text:
Increased plasma and platelet to red blood cell ratios improves outcome in 466 massively transfused civilian trauma patients.
ABSTRACT To determine the effect of blood component ratios in massive transfusion (MT), we hypothesized that increased use of plasma and platelet to red blood cell (RBC) ratios would result in decreased early hemorrhagic death and this benefit would be sustained over the ensuing hospitalization.
Civilian guidelines for massive transfusion (MT > or =10 units of RBC in 24 hours) have typically recommend a 1:3 ratio of plasma:RBC, whereas optimal platelet:RBC ratios are unknown. Conversely, military data shows that a plasma:RBC ratio approaching 1:1 improves long term outcomes in MT combat casualties. There is little consensus on optimal platelet transfusions in either civilian or military practice. At present, the optimal combinations of plasma, platelet, and RBCs for MT in civilian patients is unclear.
Records of 467 MT trauma patients transported from the scene to 16 level 1 trauma centers between July 2005 and June 2006 were reviewed. One patient who died within 30 minutes of admission was excluded. Based on high and low plasma and platelet to RBC ratios, 4 groups were analyzed.
Among 466 MT patients, survival varied by center from 41% to 74%. Mean injury severity score varied by center from 22 to 40; the average of the center means was 33. The plasma:RBC ratio ranged from 0 to 2.89 (mean +/- SD: 0.56 +/- 0.35) and the platelets:RBC ratio ranged from 0 to 2.5 (0.55 +/- 0.50). Plasma and platelet to RBC ratios and injury severity score were predictors of death at 6 hours, 24 hours, and 30 days in multivariate logistic models. Thirty-day survival was increased in patients with high plasma:RBC ratio (> or =1:2) relative to those with low plasma:RBC ratio (<1:2) (low: 40.4% vs. high: 59.6%, P < 0.01). Similarly, 30-day survival was increased in patients with high platelet:RBC ratio (> or =1:2) relative to those with low platelet:RBC ratio (<1:2) (low: 40.1% vs. high: 59.9%, P < 0.01). The combination of high plasma and high platelet to RBC ratios were associated with decreased truncal hemorrhage, increased 6-hour, 24-hour, and 30-day survival, and increased intensive care unit, ventilator, and hospital-free days (P < 0.05), with no change in multiple organ failure deaths. Statistical modeling indicated that a clinical guideline with mean plasma:RBC ratio equal to 1:1 would encompass 98% of patients within the optimal 1:2 ratio.
Current transfusion practices and survival rates of MT patients vary widely among trauma centers. Conventional MT guidelines may underestimate the optimal plasma and platelet to RBC ratios. Survival in civilian MT patients is associated with increased plasma and platelet ratios. Massive transfusion practice guidelines should aim for a 1:1:1 ratio of plasma:platelets:RBCs.
- [Show abstract] [Hide abstract]
ABSTRACT: Traumatic injury is the leading cause of death worldwide. The rapid evaluation and correction of injuries in these patients is paramount to preventing uncontrolled decompensation and death. Damage control strategies are a compendium of techniques refined over decades of surgical care that focus on the rapid correction of deranged physiology, control of contamination and blood loss, and resuscitation of critical patients. Damage control resuscitation (DCR) focuses on the replacement of lost blood volume in a manner mimicking whole blood, control of crystalloid administration, and permissive hypotension. Damage control laparotomy controls gastrointestinal contamination and bleeding in the operative suite, allowing rapid egress to the intensive care unit for ongoing resuscitation. Pelvic packing, an adjunct to DCR, provides a means to control hemorrhage from severe pelvic fractures. Temporary vascular shunts restore perfusion, while resuscitation and reconstruction are ongoing. Taken together, these strategies provide the trauma surgeon with a powerful arsenal to preserve life in the transition from injury to the shock trauma room to the intensive care unit.European Journal of Trauma and Emergency Surgery 04/2014; 40(2):143-150. · 0.38 Impact Factor - [Show abstract] [Hide abstract]
ABSTRACT: Planned re-laparotomy or damage control laparotomy (DCL), first described by Dr. Harlan Stone in 1983, has become a widely utilized technique in a broad range of patients and operative situations. Studies have validated the use of DCL by demonstrating decreased mortality and morbidity in trauma, general surgery and abdominal vascular catastrophes. Indications for planned re-laparotomy include severe physiologic derangements, coagulopathy, concern for bowel ischemia, and abdominal compartment syndrome. The immunology of DCL patients is not well described in humans, but promising animal studies suggest a benefit from the open abdomen (OA) and several human trials on this subject are currently underway. Optimal critical care of patients with OA's, including sedation, paralysis, nutrition, antimicrobial and fluid management strategies have been associated with improved closure rates and recovery.European Journal of Trauma and Emergency Surgery 04/2014; 40(2):135-142. · 0.38 Impact Factor - Michael W. Cripps, Matthew E. Kutcher, Aaron Daley, Ryan C. McCreery, Molly D. Greenberg, Leslie M. Cachola, Brittney J. Redick, Mary F. Nelson, Mitchell Jay Cohen[Show abstract] [Hide abstract]
ABSTRACT: BACKGROUND The purpose of this study was to characterize the cause of death in severely injured trauma patients to define potential responses to resuscitation. METHODS Prospective analysis of 190 critically injured patients who underwent massive transfusion protocol (MTP) activation or received massive transfusion (>10 U of packed red blood cells [RBC] per 24 hours). Cause of death was adjudicated into one of four categories as follows: (1) exsanguination, (2) early physiologic collapse, (3) late physiologic collapse, and (4) nonsurvivable injury. RESULTS A total 190 patients underwent massive transfusion or MTP with 76 deaths (40% mortality), of whom 72 deaths were adjudicated to one of four categories: 33.3% died of exsanguination, 16.6% died of early physiologic collapse, 11.1% died of late physiologic collapse, while 38.8% died of nonsurvivable injuries. Patients who died of exsanguination were younger and had the highest RBC/fresh frozen plasma ratio (2.97 [2.24]), although the early physiologic collapse group survived long enough to use the most blood products (p < 0.001). The late physiologic collapse group had significantly fewer penetrating injuries, was older, and had significantly more crystalloid use but received a lower RBC/fresh frozen plasma ratio (1.50 [0.42]). Those who were determined to have a nonsurvivable injury had a lower presenting Glasgow Coma Scale (GCS) score, fewer penetrating injuries, and higher initial blood pressure reflecting a preponderance of nonsurvivable traumatic brain injury. The average survival time for patients with potentially survivable injuries was 2.4 hours versus 18.4 hours for nonsurvivable injuries (p < 0.001). CONCLUSION Severely injured patients requiring MTP have a high mortality rate. However, no studies to date have addressed the cause of death after MTP. Characterization of cause of death will allow targeting of surgical and resuscitative conduct to allow extension of the physiologic reserve time, therefore rendering previously nonsurvivable injury potentially survivable. LEVEL OF EVIDENCE Prognostic study, level III.The Journal of Trauma and Acute Care Surgery 01/2013; 75:S255-S262. · 1.97 Impact Factor
Page 1
Increased Plasma and Platelet to Red Blood Cell Ratios
Improves Outcome in 466 Massively Transfused Civilian
Trauma Patients
John B. Holcomb, MD,* Charles E. Wade, PhD,* Joel E. Michalek, PhD,† Gary B. Chisholm, PhD,†
Lee Ann Zarzabal, MS,† Martin A. Schreiber, MD,‡ Ernest A. Gonzalez, MD,§ Gregory J. Pomper, MD,¶
Jeremy G. Perkins, MD,? Phillip C. Spinella, MD,** Kari L. Williams, RN,* and Myung S. Park, MD*
Objective: To determine the effect of blood component ratios in
massive transfusion (MT), we hypothesized that increased use of
plasma and platelet to red blood cell (RBC) ratios would result in
decreased early hemorrhagic death and this benefit would be sustained
over the ensuing hospitalization.
