incidence (and outcomes) of massive transfusion
according to CAT positivity has not been defined out-
side of traumatic settings.
Missing data for multivariable regression model-
ing were handled using multiple imputation with 25
independent, imputed data sets. Missing variables
included estimated blood loss (19.4%), pretransfu-
sion INR (18.8%), surgery length (1.4%), pretrans-
fusion platelet count (1.2%), ASA physical status
score (0.9%), and pretransfusion hemoglobin (0.3%).
Missing data were assumed to be random, although
patients with missing data were younger (median,
61.3 vs 64.5 years), more likely to be women (46.5%
vs 39.6%), more likely to have undergone solid organ
transplant surgery (19.7% vs 4.5%), and less likely to
have received heparin (8.0% vs 15.4%), warfarin (8.2%
vs 22.1%), or aspirin (30.6% vs 46.9%) than patients
without missing data.
After examining the distribution of transfused
products (plasma, platelets, and RBCs) but before per-
forming any inferential statistical analyses, plasma-to-
RBC ratios were divided into 4 quartiles designed to
maximize group size and to encompass the most com-
monly utilized transfusion ratios in protocol-based
resuscitation of 1:1 and 1:2. These quartile ratios were
0 (no plasma), 0.1–0.4 (ratio <1:2), 0.5–0.9 (ratio >1:2
but <1:1), and 1.0+ (ratio ≥1:1). Platelet-to-RBC ratios
were similarly divided into 4 quartiles, which were
designed to maximize group size and to include the
commonly used ratio of 1:1. These ratios included 0
(no platelets), 0.1–0.9 (ratio <1:1), 1.0–2.0 (ratio >1:1
but ≤2:1), and 2.1+ (ratio >2:1).
The primary outcome of interest was all-cause hos-
pital mortality, with secondary outcomes of ICU-free
days and hospital-free days. Free days were calcu-
lated by taking 28 minus the ICU or hospital length
of stay in days, with patients dying before day 28 or
those with lengths of stay >28 days receiving a score
of 0. Free days were chosen as an outcome measure
over simple length-of-stay measurements, given that
free days appropriately adjust for death before hospi-
tal discharge as a negative outcome and also attenuate
the potential impact of outliers due to truncation at
day 28. In contrast to length-of-stay measurements, a
greater number of free days implies a superior out-
come. ICU-free days were only calculated for patients
with postoperative ICU admission.
The relationships between clinical outcomes and
plasma-to-RBC and platelet-to-RBC ratios at 3, 12, and
24 hours after the initiation of a CAT-positive episode
3
 Massive Transfusion Ratios and Clinical Outcomes
were analyzed using multivariable regression models
adjusted for potentially confounding variables, includ-
ing age, sex, Charlson Comorbidity Index score, ASA
physical status score, emergency surgery, surgery type,
surgery duration, estimated blood loss, pre-CAT–pos-
itive laboratory values (hemoglobin, platelet count,
INR), antiplatelet therapy (aspirin or clopidogrel within
7 days), anticoagulant therapy (low-molecular-weight
[LMW] heparin within 24 hours, factor Xa inhibitors
within 3 days, direct thrombin inhibitors within 5 days,
heparin infusion within 24 hours, warfarin within 5
days), hemostatic agent use (prothrombin complex con-
centrates [PCCs], vitamin K, and intravenous antifibrino-
lytic agents, including tranexamic acid or aminocaproic
acid), and intraoperative volumes of crystalloids, non-
blood colloids, cell-salvaged blood, plasma, platelets,
and allogeneic RBCs. Continuous variables were mod-
eled as continuous data, dichotomous as binary, and cat-
egorical (surgery type) as categorical variables. Patients
who died before 3, 12, and 24 hours were not included
in 3/12/24-hour models. For analyses of plasma-to-RBC
ratios, the platelet-to-RBC ratio at the appropriate time
interval was also included as an adjustment variable
and vice versa for analyses of platelet-to-RBC ratio. Of
note, a 3-factor PCC was used during the study period
(Bebulin; Shire Plc, Lexington, MA).
The primary outcome of mortality was modeled
using logistic regression. We summarized the concor-
dance statistic. The secondary outcomes of ICU- and