Summary Background Data: Civilian guidelines for massive trans-
fusion (MT ?10 units of RBC in 24 hours) have typically recommend
a 1:3 ratio of plasma:RBC, whereas optimal platelet:RBC ratios are
unknown. Conversely, military data shows that a plasma:RBC ratio
approaching 1:1 improves long term outcomes in MT combat casual-
ties. There is little consensus on optimal platelet transfusions in either
civilian or military practice. At present, the optimal combinations of
plasma, platelet, and RBCs for MT in civilian patients is unclear.
Methods: Records of 467 MT trauma patients transported from the
scene to 16 level 1 trauma centers between July 2005 and June 2006
were reviewed. One patient who died within 30 minutes of admis-
sion was excluded. Based on high and low plasma and platelet to
RBC ratios, 4 groups were analyzed.
Results: Among 466 MT patients, survival varied by center from
41% to 74%. Mean injury severity score varied by center from 22 to
40; the average of the center means was 33. The plasma:RBC ratio
ranged from 0 to 2.89 (mean ? SD: 0.56 ? 0.35) and the platelets:
RBC ratio ranged from 0 to 2.5 (0.55 ? 0.50). Plasma and platelet
to RBC ratios and injury severity score were predictors of death at
6 hours, 24 hours, and 30 days in multivariate logistic models.
Thirty-day survival was increased in patients with high plasma:RBC
ratio (?1:2) relative to those with low plasma:RBC ratio (?1:2)
(low: 40.4% vs. high: 59.6%, P ? 0.01). Similarly, 30-day survival
was increased in patients with high platelet:RBC ratio (?1:2)
relative to those with low platelet:RBC ratio (?1:2) (low: 40.1% vs.
high: 59.9%, P ? 0.01). The combination of high plasma and high
platelet to RBC ratios were associated with decreased truncal hem-
orrhage, increased 6-hour, 24-hour, and 30-day survival, and in-
creased intensive care unit, ventilator, and hospital-free days (P ?
0.05), with no change in multiple organ failure deaths. Statistical
modeling indicated that a clinical guideline with mean plasma:RBC
ratio equal to 1:1 would encompass 98% of patients within the
optimal 1:2 ratio.
Conclusions: Current transfusion practices and survival rates of MT
patients vary widely among trauma centers. Conventional MT guide-
lines may underestimate the optimal plasma and platelet to RBC ratios.
platelet ratios. Massive transfusion practice guidelines should aim for a
1:1:1 ratio of plasma:platelets:RBCs.
(Ann Surg 2008;248: 447–458)
preventable death.1–5As opposed to the other major causes of
traumatic death, ?head injury and multiple organ failure
(MOF)?, hemorrhagic deaths occur quickly, usually within 2
to 6 hours of injury and often require massive transfusion
(MT) (?10 units of RBCs in 24 hours).6–9Therefore, any
effective resuscitation strategy designed to complement rapid
surgical or angiographic hemostasis must occur early.10–14
Current resuscitation algorithms that support the sequential
use of crystalloids, followed by red blood cells (RBCs) and
then plasma and platelet transfusions have been in wide-
spread use since the 1980s and are codified in the Advanced
Trauma Life Support manual.15Recently, the damage control
resuscitation strategy, equally focused on halting and/or pre-
venting the lethal triad of coagulopathy, acidosis, and hypo-
thermia, has challenged traditional thinking on early resusci-
tation strategies.16–18Damage control resuscitation advocates
ncontrolled hemorrhage after both civilian and combat
traumatic injury is the most common cause of potentially
From the *United States Army Institute of Surgical Research, Ft Sam
Houston, TX; †Department of Epidemiology and Biostatistics, Univer-
sity of Texas Health Science Center, San Antonio, TX; ‡Department of
Trauma/Emergency and General Surgery Oregon Health and Science
University, Portland, OR; §Department of Surgery, University of Texas
Health Science Center, Houston, TX; ¶Department of Pathology, Wake
Forest University School of Medicine, Winston Salem, NC; ?Walter Reed
Army Medical Center, Bethesda, MD; and **Connecticut Children's
Medical Center, Hartford, CT.
The views and opinions expressed in this manuscript are those of the authors
and do not reflect the official policy or position of the Army Medical
Department, Department of the Army, the Department of Defense, or the
United States Government.
Army Institute of Surgical Research, 3400 Rawley E, Chambers Avenue,
Fort Sam Houston, TX 78234. E-mail: email@example.com.
Copyright © 2008 by Lippincott Williams & Wilkins
DOI: 10.1097/SLA.0b013e318185a9ad
Annals of Surgery • Volume 248, Number 3, September 2008
Page 2
transfusing earlier and increased amounts of plasma and
platelets along with the first units of RBCs while simulta-
neously minimizing crystalloid use in patients who are pre-
dicted to require a MT.16–18
Because coagulopathy was believed to develop from di-
lution and hypothermia over the course of several hours, stan-
dard resuscitation approaches emphasize the use of crystalloids
and RBCs to improve cardiac output and oxygen delivery.19,20
The use of plasma and platelets is reserved for patients with
persistent hypotension unresponsive to crystalloid infusion,
transfusion ?6 units of RBCs, documented abnormal coagula-
In 2003, Brohi et al and MacCloud et al separately described the
early coagulopathy of trauma that is present on admission to the
emergency department (ED) in 25% of patients and associated
with increased mortality.21,22With this new information in
mind, clinicians treating combat injuries in Iraq and Afghanistan
documented improved outcomes after MT, using nontraditional
resuscitation strategies.23This military experience suggested
that an increased plasma:RBC ratio would both decrease early
hemorrhagic death and improve long term survival. The lack of
large controlled studies or even retrospective studies with com-
parison groups has perpetuated a wide variability among centers
in massive transfusion protocols. Classic resuscitation strategies
have been called into question by 5 recent findings: (1) recent
data documenting the adverse effects of excessive crystalloid
use,24–29(2) patients in shock are coagulopathic upon admission
to the emergency department and have increased mortality,21,22
(3) MT patients represent a small percentage of admissions
(3%), yet have a 30% to 60% mortality,30,31(4) truncal hemor-
rhage represents a major cause of potentially preventable
coagulopathic upon arrival to the intensive care units (ICUs).32
Although these findings have been explored in several recent
studies, there is still no broad consensus on optimal plasma and
platelet ratios for civilian trauma patients.33–39For those patients
who present in shock and are predicted to require MT, a change
from the classic resuscitation approach is in order.
For massively transfused combat trauma patients, in-
creased plasma:RBC ratios of ?1:2 have been associated
with improved long term outcomes.23However, an optimal
plasma and platelet to RBC ratio has not been defined for
civilian trauma patients. Our objective was to describe the
present MT practices at level 1 trauma centers and to identify
the optimal combination of plasma, platelets, and RBCs after
civilian trauma. We hypothesized that increased plasma and
platelet to RBC ratios would result in decreased early hem-
orrhagic death and that this benefit would be sustained over
the ensuing hospitalization.
Data for this study came from a retrospective multi-
center Institutional Review Board approved trial of transfused
trauma patients admitted to 16 level 1 trauma centers between
July 2005 and June 2006. Included in the study were adult
trauma patients who arrived from the scene and received at
least 1 unit of RBC in the ED, irrespective of mechanism of
injury. Of the 1574 patients in the study, 467 received a
massive transfusion (MT, ?10 units of RBCs in 24 hours).
To remove the bias that may have been introduced by plasma
or platelet unavailability, all patients who died within 30
minutes of arrival to the ED were excluded (n ? 1). Demo-
graphic, transfusion, laboratory, time-to-death after ED ad-
mission, and outcome data were collected from each site in a
uniform format and entered into a database at the Department
of Epidemiology and Biostatistics, University of Texas
Health Science Center, San Antonio, TX. All time-to-death
data were calculated based on the time of admission to the
ED. Units of RBCs, platelets, and plasma were adjusted to
standard units and totaled at 6 and 24 hours after admission.
Crystalloid and colloid amounts were similarly recorded.
Ventilator, ICU, and hospital-free days were calculated based
on a stay of 30 days. Cause of death was categorized as
multiple organ failure, truncal hemorrhage, head injury, air-
way problems, or others, and validated by the senior inves-
tigator at each site. The initial plasma:RBC ratios and plate-
lets:RBC ratios were determined based on the data from
previous publications.19,23,40Data integrity was personally
verified by one of the authors (KW).
tabulated by category of plasma:RBC ratio (low: ?1:2, high:
?1:2) and platelet:RBC ratio (low: ?1:2, high: ?1:2). The
study cohort was partitioned into 4 groups based on plasma:
RBC and platelet:RBC category (1: high-high, 2: high-low, 3:
low-high, 4: low-low). The significance of the relationship
between mortality status (survived, died) and category of plasma
and platelet to RBC ratio was assessed with logistic regression
models in terms of plasma:RBC ratio category, platelet:RBC
category, the interaction of the plasma:RBC ratio category, and
platelet:RBC ratio category (data not shown). These indepen-
dent main effects and interaction models motivated the data
summaries shown. The relationship between survival time and
plasma and platelet RBC ratio (group) was assessed with
recommended plasma:RBC ratios in future applications of these
results, we empirically estimated a target mean plasma:RBC
ratio so that 98% of the values would exceed 1:2 by modeling
the distribution of the ratio as ??r? and setting the 0.02 quantile
equal to 0.5 (or, equivalently, plasma:RBC ? 1:2). With this
the ratio distribution would shift to the right by an amount (?).
The mean of the new distribution (the target mean) would then
be the mean before the guidance (?) plus the shift, giving a
target mean of ? ? ?. The shift parameter, ?, was chosen so
approximately 0.5. We investigated heterogeneity in relation
between survival to 30 days and ratios (plasma:RBC or platelet:
RBC) with center using the following: (a) least squares regres-
sion of the proportion surviving 30 days within center in terms
of the mean ratios within center and (b) an accelerated failure
time model of time-to-death in terms of center, the ratios,
covariates, and first-order interactions. All statistical testing was
2-sided with a significance level of 5%, and SAS version 9.1.3
Holcomb et al
Annals of Surgery • Volume 248, Number 3, September 2008
© 2008 Lippincott Williams & Wilkins
Page 3
out. All graphical presentations were created using R version
Of the 1574 patients who received at least 1 unit of blood,
467 were massively transfused. After excluding 1 patient who
died within 30 minutes of admission, the study population was
466 patients (Table 1). The mean injury severity score (ISS)
varied by center from 22 to 40; the average of the center means
was 33. Survival varied by center from 41% to 74%. Using least
squares regression the proportion surviving 30 days varied
After adjustment for plasma:RBC (continuously distributed),
ISS, and platelets, significant variation in the time-to-death
with center was found (P ? 0.02, df ? 15, data not shown),
documenting a significant center effect (Fig. 1). No signifi-
cant correlation between survival and platelet:RBC ratio with
center was found.
The patient plasma:RBC ratio ranged from 0 to 2.89
(mean ? SD: 0.56 ? 0.35), and the platelets:RBC ratio
ranged from 0 to 2.5 (0.55 ? 0.50). A plasma:RBC ratio of
?1:2 was associated with improved 30-day survival (40.4%
vs. 59.6%, P ? 0.01). Similarly, a platelet:RBC ratio of ?1:2
was associated with improved 30-day survival (40.1% vs.