hospital-free days were modeled using linear regres-
sion. Regression assumptions were assessed by plot-
ting the residuals against predicted values, and there
was little evidence of violations. To determine if any
potential association was consistent across a priori
designated subsets, we performed an interaction
analysis on groups undergoing cardiac surgery, non-
cardiac surgery, liver transplant surgery, and trauma
surgery, and for those meeting massive transfusion by
the traditional definition of 10 or more units of RBCs
within 24 hours. Additional sensitivity analyses were
performed excluding patients who did not receive any
plasma or platelet component therapies in the first 24
hours. As a post hoc analysis, we assessed a plasma-to-
RBC by platelet-to-RBC interaction term on outcomes.
We also examined the possibility of a platelet-to-RBC
interaction with antiplatelet agent use (aspirin or clop-
idogrel) with outcomes as a post hoc analysis.
Statistical significance was determined using a
2-tailed Bonferroni-corrected P value <.0167 based on
outcome analysis at 3 different time points (α, .05/3
tests). All analyses were performed using SAS version
9.4 (SAS Institute Inc, Cary, NC).
RESULTS
A total of 2385 patients met the criteria for CAT posi-
tivity and were included in the study (Supplemental
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Digital Content, Figure 1, http://links.lww.com/
AA/C988). The basic demographic and clinical
characteristics for the study cohort were stratified
by plasma-to-RBC (Table  1) and platelet-to-RBC
(Table  2) ratios. Most patients were men (57.7%),
with median (IQR) ASA physical status scores of III
(III–IV). Approximately 33.1% of patients underwent
cardiac surgery, followed by general surgery (14.1%),
solid organ transplantation (10.5%), and vascular
surgery (7.9%). Most patients had large-volume
intraoperative blood loss, as evidenced by median
(IQR) RBC volumes of 5 (4–9) units and estimated
blood loss of 1.9 (1.0–3.3) L. Those receiving any
plasma or platelets received higher total intraopera-
tive fluid volumes and had greater estimated blood
loss than those not receiving any plasma or platelets,
but intraoperative RBC and crystalloid and colloid
volumes did not increase uniformly with higher
plasma-to-RBC or platelet-to-RBC ratios. The great-
est RBC volumes were for patients with plasma-to-
RBC ratios between 0.5 and 0.9 and platelet-to-RBC
ratios between 0.1 and 0.9. Men had higher trans-
fusion ratios of both plasma to RBCs and platelets
to RBCs than women. Patients undergoing cardiac,
transplant, and vascular surgery tended to have
higher plasma-to-RBC and platelet-to-RBC ratios,
while patients who underwent general, orthopedic,
and urologic surgery had lower ratios. Laboratory
abnormalities (ie, platelet count, INR) increased with
higher transfusion ratios. Antifibrinolytic therapy
was used in 34.6% of cases, and PCCs were admin-
istered in approximately 2.9% of cases. Patients with
higher plasma-to-RBC and platelet-to-RBC ratios
were more likely to receive these adjunct hemostatic
therapies. There were no significant differences
in transfusion ratios on the basis of patient age or
Charlson Comorbidity Index score.
Plasma-to-RBC Ratio and Clinical Outcomes
Many patients received RBCs without plasma ther-
apy (35.6%), with median (IQR) RBC totals of 4 (3–5)
units. Only 14.9% of patients had a plasma-to-RBC
ratio of 1.0+. Of those receiving plasma, the most
common plasma-to-RBC ratio interval was 0.5–0.9
(46.5%, 714/1536), followed by 0.1–0.4 (30.4%,
467/1536) and 1.0+ (23.1%, 355/1536). Unadjusted
mortality rates by plasma-to-RBC ratio are presented
in Figure 1. In multivariable analyses, hospital mor-
tality did not differ significantly by plasma-to-RBC
ratio at 3, 12, or 24 hours (Table  3). Concordance
statistics of multivariable plasma-to-RBC mod-
els for mortality at 3, 12, and 24 hours were 0.84,
0.83, and 0.83, respectively. Unadjusted outcomes
of hospital- and ICU-free days are displayed in
Figure  2 and Supplemental Digital Content, Figure
2, http://links.lww.com/AA/C988, respectively.
ANESTHESIA & ANALGESIA
 EE Original Clinical Research Report

Table 1.  Patient Demographic and Clinical Characteristics by Plasma-to-RBC Ratio at 24 h

Ratio
0 0.1–0.4 0.5–0.9 1.0+ Total
Characteristica n = 849 n = 467 n = 714 n = 355 N = 2385
Baseline features
  Age, y 64.0 (52.9–73.8) 62.8 (52.5–73.3) 62.0 (50.9–71.7) 63.0 (52.6–72.4) 62.9 (52.3–72.7)
  Male sex 445 (52.4) 279 (59.7) 422 (59.1) 231 (65.1) 1377 (57.7)
  Charlson score, total 5 (3–8) 6 (4–8) 5 (3–8) 5 (3–8) 5 (3–8)
Surgery features
  ASA physical status score III (II–III) III (III–IV) III (III–IV) IV (III–IV) III (III–IV)
  Emergency surgery 117 (13.8) 95 (20.3) 207 (29.0) 119 (33.5) 538 (22.6)
  Surgery typeb
  Cardiac 164 (19.5) 125 (27.6) 310 (44.5) 177 (50.1) 776 (33.1)
  General 155 (18.5) 69 (15.2) 87 (12.5) 20 (5.7) 331 (14.1)
  Head/neck 9 (1.1) 1 (0.2) 1 (0.1) 1 (0.3) 12 (0.5)
  Neurology 25 (3.0) 12 (2.6) 10 (1.4) 2 (0.6) 49 (2.1)
  Ob/gyn 43 (5.1) 24 (5.3) 17 (2.4) 3 (0.8) 87 (3.7)
  Orthopedics 75 (8.9) 21 (4.6) 7 (1.0) 3 (0.8) 106 (4.5)
  Other 74 (8.8) 22 (4.9) 29 (4.2) 11 (3.1) 136 (5.8)
  Spine 32 (3.8) 19 (4.2) 10 (1.4) 0 (0) 61 (2.6)
  Thoracic 29 (3.5) 12 (2.6) 14 (2.0) 4 (1.1) 59 (2.5)
  Transplant 22 (2.6) 33 (7.3) 118 (16.9) 73 (20.7) 246 (10.5)
  Trauma 47 (5.6) 23 (5.1) 27 (3.9) 15 (4.2) 112 (4.8)
  Urology 107 (12.7) 53 (11.7) 19 (2.7) 4 (1.1) 183 (7.8)
  Vascular 58 (6.9) 39 (8.6) 48 (6.9) 40 (11.3) 185 (7.9)
  Surgery length, min 277 (179–397) 335 (243–489) 346 (226–468) 371 (253–502) 324 (216–456)
  Estimated blood loss, L 1.5 (0.9–2.3) 2.5 (1.4–4.0) 2.2 (1.2–4.1) 2.5 (1.3–4.5) 1.9 (1.0–3.3)
  Platelet-to-RBC ratio
  0 720 (84.8) 140 (30.0) 134 (18.8) 62 (17.5) 1056 (44.3)
  0.1–0.9 9 (1.1) 100 (21.4) 74 (10.4) 10 (2.8) 193 (8.1)
  1.0–2.0 92 (10.8) 181 (38.8) 304 (42.6) 112 (31.5) 689 (28.9)
  2.1+ 28 (3.3) 46 (9.9) 202 (28.3) 171 (48.2) 447 (18.7)
  RBC units 4 (3, 5) 7 (5, 11) 8 (5, 13) 6 (4, 10) 5 (4, 9)
  Crystalloid volume, L 4.1 (2.5–6.2) 5.2 (2.9–7.9) 4.1 (2.7–6.3) 3.9 (2.6–5.8) 4.2 (2.6–6.5)
  Colloid volume, L 1.0 (0.5–1.5) 1.1 (0.5–2.0) 1.0 (0.1–1.6) 0.6 (0.01–1.5) 1.0 (0.1–1.8)
  Intraoperative volume, total, L 7.4 (4.9–9.2) 11.3 (7.9–15.5) 11.9 (8.4–16.4) 12.8 (9.2–16.9) 10.0 (6.8–14.3)
Laboratory values before CAT+
  Hemoglobin, g/dL 8.3 (7.4–9.2) 8.3 (7.4–9.5) 8.2 (7.4–9.3) 8.3 (7.6–9.2) 8.3 (7.4–9.3)
  Platelet count, ×10 9/L 223 (149–306) 185 (113–256) 151 (92–215) 130 (80–190) 178 (109–256)
 INR 1.1 (1.0–1.3) 1.2 (1.1–1.5) 1.3 (1.1–1.8) 1.5 (1.2–2.1) 1.3 (1.1–1.6)
Medications before CAT+
  Heparin infusion 66 (7.8) 60 (12.8) 117 (16.4) 56 (15.8) 299 (12.5)
  Direct thrombin inhibitor 2 (0.2) 2 (0.4) 3 (0.4) 7 (2.0) 14 (0.6)
 Warfarin 96 (11.3) 59 (12.6) 138 (19.3) 107 (30.1) 400 (16.8)
 Aspirin 328 (38.6) 190 (40.7) 301 (42.2) 151 (42.5) 970 (40.7)
  LMW heparin 49 (5.8) 31 (6.6) 23 (3.2) 12 (3.4) 115 (4.8)
 Clopidogrel 43 (5.1) 29 (6.2) 70 (9.8) 23 (6.5) 165 (6.9)
  Factor Xa inhibitor 6 (0.7) 3 (0.6) 7 (1.0) 2 (0.6) 18 (0.8)
Hemostatic medications
  Vitamin K 9 (1.1) 17 (3.6) 30 (4.2) 15 (4.2) 71 (3.0)
  Antifibrinolytic agents 181 (21.3) 148 (31.7) 321 (45.0) 175 (49.3) 825 (34.6)
 PCCs 5 (0.6) 11 (2.4) 27 (3.8) 26 (7.3) 69 (2.9)
Abbreviations: ASA, American Society of Anesthesiologists; CAT+, critical administration threshold positive; INR, international normalized ratio; LMW, low-
molecular-weight; Ob/gyn, obstetrics/gynecology; PCCs, prothrombin complex concentrates; RBC, red blood cell.
a
Categorical variables are displayed as n (%) and continuous variables as median (interquartile range).
b
Procedure type missing for 42 patients, including 9 in the 0 category, 14 in the 0.1–0.4 category, 17 in the 0.5–0.9 category, and 2 in the 1.0+ category.