59.9%, P ? 0.01). Plasma and platelet to RBC ratios ?1:2
were found to be optimal. Plasma and platelet to RBC ratios
were independent predictors of death at 6 and 24 hours and 30
days. These 2 treatment groups were then expanded into 4 in
a 2-by-2 factorial layout (Table 2). Group 1 was the patients
receiving the following: (1) high plasma and platelet ratio
(n? 151); (2) high plasma and low platelet (n ? 101); (3) low
plasma and high platelet (n ? 83); and (4) low plasma and
low platelet ratio (n ? 131). The 30-day survival was 59%,
and within group survival was: group 1 ? 73%; group 2 ?
54%; group 3 ? 67%; and group 4 ? 43%, (P ? 0.001).
Kaplan-Meier analysis showed that a significant separation of
groups occurred within 6 and 24 hours (P ? 0.001) and that
group 1 had increased survival compared with the others at 6
and 24 hours (P ? 0.001, Fig. 2). The overall 24-hour
difference was sustained through 30 days (P ? 0.001, Fig. 3);
however, at 30 days there was no difference between groups
1 and 3 (P ? 0.08).
Patients were severely injured, acidotic, and coagulo-
pathic on admission (Table 1). Although several demographic
variables were different between groups, these differences were
scattered between the groups and were not considered clinically
significant (Table 2). By study design, differences were seen in
administration of components between groups, although there
were no differences in transfused RBCs (Table 3). The 2 groups
that received high platelets demonstrated increased ventilator,
ICU, and hospital-free days (P ? 0.01, Table 4).
ISS and maximal regional abbreviated injury scores were
not different between groups (Table 2). Specifically, the maxi-
different between groups (P ? 0.26 and P ? 0.58, respectively).
The mortality benefit seen in group 1 was attributed to a
reduction in truncal hemorrhage deaths to 10% compared with
25%, 22%, and 44% for the other groups, respectively (P ?
0.001, Table 4). There were no significant differences in deaths
because of MOF, head injury, airway problems, or other causes
between groups (Table 4). Of those who died, median time-to-
group 2 ? 18 hours; group 3 ? 6 hours; and group 4 ? 4 hours
(P ? 001, Table 4).
lines for MT or even future prospective trials, a statistical model
was constructed. To achieve an optimal plasma:RBC ratio
(?1:2) in 98% of massively transfused patients, a ? model and
a location shift was assumed. The distribution of the plasma:
RBC ratio was modeled as ? with scale and shape parameters of
0.268 and 2.09, respectively, and mean 0.56. A location shift of
Demographic Characteristics for MT Patients
Overall survival
Age (yr)
Men (%)
Blunt injury, (%)
Admission SBP (mm Hg)
Heart rate (bpm)
Admission base deficit
Admission temperature (°C)
Admission GCS
Injury severity score
39 ? 18
107 ? 33
114 ? 28
?11.7 ? 7.7
7.2 ? 0.2
1.6 ? 0.9
36 ? 1.3
9 ? 5
32 ? 16
SBP indicates systolic blood pressure; INR, international normalized ratio; GCS,
glasgow coma score.
FIGURE 1. Bubble plot of the relationship of mean center
plasma to RBC ratio to survival. Size of circles represents the
percentage of MT patients contributed by each center. Col-
ors indicate 3 levels of injury severity scores.
Annals of Surgery • Volume 248, Number 3, September 2008Blood Component Ratios in Civilian Trauma Patients
© 2008 Lippincott Williams & Wilkins
Page 4
0.512 produced a new ? distribution with scale and shape
parameters of 0.104 and 10.23, 0.02 quantile? 0.5, and mean?
1.07; for simplicity, we rounded the postshift mean to 1.0. This
model suggests that if, in the future, the mean plasma:RBC ratio
goal is 1:1, then approximately 98% of patients will receive a
plasma:RBC ratio of at least 1:2. Thus a target mean plasma:
RBC ratio of 1:1 is suggested. A corresponding target mean of
1:1 for the platelet:RBC ratio is also suggested, (data not
In this multicenter MT study, the largest from level 1
trauma centers, the overall survival was 59% (range by center,
41%-74%). Overall survival within the 4 ratio groups was
plasma and platelets. These results are similar to the data from
combat casualties (92% penetrating injury) showing improved
survival (35%-81%) associated with increased plasma ratios.23
Survival benefit in the present study was seen predominantly in
Demographic Characteristics by Plasma and Platelet Ratios
High PlasmaLow Plasma
High Platelets
Low Platelets
(n ? 101)
High Platelets
(n ? 83)
Low Platelets
(n ? 131)
Age (yr)
Men (%)
Blunt injury (%)
Admission SBP (mm Hg)
Heart rate (bpm)
Admission base deficit (meq/L)
Admission temperature (°C)
Admission platelet count
Admission GCS
Injury severity score
Maximum head AIS
Maximum chest AIS
36 ? 18
110 ? 34
118 ? 29
?12 ? 9
7.2 ? 0.2
1.6 ? 0.7
36 ? 1
9 ? 5
30 ? 14
2 ? 2
2 ? 2
41 ? 18
114 ? 35
114 ? 27
?10 ? 6
7.2 ? 0.2
1.7 ? 1
36 ? 2
8 ? 6
35 ? 18
2 ? 2
2 ? 2
42 ? 16
101 ? 30
113 ? 26
?11 ? 6
7.2 ? 0.2
1.5 ? 1.5
36 ? 1
10 ? 6
32 ? 17
2 ? 2
2 ? 2
40 ? 19
100 ? 31
110 ? 27
?13 ? 7
7.1 ? 0.2
1.5 ? 0.6
36 ? 2
9 ? 6
32 ? 17
1 ? 2
2 ? 2
High plasma or platelet to RBC ratio ?1:2. Low plasma or platelet to RBC ratio ?1:2.
AIS indicates Abbreviated Injury Score.
FIGURE 2. Kaplan-Meier survival plot for the first 24 hours
after admission for the 4 groups (high plasma (FFPH) or
platelet (PltH) to RBC ratio ?1:2, low plasma (FFPL) or plate-
let (PltL) to RBC ratio ?1:2).
FIGURE 3. Kaplan-Meier survival plot for the first 30 days
after admission for the 4 groups (high plasma (FFPH) or
platelet (PltH) to RBC ratio ?1:2, low plasma (FFPL) or plate-
let (PltL) to RBC ratio ?1:2).
Holcomb et al
Annals of Surgery • Volume 248, Number 3, September 2008
© 2008 Lippincott Williams & Wilkins
Page 5
patients with truncal hemorrhage, with most of the improvement
seen by 6 hours.