In multivariable analyses, ratios at 12 and 24 hours
were associated with a reduced number of hospital-
free days (when compared to a reference ratio of 0;
overall P = .002), with the greatest mean (95% confi-
dence interval [CI]) decrease of 1.92 (0.89–2.95) days
observed for those with plasma-to-RBC ratios of 0.5–
0.9 at 12 hours (Table  4). There were no significant
associations between ICU-free days and plasma-to-
RBC ratio.
Platelet-to-RBC Ratio and Clinical Outcomes
Many patients received RBCs without platelets (44.3%).
Nearly half of patients (47.6%) had a platelet-to-RBC
ratio ≥1.0. Of those receiving platelets, the most com-
mon platelet-to-RBC ratio interval was 1.0–2.0 (51.8%,
689/1329), followed by 2.1+ (33.6%, 447/1329) and
0.1–0.9 (14.5%, 193/1329). In multivariable analyses,
the odds for mortality were increased for those receiv-
ing platelets by 12 and 24 hours, with the greatest odds

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 Massive Transfusion Ratios and Clinical Outcomes

Table 2.  Patient Demographic and Clinical Characteristics by Platelet-to-RBC Ratio at 24 h

Ratio
0 0.1–0.9 1.0–2.0 2.1+ Total
Characteristica n = 1056 n = 193 n = 689 n = 447 N = 2385
Baseline features
 Age 62.4 (51.4–71.7) 58.2 (46.3–70.3) 64.4 (53.6–73.8) 64.5 (55.7–73.3) 62.9 (52.3–72.7)
  Male sex 570 (54.0) 126 (65.3) 411 (59.7) 270 (60.4) 1377 (57.7)
  Charlson score, total 5 (3–8) 5 (3–8) 6 (4–8) 6 (4–8) 5 (3–8)
Surgery features
  ASA physical status score III (III–III) III (III–IV) III (III–IV) IV (III–IV) III (III–IV)
  Emergency surgery 198 (18.8) 44 (22.8) 180 (26.1) 116 (26.0) 538 (22.6)
  Procedure typeb
  Cardiac 189 (18.2) 33 (17.8) 307 (45.3) 247 (55.9) 776 (33.1)
  General 203 (19.5) 35 (18.9) 81 (12.0) 12 (2.7) 331 (14.1)
  Head/neck 9 (0.9) 1 (0.5) 2 (0.3) 0 (0) 12 (0.5)
  Neurology 31 (3.0) 4 (2.2) 8 (1.2) 6 (1.4) 49 (2.1)
  Ob/gyn 64 (6.2) 8 (4.3) 12 (1.8) 3 (0.7) 87 (3.7)
  Orthopedics 78 (7.5) 14 (7.6) 11 (1.6) 3 (0.7) 106 (4.5)
  Other 86 (8.3) 9 (4.9) 27 (4.0) 14 (3.2) 136 (5.8)
  Spine 33 (3.2) 3 (1.6) 18 (2.7) 7 (1.6) 61 (2.6)
  Thoracic 31 (3.0) 7 (3.8) 19 (2.8) 2 (0.5) 59 (2.5)
  Transplant 44 (4.2) 17 (9.2) 94 (13.9) 91 (20.6) 246 (10.5)
  Trauma 68 (6.5) 11 (5.9) 29 (4.3) 4 (0.9) 112 (4.8)
  Urology 126 (12.1) 30 (16.2) 25 (3.7) 2 (0.5) 183 (7.8)
  Vascular 77 (7.4) 13 (7.0) 44 (6.5) 51 (11.5) 185 (7.9)
  Surgery length, min 275 (173–391) 367 (244–556) 343 (232–476) 394 (264–502) 324 (216–456)
  Estimated blood loss, L 1.6 (0.9–2.5) 3.5 (2.0–5.4) 2.0 (1.1–4.0) 2.4 (1.3–4.3) 1.9 (1.0–3.3)
  Plasma-to-RBC ratio
  0 720 (68.2) 9 (4.7) 92 (13.4) 28 (6.3) 849 (35.6)
  0.1–0.4 140 (13.3) 100 (51.8) 181 (26.3) 46 (10.3) 467 (19.6)
  0.5–0.9 134 (12.7) 74 (38.3) 304 (44.1) 202 (45.2) 714 (29.9)
  1.0+ 62 (5.9) 10 (5.2) 112 (16.3) 171 (38.3) 355 (14.9)
  RBC units 4 (3–5) 10 (8–14) 6 (5–12) 7 (5–11) 5 (4–9)
  Crystalloid volume, L 4.3 (2.6–6.3) 6.0 (3.5–9.2) 4.0 (2.6–6.4) 3.8 (2.6–5.8) 4.2 (2.6–6.5)
  Colloid volume, L 1.0 (0.5–1.8) 1.3 (0.5–2.5) 0.9 (0.1–1.6) 0.6 (0.1–1.5) 1.0 (0.1–1.8)
  Intraoperative volume, total, L 7.7 (5.1–10.5) 13.7 (9.7–18.7) 11.5 (8.0–16.0) 13.1 (9.7–17.6) 10.0 (6.8–14.3)
Laboratory values before CAT+
  Hemoglobin, g/dL 8.3 (7.4–9.3) 8.6 (7.7–9.8) 8.2 (7.3–9.2) 8.2 (7.5–9.1) 8.3 (7.4–9.3)
  Platelet count, ×10 9/L 231 (161–313) 207 (133–296) 145 (93–205) 105 (69–168) 178 (109–256)
 INR 1.2 (1.0–1.4) 1.2 (1.1–1.5) 1.3 (1.1–1.7) 1.4 (1.1–1.8) 1.3 (1.1–1.6)
Medications before CAT+
  Heparin infusion 74 (7.0) 12 (6.2) 117 (17.0) 96 (21.5) 299 (12.5)
  Direct thrombin inhibitor 4 (0.4) 0 (0) 4 (0.6) 6 (1.3) 14 (0.6)
 Warfarin 137 (13.0) 21 (10.9) 123 (17.9) 119 (26.6) 400 (16.8)
 Aspirin 379 (35.9) 72 (37.3) 314 (45.6) 205 (45.9) 970 (40.7)
  LMW heparin 65 (6.2) 13 (6.7) 23 (3.3) 14 (3.1) 115 (4.8)
 Clopidogrel 53 (5.0) 6 (3.1) 60 (8.7) 46 (10.3) 165 (6.9)
  Factor Xa inhibitor 9 (0.9) 1 (0.5) 6 (0.9) 2 (0.4) 18 (0.8)
Hemostatic medications
  Vitamin K 28 (2.7) 9 (4.7) 23 (3.3) 11 (2.5) 71 (3.0)
  Antifibrinolytic agents 202 (19.1) 46 (23.8) 316 (45.9) 261 (58.4) 825 (34.6)
 PCCs 2 (0.2) 8 (4.1) 27 (3.9) 32 (7.2) 69 (2.9)
Abbreviations: ASA, American Society of Anesthesiologists; CAT+, critical administration threshold positive; Ob/gyn, obstetrics/gynecology; INR, international
normalized ratio; LMW, low-molecular-weight; PCCs, prothrombin complex concentrates; RBC, red blood cell.
a
Categorical variables are displayed as n (%) and continuous variables as median (interquartile range).
b
Procedure type missing for 42 patients, including 17 in the 0 category, 8 in the 0.1–0.9 category, 12 in the 1.0–2.0 category, and 5 in the 2.1+ category.

observed in those with a ratio of 0.1–0.9 at 24 hours (odds
ratio, 3.34 [95% CI, 1.62–6.88]; Table 3). Concordance sta-
tistics at 3, 12, and 24 hours were 0.84, 0.84, and 0.83,
respectively. Platelet-to-RBC ratios were not associated
with hospital- or ICU-free days after multiple compari-
sons adjustment.
Sensitivity Interaction Analyses
In testing for interactions for all 3 outcomes at all
3 time points, there was no significant interaction
between either plasma-to-RBC or platelet-to-RBC
ratio and cardiac surgery, noncardiac surgery, liver
transplant surgery, massive transfusion, or trauma
surgery for the outcomes of in-hospital mortality and
hospital-free days. However, for the outcome of ICU-
free days, there was a significant interaction (P = .003)
between trauma and plasma-to-RBC ratio at 24 hours,
such that patients with both trauma and a plasma-to-
RBC ratio >1.0 had additional reductions in ICU-free

6   
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 EE Original Clinical Research Report
days (Supplemental Digital Content, Table 1, http://
links.lww.com/AA/C988). When patients who
received no plasma or platelets were excluded, there
were no significant associations between plasma-to-
RBC or platelet-to-RBC ratio and the outcomes of hos-
pital-free days, ICU-free days, or hospital mortality
(Supplemental Digital Content, Table 2, http://links.
lww.com/AA/C988). A cross-tabulation of plasma-
to-RBC and platelet-to-RBC ratios is provided in
Supplemental Digital Content, Table 3, http://links.
lww.com/AA/C988. There was no significant evi-
dence of an interaction between plasma-to-RBC and
platelet-to-RBC ratios with outcomes. Similarly, there
was no interaction between antiplatelet therapy use
and platelet-to-RBC ratio with outcomes.
DISCUSSION
In this study of plasma-to-RBC and platelet-to-RBC
ratios in a diverse cohort of surgical patients with clin-
ically significant intraoperative hemorrhage, higher
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Figure 1. Mortality by plasma-to-RBC and plate-
let-to-RBC ratio. P values calculated from the χ2
test. RBC indicates red blood cells.
blood product ratios were observed for men, emer-
gency surgery, and cardiac, transplant, and vascu-
lar surgery. Antifibrinolytic therapy use increased in
accordance with plasma- and platelet-to-RBC ratios.
There were no clear relationships between transfusion
ratios and patient age or baseline severity of illness,
although patients with higher transfusion ratios had
more deranged hemostatic laboratory values. Higher
ratios were not associated with improved clinical
outcomes, even after careful adjustment for severity
of illness and important clinical and demographic
features.
To our knowledge, this study provides the most
comprehensive assessment to date of transfusion ratios
outside of trauma settings. Findings consistent with
ours have been reported in several recent observa-
tional studies. In a study of approximately 600 surgical
and critically ill patients receiving massive transfusion
for nontraumatic indications, higher plasma-to-RBC
and platelet-to-RBC ratios were not associated with
7
 Massive Transfusion Ratios and Clinical Outcomes