Trauma patients largely die of truncal hemorrhage, head
injury, or MOF. Overall survival rates of patients admitted to
civilian trauma centers are approximately 96%. Those who do
not receive a transfusion have a survival of ?99%, whereas the
2% that are massively transfused have a survival of ?60%.30,31
Autopsy studies demonstrate that uncontrolled truncal hemor-
rhage is responsible for 45% to 85% of potentially preventable
death.1–5Hemorrhagic truncal death after admission occurs very
quickly and prolonged shock increases MOF and late death.8,41
Therefore, new resuscitation paradigms must be implemented to
improve outcomes from truncal hemorrhage.
After World War II it was recognized that hemorrhagic
shock was optimally treated with whole blood replacement.42
However, in 1976, Carrico et al stated that the optimal
resuscitation of hemorrhagic shock patients consisted of 1–2
L of lactated ringers, accompanied by whole blood transfu-
sion over the first 45 minutes after ED arrival.43By the mid
1980s plasma, platelets, and cryoprecipitate had been re-
moved from red cells, yet resuscitation strategies for patients
in hemorrhagic shock had not been changed to account for the
new blood components, focusing on rapid infusion of warm
crystalloid and RBCs. We continued to transfuse RBC units
as if they were whole blood, and increasingly large amounts
of crystalloid were used to maintain blood pressure and
oxygen delivery.44,45Neither RBCs nor crystalloid contain
procoagulant components and this practice has likely exac-
erbated the early coagulopathy of trauma. There were no
large prospective studies of these changes in transfusion
products or practices, and the retrospective studies did not
construct comparison groups to examine different amounts or
ratios of the various blood products.46–48Concomitant to the
changes in component therapy and increased crystalloid use,
acute respiratory distress syndrome, and abdominal and ex-
tremity compartment syndromes were reported with increas-
Blood Component Transfusions by Plasma and Platelet Ratios
High Plasma Low Plasma
High Platelets
(n ? 151)
Low Platelets
(n ? 101)
High Platelets
(n ? 83)
Low Platelets
(n ? 131)
FFP (units)
Platelets (units)
RBC (units)
Crystalloid (L)
FFP:RBC ratio
Platelet:RBC ratio
Crystalloid:RBC ratio
Received rFVIIa (%)
17 ? 12
20 ? 16
22 ? 17
14 ? 10
0.8 ? 0.3
0.9 ? 0.4
0.8 ? 0.5
34 (22)
16 ? 10
5 ? 6
21 ? 12
13 ? 7
0.8 ? 0.3
0.2 ? 0.2
0.8 ? 0.6
11 (11)
7 ? 5
18 ? 10
21 ? 11
17 ? 12
0.3 ? 0.1
0.9 ? 0.4
0.9 ? 0.6
21 (25)
6 ? 6
4 ? 6
21 ? 12
11 ? 10
0.2 ? 0.1
0.1 ? 0.2
0.6 ? 0.5
15 (12)
High plasma or platelet to RBC ratio ?1:2. Low plasma or platelet to RBC ratio ?1:2.
FFP indicates fresh frozen plasma.
Survival, Cause of Death, and Clinical Outcomes by Plasma and Platelet Ratio
High Plasma (%)Low Plasma (%)
High Platelets
(n ? 151)
Low Platelets
(n ? 101)
High Platelets
(n ? 83)
Low Platelets
(n ? 83)
Survival (%)
Survival at 6 h
Survival at 24 h
Survival at 30 d
Median time-to-death, (hours)
Cause of death
Truncal hemorrhage (%)
Head injury
Clinical outcomes
Hospital-free days
ICU-free days
Ventilator-free days
6 ? 8
5 ? 7
6 ? 8
3 ? 6
3 ? 6
2 ? 5
5 ? 8
6 ? 7
7 ? 8
3 ? 7
4 ? 7
4 ? 7
High plasma- or platelet-to-RBC ratio ?1:2. Low plasma- or platelet-to-RBC ratio ?1:2.
Annals of Surgery • Volume 248, Number 3, September 2008Blood Component Ratios in Civilian Trauma Patients
© 2008 Lippincott Williams & Wilkins
Page 6
ing frequency, whereas damage control surgery strategies
evolved to manage coagulopathic bleeding.49–51It is likely
that some of acute respiratory distress syndrome and much of
the compartment syndromes represent iatrogenic injury and
can be prevented by more appropriate use of crystalloids and
blood component therapy.24,52–55
In 2003, Brohi et al and MacCloud et al demonstrated
that 25% of trauma patients arriving in the ED are coagulo-
pathic, (defined by prolonged prothrombin time or partial
thromboplastin time) and have increased mortality.21,23
Based on mathematical modeling, recommendations were
also made that increased ratios of plasma and platelets to
RBCs (2:3) should be used to prevent iatrogenic hemodilu-
tionandprogressive coagulopathy.56,57
Gonzalez et al recommended that increased plasma be used
earlier in trauma resuscitation, based on persistent coagulopa-
thy associated with increased mortality.32Finally, reprising
the editorial by Moore and Shires in 1967 asking for moder-
ation in the use of crystalloid,58multiple authors have re-
cently described the proinflammatory characteristics of crys-
Others have described decreased abdominal
compartment syndrome and death24or increased ventilator and
ICU-free days29simply by limiting the amount of crystalloid
infused early after admission. Interestingly, plasma has been
shown to be less inflammatory than artificial colloid, albumin, or
lactated ringers in a swine study of hemorrhagic shock.28In the
current study, patients in groups 1 and 3 received more overall
rate of infusion was likely higher in groups 2 and 4. Moore et al
the potential changes in outcomes that could occur simply by
altering the rates and amounts of resuscitation fluids.59,60Many
authors have focused on altering rates and amounts of crystal-
loids.60–64We feel that the same successful approach should be
applied to blood products.23,65–71
Recent reviews of massive transfusion protocols for
trauma patients in the United States and Europe recommend
benefits of increased plasma use in the MT population likely
come from several areas, including replacing coagulation pro-
teins, which prevents or treats the coagulopathy associated with
hemorrhage and shock.74–77Although the improved outcomes
associated with decreasing crystalloid and increased plasma and
platelets use in coagulopathic patients makes intuitive sense, we
do not suggest that the observed improvement in mortality is
simply a reversal or prevention of early coagulopathy alone. It is
likely that differences in injury, endothelial structure, alterations
in thrombomodulin and protein C, adhesion, systemic inflam-
mation, consumption, hemodilution, acidosis, hypothermia, hy-
pocalcemia, fibrinolysis, increased platelet counts and plasma
proteins, genetic variation, and many other mechanisms are
Each unit of plasma contains approximately 400 mg of
fibrinogen, an essential protein for clot formation shown to
decrease early in patients with hemorrhage.80–83Plasma also
has the additional benefit of acting as a buffer, potentially
improving the acid base status of patients who are already
acidotic.84This is in contrast to the use of crystalloids that are
acidic in nature and proinflammatory.26,27Lastly, plasma and
RBCs are both excellent volume expanders. As the risk of
blood-borne diseases becomes ever smaller, the increased use
of plasma as a volume expander in the small percentage of
patients requiring MT seems indicated, reserving RBCs to
treat oxygen debt and crystalloid as a smaller component of
the resuscitation algorithm.