Table 3.  Associations Between Plasma-to-RBC Ratio, Platelet-to-RBC Ratio, and Hospital Mortality Using
Multivariable Logistic Regressiona
3h 12 h 24 h
Ratio No. Death (%) Odds Ratio (95% CI) Pb No. Death (%) Odds Ratio (95% CI) Pb No. Death (%) Odds Ratio (95% CI) Pb
Plasma:RBC .33 .14 .35
 0 1135 70 (6.2) 1.00 (ref) 855 33 (3.9) 1.00 (ref) 837 31 (3.7) 1.00 (ref)
 0.1–0.4 318 42 (13.2) 1.55 (0.95–2.55) .08 422 31 (7.3) 1.06 (0.58–1.92) .85 449 33 (7.3) 1.03 (0.56–1.87) .93
 0.5–0.9 554 64 (11.6) 1.10 (0.69–1.76) .68 676 90 (13.3) 1.70 (0.99–2.92) .05 695 83 (11.9) 1.48 (0.85–2.59) .17
 1.0+ 359 51 (14.2) 1.25 (0.71–2.22) .44 390 50 (12.8) 1.44 (0.75–2.76) .27 351 46 (13.1) 1.52 (0.78–2.94) .22
Platelet:RBC .61 .009 .004
 0 1350 87 (6.4) 1.00 (ref) 1069 39 (3.6) 1.00 (ref) 1032 32 (3.1) 1.00 (ref)
 0.1–0.9 133 22 (16.5) 1.49 (0.73–3.04) .27 174 24 (13.8) 3.07 (1.56–6.08) .001 181 21 (11.6) 3.34 (1.62–6.88) .001
 1.0–2.0 570 73 (12.8) 1.28 (0.83–1.97) .27 676 81 (12.0) 1.99 (1.19–3.33) .008 675 80 (11.9) 2.33 (1.35–4.00) .002
 2.1+ 313 45 (14.4) 1.26 (0.71–2.24) .44 424 60 (14.2) 1.85 (0.99–3.47) .06 444 60 (13.5) 2.18 (1.14–4.17) .02
Abbreviations: CI, confidence interval; RBC, red blood cell.
a
The model included age, sex, Charlson Comorbidity Index score, American Society of Anesthesiologists physical status score, emergency surgery, surgery type,
surgery duration, estimated blood loss, laboratory values before critical administration threshold positive (hemoglobin, platelet count, international normalized
ratio), antiplatelet therapy (aspirin, clopidogrel), anticoagulants (low-molecular-weight heparin, factor Xa inhibitors, direct thrombin inhibitors, heparin infusion,
warfarin), hemostatic agents (prothrombin complex concentrates, vitamin K, antifibrinolytics), platelet-to-RBC ratio (for plasma:RBC analyses), plasma-to-RBC ratio
(for platelet:RBC analyses), and intraoperative volumes of crystalloids, colloids, cell-salvaged blood, plasma, platelets, and RBCs.
b
The first P value represents the overall relationship, with subsequent P values representing individual comparisons with the reference group (ie, plasma:RBC or
platelet:RBC ratio of 0).

Figure 2. Box plot of hospital-free days by

plasma-to-RBC and platelet-to-RBC ratio. P
values calculated from the Kruskal-Wallis
test. IQR indicates interquartile range;
RBC, red blood cells.

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 EE Original Clinical Research Report

Table 4.  Associations Between Plasma-to-RBC Ratio, Platelet-to-RBC Ratio, and Hospital- and ICU-Free Days
Within 28 d Using Multivariable Linear Regressiona
3h 12 h 24 h
Median Mean Estimate Median Mean Estimate Mean Estimate
Outcome No. (IQR) (95% CI) Pb No. (IQR) (95% CI) Pb No. Median (IQR) (95% CI) Pb
Hospital-free
days
 Plasma:RBC .17 .002 .002
  0 1135 20 (12–23) 0 (ref) 855 21 (15–23) 0 (ref) 837 21 (16–23) 0 (ref)
  0.1–0.4 318 17 (3–21) −1 (−2 to −0.1) .03 422 18 (6–21) −2 (−3 to −0.4) .006 449 17 (6–21) −2 (−3 to −1) .002
  0.5–0.9 554 16 (1–21) −0.6 (−2 to 0.4) .22 676 15 (0–20) −2 (−3 to −0.9) <.001 695 15 (0–20) −2 (−3 to −1) <.001
  1.0+ 359 14 (0–19) −0.7 (−2 to 0.6) .28 390 15 (0–19) −1 (−3 to 0.2) .09 351 15 (0–20) −1.3 (−2.6 to 0.1) .06
 Platelet:RBC .22 .04 .03
  0 1350 20 (12–23) 0 (ref) 1069 21 (14–23) 0 (ref) 1032 21 (15–23) 0 (ref)
  0.1–0.9 133 17 (0.4–21) 0.4 (−1 to 2) .62 174 16 (0.3–21) −1 (−2 to 0.5) .18 181 17 (5–21) −1 (−3 to 0.3) .13
  1.0–2.0 570 16 (2–21) −0.5 (−1 to 0.5) .35 676 16 (1–20) −1 (−2 to −0.4) .005 675 16 (0.1–20) −1 (−2 to −0.4) .007
  2.1+ 313 13 (0–19) −1.3 (−3 to 0) .06 424 14 (0–19) −2 (−3 to −0.1) .03 444 14 (0–19) −2 (−3 to −0.5) .007
ICU-free days
 Plasma:RBC .63 .36 .35
  0 355 25 (19–27) 0 (ref) 241 25 (21–27) 0 (ref) 234 25.5 (21.9–26.9) 0 (ref)
  0.1–0.4 133 25 (14–26) −1 (−4 to 0.8) .20 174 25 (19–27) −0.3 (−2 to 2) .75 188 24.9 (19.3–26.5) −0.4 (−2 to 2) .73
  0.5–0.9 314 23 (15–26) −0.7 (−3 to 1) .43 374 23 (15–26) −2 (−3 to 0.4) .11 385 23.9 (15.3–26.0) −1 (−3 to 0.5) .16
  1.0+ 250 24 (16–26) −0.8 (−3 to 1) .49 252 24 (16–26) −2 (−4 to 0.7) .17 226 23.8 (15.4–26.2) −2 (−4 to 0.4) .11
 Platelet:RBC .90 .13 .14
  0 454 25 (19–27) 0 (ref) 329 25 (21–27) 0 (ref) 311 25 (21−27) 0 (ref)
  0.1–0.9 46 23 (0–26) −1 (−5 to 2) .50 66 23 (0–26) −3 (−6 to −0.4) .02 69 23 (11–26) −3 (−6 to −0.3) .03
  1.0–2.0 348 24 (17–26) −0.4 (−2 to 1) .62 38 24 (16–26) −2 (−3 to 0.3) .10 376 24 (16–26) −1 (−3 to 0.4) .12
  2.1+ 204 24 (16–26) −0.2 (−3 to 2) .84 266 24 (15–26) −1 (−4 to 1) .25 277 24 (16–26) −1 (−3 to 1) .40
Abbreviations: CI, confidence interval; ICU, intensive care unit; IQR, interquartile range; RBC, red blood cell.
a
The model included age, sex, Charlson comorbidity index score, American Society of Anesthesiologists physical status score, emergency surgery, surgery type,
surgery duration, estimated blood loss, laboratory values before critical administration threshold positive (hemoglobin, platelet count, international normalized
ratio), antiplatelet therapy (aspirin, clopidogrel), anticoagulants (low-molecular-weight heparin, factor Xa inhibitors, direct thrombin inhibitors, heparin infusion,
warfarin), hemostatic agents (prothrombin complex concentrates, vitamin K, antifibrinolytics), platelet-to-RBC ratio (for plasma:RBC analyses), plasma-to-RBC ratio
(for platelet:RBC analyses), and intraoperative volumes of crystalloids, colloids, cell-salvaged blood, plasma, platelets, and RBCs.
b
The first P value represents the overall relationship, with subsequent P values representing individual comparisons with the reference group (ie, plasma:RBC or
platelet:RBC ratio of 0).

improvements in 30-day mortality.7 Similarly, a study
of 865 massive transfusion events, of which nearly
90% were nontraumatic, did not show any difference
in patient mortality based on plasma-to-RBC ratio.8
Hence, the broad application of high fixed-ratio trans-
fusion strategies, based on clinical data derived from
trauma patients, may not be uniformly applicable to
all patients with rapid intraoperative bleeding.
Approximately one-third of our study cohort
underwent cardiac surgery with no significant interac-
tion between transfusion ratios and outcomes. This is
in contrast to recent findings by Delaney et al,17 who
noted lower mortality and improvement in organ dys-
function scores with higher ratios. Besides utilizing dif-
ferent definitions for study inclusion (CAT positivity
in our study versus transfusion totals of at least 6 units
of RBCs or 8 units of all blood components), Delaney
et al17 analyzed high versus low ratios by dichotomiz-
ing patients above or below 1.0:1.0 (plasma to RBCs)
and 0.2:1.0 (apheresis platelets to RBCs). In our study,
ratio data were divided into 4 unique quartiles rather
than dichotomized, with a sensitivity analysis exclud-
ing patients not receiving any component therapies.
Furthermore, we adjusted for a wider array of baseline
characteristics and intraoperative variables but did
not adjust for aortic cross-clamp or cardiopulmonary
bypass time. Future investigations are warranted to
define optimal transfusion ratios in cardiac surgery.
Apart from clinical outcomes, there are potential
financial ramifications related to the use of lower
transfusion-ratio strategies. First, activity-based costs
of plasma transfusion have been estimated at approxi-
mately $410 per unit.18 Activity-based analyses pro-
vide a more accurate representation of the cost of a
transfusion episode because they account for both
direct (eg, product acquisition, laboratory testing, stor-
age, administration) and indirect costs (eg, discarded
products, treatment of transfusion-related complica-
tions). Although activity-based costs for platelets have
not been published, activity-based costs are typically
3–5 times higher than acquisition costs.19 Acquisition
costs for an apheresis platelet unit are approximately
$500; therefore, the total activity-based costs for plate-
lets could be conservatively estimated at $1500 per
unit. Hence, exclusion of extraneous plasma and plate-
let units from critical transfusion events could result in
substantial institutional cost savings.
Limitations
The current study has several limitations. First, the
data are retrospective and, thus, have the potential
for residual confounding. Although we were able to