Improved outcomes after earlier transfusion of increased
amounts of blood products are documented in 2 retrospective
studies.23,71Johansson et al reported that increased amounts of
plasma and platelets given in the operating room in predeter-
mined ratios for patients with ruptured aortic aneurysms im-
proved survival (44% vs. 66%, P ? 0.05).71A platelet count of
?100 ? 109upon arrival in the ICU was associated with
improved survival. The survival difference appeared in the first
4 days and was sustained through 30 days, (P ? 0.02). Borgman
et al described their improved results in combat trauma patients
by transfusing increased amounts of plasma.23They compared
outcomes of similarly injured patients who received varying
ratios of plasma:RBCs. In ratios approaching 1:1, long term
mortality was 19%, 1:3 was 35%, and 1:8 was 60% (P ? 0.05).
Time-to-death was 2 to 4 hours and largely from truncal hem-
orrhage in the 2 groups receiving less plasma. Platelet transfu-
sions were not routinely available in the combat theater during
the data accrual period. Questions remained if similar results
would be seen in a civilian trauma population, with different
blood transfusions. These important papers by Johansson et al71
and Borgman et al23have sparked a renewed interest in the use
of new combinations of existing blood components and more
data are forthcoming.33–39
These papers have brought to the forefront the contro-
versial issue of predetermined ratios for use in the early
massive transfusion of trauma patients.85–87Although, ide-
ally, every product transfused would be based on a laboratory
value and real time expert consultation with transfusion
specialists, this is simply not possible in the rapidly bleeding
hemorrhagic shock patient. Unfortunately, without a well-
defined massive transfusion protocol, inadequate amounts of
plasma and platelets are frequently transfused, with the pa-
tient suffering the negative consequences.86,87In recognition
of the many and varied human and logistical factors involved
in delivering the appropriate ratio of products, many centers
have developed a "push" rather than a "pull" approach.68
Essentially, this means streamlining administrative tasks and
paperwork to deliver blood products as quickly as possible.
Once initiated, this approach keeps fixed ratios of plasma,
platelets, and RBCs coming from the blood bank to the
bedside until stopped by the clinician, ensuring that appro-
priate ratios and quantities are transfused. Once established,
through careful discussion with all parties involved in mas-
sive transfusion, this system works well.
Dilutional thrombocytopenia (platelet counts ? 100 ?
109/L) as the major cause of microvascular bleeding, has tended
to develop only after MT patients received 18-20 units of stored
whole blood.88–90In addition to thrombocytopenia, intrinsic
platelet function is impaired by acidosis and hypothermia, which
can develop in severely injured patients who require MT.91–93
Holcomb et al
Annals of Surgery • Volume 248, Number 3, September 2008
© 2008 Lippincott Williams & Wilkins
Page 7
The currently recommended platelet transfusion threshold is 50
to 100 ? 109/L in actively bleeding patients.94,95The impor-
tance of platelets in MT was studied in a single randomized trial
that noted no difference in microvascular bleeding, though the
platelet group received a low platelet:RBC ratio of 0.5:1.96Later
studies found that a 0.8:1 ratio was associated with improved
survival.19,40,56,57In summary, the available data are sparse on
when platelets should be started and the optimal ratio. However,
when comparisons are made, a ratio approaching 1:1 is associ-
ated with improved survival.
Most expert recommendations are based on level IV data
from elective surgery patients, and suggest guiding transfusions
based on laboratory values. Unfortunately, most of these critical
laboratory threshold values occur after a blood loss equaling 1.5
to 2 blood volumes.97–100It is interesting that many of the
patients in the current study were coagulopathic upon arrival
(international normalized ratio ?1.5) and met the laboratory
definition for requiring plasma transfusion upon arrival in the
ED. Additionally, given the rate of resuscitation in MT trauma
patients, laboratory parameters can rarely be used to guide blood
component therapy. Rather, their need is judged clinically,
highlighting the need to adhere to established MT protocols.87
To our knowledge these data represent the first to report
outcomes of plasma and platelet transfusion together. Based
on data from others describing survival benefit by transfusing
more versus less plasma and platelets, high and low ratios
were explored in the massive transfusion dataset. By com-
paring ratios starting at 1:1 and continuing through 1:8, we
determined that survival was improved at 6 and 24 hours and
30 days with ratios ?1:2 for both plasma and platelets. We
explored the relationship of plasma and platelets to RBC
ratios by creating 4 possible groups with the 2 components.
Among ratio groups, overall survival ranged from 41% to
71%, with essentially all the difference occurring in the first
6 hours after admission because of a decrease in fatal truncal
hemorrhage. Survival differences persisted through 30 days
(P ? 0.001). Despite the significantly increased plasma and
platelet transfusion amounts, there was no difference in MOF
as a cause of death between groups (5%, P ? 0.45). These
findings support the use of increased amounts of plasma and
platelets early in the course of care in patients predicted to
require massive transfusion.
Concern exists that transfusing increased amounts of
plasma and platelets will increase the incidence of transfusion
related acute lung injury (TRALI) and MOF.100–104These
concerns are reasonable, but must be placed within the appro-
priate clinical context. Massive transfusion patients, although
comprising only 3% of all trauma admissions, have a mortality
of 30% to 60%, whereas TRALI occurs anywhere from 1 in 5 to
10,000 transfusions, is currently managed with ventilator sup-
port, usually resolves in 24 hours and is fatal in only 6% to 9%
of cases.103–105Using the above numbers, there are ?5000
trauma patients who could be saved at the risk of ?10 cases of
fatal TRALI per year. There is the obvious conundrum in this
study of transfusing proinflammatory plasma and platelets that
are associated with improved outcomes in critically injured
trauma patients, without increased fatal MOF.
associated with a retrospective design. The 4 groups were not
equal in a limited number of demographic parameters; however,
these inequalities were distributed across the groups and consid-
ered clinically insignificant. The timing of the various compo-
nents of the massive transfusion, (crystalloid, RBCs, plasma,
and platelets) were unknown, so although the final ratios were
similar within groups there may have been important differences
in the order and time when the products were actually infused.
Depending on the collection method, platelet units can contain a
significant amount of plasma.75As a result, the amount of
plasma that was transfused in the patients who received platelets
was underestimated and may have contributed to the similar
30-day survival rates in groups 1 and 3. Although the primary
end point was mortality after admission, and causes of death
were defined before data collection, MOF was not explicitly
defined. However, given the types of centers, lack of overlap in
categories, and the broad agreement of definitions, we feel that
the conclusions are valid. There was no data collected on
nonfatal diagnoses, complications, infections, or procedures;
however, ICU, ventilator, and hospital-free days were consid-
ered a surrogate and outcomes for the high platelet groups were
improved compared with low platelet groups (P ? 0.05). Fi-
nally, the effect of multiple unmeasured confounding variables
must be considered as at least a partial explanation for the study
The current study has several important strengths. Our
findings are in agreement with and extend the observations of
other authors.23,32–39This study was unique because of the
measurement of plasma and platelets reflecting actual clinical
practice, and the availability of time and cause of death from
admission and blood products in the first 6 and 24 hours. To our
knowledge, these data represent the largest MT study and the
first to study plasma and platelet transfusion data together along
with high and low ratio comparison groups. The type of centers
contributing data for this study lends validity to the conclusions,
despite the retrospective study design and significant variability
between centers. Survival was improved with the use of in-
the beneficial 1:2 ratio is achieved 98% of the time (2 standard
deviations), one should plan for a 1:1 goal of mean plasma:RBC
ratio. Despite the significantly increased plasma and platelet
transfusion amounts, there was no difference in MOF as a cause
of death between the 4 groups. Though trauma centers are
required to have a MT protocol,106data are sparse on which to
base quality clinical practice guidelines. To maximize the ben-
efits while minimizing the risks of using increased blood prod-
ucts earlier in the care of MT trauma patients, many centers are
fusing with defined blood product ratios and with decreased
crystalloid rates. The data in the current study, together with the
recent military experience, are compelling and have served to
stimulate critical reexamination of current transfusion practice.
The authors thank The Trauma Outcomes Group
(TOG); JB Holcomb, CE Wade, MS Park, and KL Williams
from the United States Army Institute of Surgical Research
Annals of Surgery • Volume 248, Number 3, September 2008 Blood Component Ratios in Civilian Trauma Patients
© 2008 Lippincott Williams & Wilkins
Page 8
and Brooke Army Medical Center, Ft Sam Houston TX; EA
Gonzalez and RA Kozar from the University of Texas Health
Science Center, Houston, TX; JE Michalek, GB Chisholm, LA
Zarzabal, RM Stewart, and SM Cohn from the University of
Texas Health Science Center, San Antonio, TX; JP Minei, T
and O'Keefe UT from the Southwestern Medical Center,
Dallas, TX; MA Schreiber and B Tieu from the Oregon
Health and Science University, Portland OR; EM Bulger
from the University of Washington, Seattle, WA; S Brundage
from the Stanford University Medical Center, CA; HM Cryer
and A Tillou from the University of California and Los
Angeles, CA; G Beilman and M Thorson from the University
of Minnesota, Rochester, MN; KJ Brasel from the Medical
College of Wisconsin, Milwaukee, WI; J Johannigman and P
Muskat from the University Hospital Cincinnati, OH; AB
Peitzman and L Alarcon from the University of Pittsburgh
Medical Center, Pittsburg, PA; G Vercruysse and J MacLeod
Emory from the University School of Medicine, Atlanta, GA;
GJ Pomper and PR Miller from the Wake Forest School of
Medicine, Winston Salem, NC; MA De Moya and MU from
Butt Massachusetts General Hospital, Boston, MA; and K
Brohi and T Konig from Royal London Hospital, England.
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Annals of Surgery • Volume 248, Number 3, September 2008Blood Component Ratios in Civilian Trauma Patients
© 2008 Lippincott Williams & Wilkins
Page 10
94. Contreras M. Consensus confe ´rence on platelet transfusion: final state-
ment. Vox Sang. 1998;75:173–174.
95. Stainsby D, MacLennan S, Thomas D, et al. Guidelines on the man-
agement of massive blood loss. Br J Haematol. 2006;135:634–641.
96. Reed RL II, Ciavarella D, Heimbach DM, et al. Prophylactic platelet
administration during massive transfusion. A prospective, randomized,
double-blind clinical study. Ann Surg. 1986;203:40–48.
97. British Committee for Standards in Haematology, Blood Transfusion
Task Force. Guidelines for the use of platelet transfusions. Br J
Haematol. 2003;122:10–23.
98. O'Shaughnessy DF, Atterbury C, Bolton Maggs P, et al. ; British
Committee for Standards in Haematology, Blood Transfusion Task
Force. Guidelines for the use of fresh-frozen plasma, cryoprecipitate
and cryosupernatant. Br J Haematol. 2004;126:11–28.
99. Practice guidelines for perioperative blood transfusion and adjuvant
therapies: an updated report by the American Society of Anesthesiol-
ogists Task Force on perioperative blood transfusion and adjuvant
therapies. Anesthesiology. 2006;105:198-208.
100. Stanworth SJ. The evidence-based use of FFP and cryoprecipitate for
abnormalities of coagulation tests and clinical coagulopathy. Hematol-
ogy Am Soc Hematol Educ Program. 2007;2007:179–186.
101. MacLennan S, Williamson LM. Risks of fresh frozen plasma and
platelets. J Trauma. 2006;60:S46–S50.
102. Norda R, Tynell E, Akerblom O. Cumulative risks of early fresh frozen
plasma, cryoprecipitate and platelet transfusion in Europe. J Trauma.
103. Flesland O. A comparison of complication rates based on published
haemovigilance data. Intensive Care Med. 2007;33:S17–S21.
104. Bux J. Transfusion-related acute lung injury (TRALI): a serious ad-
verse event of blood transfusion. Vox Sang. 2005;89:1–10.
105. Bux J, Sachs UJ. The pathogenesis of transfusion-related acute lung
injury (TRALI). Br J Haematol. 2007;136:788–799.
106. Resources for the Optimal Care of the Injured Patient. American
College of Surgeons Committee on Trauma, American College of
Surgeons. Chicago, Illinois. 2006;67.