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 Massive Transfusion Ratios and Clinical Outcomes
capture and adjust for a multitude of important peri-
operative factors selected a priori, it is nonetheless
possible that outcomes for those with higher transfu-
sion ratios were simply a reflection of either greater
surgical insults or sicker patients. In addition, we were
unable to distinguish blood products that arrived to
the operating room secondary to MBT activation or
by emergent release from the blood bank, and poten-
tial differences in severity of bleeding may exist
between these 2 scenarios; however, given that CAT
positivity requires at least 3 units of RBCs transfused
within 1 hour, it is certain that all patients had rapid
intraoperative bleeding regardless of the manner of
blood delivery. Similarly, microvascular bleeding and
coagulopathy may occur in the absence of substantial
derangements in laboratory hemostatic tests. Notably,
we did not assess the potential impact of resuscitation
strategies on changes in platelet function, fibrinogen
concentrations, or the development of dilutional ane-
mia. Furthermore, analyses were compared between
each transfusion-ratio group and a reference group
having a platelet or plasma-to-RBC ratio of 0, which
may have increased the probability for unmeasured
confounding and the subsequent magnification of
observed-effect sizes despite deliberate multivari-
able adjustment. To account for this, we performed a
sensitivity analysis with explicit exclusion of patients
receiving only RBCs. The results showed no signifi-
cant differences in free days or mortality between
groups based on higher and lower transfusion ratios.
This provides further evidence against superiority
of outcomes with the use of higher-ratio resuscita-
tion strategies for patients with critical intraoperative
hemorrhage.
A second limitation was the heterogeneous nature
of the study cohort. Although this was an intentional
part of the study design, it resulted in subgroup
analyses that were underpowered for the outcome of
mortality. Moreover, although it is quite plausible that
optimal transfusion ratios may indeed differ based on
the surgical cohort, additional studies are clearly war-
ranted to study transfusion ratios in unique surgical
populations.
Third, there are likely many clinically relevant
outcome measures for transfusion strategies that
were not explored in this investigation (eg, myo-
cardial or cerebral ischemic events, acute kidney
injury, transfusion-related respiratory complications,
changes in lactate clearance, improvements in micro-
circulatory oxygen delivery, cessation of microvas-
cular bleeding). It is possible that small alterations
in transfusion ratios could result in more meaning-
ful alterations in these outcome measures. Notably,
two-thirds of transfusion-related mortality is attrib-
utable to transfusion-related respiratory complica-
tions, such as transfusion-related acute lung injury
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and transfusion-associated circulatory overload, or
transfusion-associated infection.20 Future prospective
studies must be designed to look beyond simplified
outcome measures such as mortality and lengths of
stay, which are likely to provide an incomplete assess-
ment of the downstream consequences of transfusion.
CONCLUSIONS
There was no evidence for improved clinical outcomes
in a diverse cohort of surgical patients treated with
increasing plasma-to-RBC and platelet-to-RBC ratios.
Transfusion strategies seemed to be largely tailored on
the basis of procedural and hemostatic characteristics
(ie, surgery type, pretransfusion laboratory features)
rather than baseline patient features (ie, age, sever-
ity of illness). High ratios were not associated with
improved outcomes and may not be directly applica-
ble to all patients with rapid intraoperative bleeding.
Future studies should evaluate optimal resuscitation
strategies according to unique patient demographic
and clinical characteristics, utilizing novel end points
for the assessment of resuscitation adequacy. E
DISCLOSURES
Name: Matthew A. Warner, MD.
Contribution: This author helped in concept and design, data
acquisition, interpretation of data, critical writing, revision of
intellectual content, and final approval of the manuscript.
Name: Ryan D. Frank, MS.
Contribution: This author helped in concept and design, anal-
ysis and interpretation of data, critical revision of intellectual
content, and final approval of the manuscript.
Name: Timothy J. Weister, MSN, RN.
Contribution: This author helped in data acquisition, criti-
cal revision of intellectual content, and final approval of the
manuscript.
Name: Nageswar R. Madde, MS.
Contribution: This author helped in data acquisition, criti-
cal revision of intellectual content, and final approval of the
manuscript.
Name: Ognjen Gajic, MD.
Contribution: This author helped in concept and design, inter-
pretation of data, critical revision of intellectual content, and
final approval of the manuscript.
Name: Daryl J. Kor, MD.
Contribution: This author helped in concept and design, inter-
pretation of data, critical revision of intellectual content, and
final approval of the manuscript.
This manuscript was handled by: Susan Goobie, MD, FRCPC.
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