DR. ERNEST E. MOORE, JR (DENVER, COLORADO): Many
thousands of critically wounded soldiers from the ongoing con-
flicts in the Middle East are alive today because of Colonel
Holcomb's unique proclivity to bridge evolving trauma care
strategies in civilian and military environments. As a military
surgeon, John had the foresight to study damage control in the
civilian trauma centers in Houston and successfully exported
these principles to the battlefields of Iraq and Afghanistan,
where he continues to extend the frontiers.
The current report, motivated by compelling military
data, indicates a survival benefit of preemptive fresh frozen
plasma given at a ratio of 1:1 with every transfused unit of red
cells. Colonel Holcomb has built an impressive collaboration
with 16 civilian level 1 trauma centers to test the hypothesis
that presumptive platelets and FFP will improve survival in
injured patients requiring a massive transfusion. Based on
systematic analyses of their extensive database from 466
qualified patients, John and his colleagues conclude that a
1:1:1 ratio of FFP to platelets to red cells should be consid-
ered the standard for civilian practice.
These finding have profound implications as we strug-
gle to develop safe and cost-effective transfusion policies,
and are particularly timely in the wake of recent reports of
influential journals incriminating overzealous FFP and plate-
let transfusion in the pathogenesis of acute lung injury.
Similar to stored red cells, these blood products are expensive
and contain quantities of legitimate inflammatory mediators
such as activated complement and fibrin degradation products
in FFP, soluble CD 40 ligand RANTES, and arachidonic in
platelets. Furthermore, the composition of FFP and platelets
varies considerably depending on retrieval method and stor-
age duration.
With that brief background, I have several items for the
authors to consider, although none of these will be new to
these experts.
First, one of the perplexing issues of this study and other
recent similar efforts is a lack of a documented mechanistic link.
In the current scenario, preemptive FFP and platelets were
administered to attenuate postinjury coagulopathy, yet evolving
data suggest that the initial coagulopathy in severe trauma is
independent of clotting factor insufficiency.
You have nicely illustrated that the separation in deaths
occur within the first 3 hours. Thus, to pursue your hypothesis
on a scientific basis, it would seem important to (a) analyze
transfusion ratios within the first 1, 2, and 3 hours and (b) to
assess the impact of these ratios on coagulation status during
this critical period.
Is early improvement in coagulation function an inde-
pendent variable for survival? More specifically, did patients
die of uncontrollable torso blood loss that was fundamentally
unrelated to their coagulation status? Perhaps the ability to
achieve higher FFP and platelet ratios is simply a marker of
a more favorable injury pattern. Did you exclude patients
who were given activated factor VII? Was there a difference
in blunt versus penetrating trauma? Did you examine the rate
of red cell transfusion during the first hour of arrival?
I recall the insightful words of a blood banker, Dr. Ben
Galloway, when as a junior attending I would request fresh
whole blood for a trauma patient at Denver General in the
1970s and he would politely respond, "is the patient dying
because they are bleeding or bleeding because they are
dying?" Modern urban EMS can certainly deliver patients
who are in the process of dying irrespective of our efforts.
Alternatively, the benefits of early plasma may be because of
other effects, such as colloidal properties or even binding
lipid mediators.
This stimulating study prompts many interesting ques-
tions, but I will conclude with a focus on the future. I would
respectfully review this meticulous investigation as tanta-
mount to a well-done meta-analysis, which we have learned
does not provide a definitive answer to a complex question,
but rather the genesis of a hypothesis to be tested in a rigorous
controlled trial.
In that light, how would you propose such a trial to
determine if 1:1:1 is optimal? Will you attempt to study FFP
and platelets concurrently? How do you imagine activated
factor VII, because this will likely become integral in massive
transfusion protocols. Will point-of-care testing of coagula-
Holcomb et al
Annals of Surgery • Volume 248, Number 3, September 2008
© 2008 Lippincott Williams & Wilkins
Page 11
tion status such as thromboelastography play an important
role in this pivotal study?
DR. DONALD D. TRUNKEY (PORTLAND, OREGON): In doing
these massive transfusion protocols, there is another issue, and
that is the age of the packed red blood cells. Did you look at this
in this multi-institutional study? Furthermore, if you get down to
common horse sense, a 1:1:1 ratio is called whole blood. Why,
then, do we not give whole blood?
DR. HOWARD R. CHAMPION (BETHESDA, MARYLAND): Colo-
nel Holcomb's data are somewhat disturbing but are certainly
supported by my own observations as chair of a Data Safety
Board for an international resuscitation research initiative. The
variation in clinical practice from one center to another is of
great concern, as is the problem regarding control for case mix
differences and confounding variables. Together these issues
raise the question as to whether one can draw viable scientific
conclusions from data from acute resuscitation research.
It seems we need not only to get some agreement on
resuscitation protocols but also on the actual process within a
trauma center by which we get timely and appropriate deliv-
ery of coagulation factors to the patient. Thus, we need to
control for the therapeutics and for the complexities of injury
in these patients if we are to study them successfully.
Obviously in this, timing is everything. When you look at the
plasma and platelets as related to the red cells? I have had
personal experience with a ratio that was close to that but it was
so weighted toward the end that you wind up with a patient that
is profoundly coagulopathic, and by the time you pump in all the
fresh frozen plasma and platelets, it is probably too late. Do you
have an idea about the relative timing of the components?
DR. JOHN B.HOLCOMB (FORT SAM HOUSTON, TEXAS): There
is no data driven mechanism from this retrospective clinical
study. We do suggest some possibilities in the paper and I
think it is simplistic to assume simple replacement of coag-
ulation factors accounts for the improvement in survival.
Unfortunately, most of the animal models that we have used
are fairly artificial, using lactated ringers, heparin, coumadin,
or hypothermia to generate a coagulopathic state. There is no
trauma and coagulopathy preclinical animal model I am
aware of where shock induces the coagulopathic sate, which
is what we are trying to treat.
To answer several of your questions, we have no data
on the rate of infusion of any products or changes in labora-
tory values over the first 6 hours. This is one of the problems
with performing a retrospective study. We just do not know
what happened during the first 3 critical hours. We have
always said that all bleeding stops one way or the other, and
now we know that that time frame is 3 hours. Unfortunately,
our first time point was 6 hours, so we do not know what
happened in the mixture of those ratios in the first several
hours. However, very few studies have even looked at the
first 6 hours after admission, and based on these data we hope
to accomplish a closer inspection of the first 1 to 3 hours in
a prospective observation transfusion trial that should start
within the next year.
There were no obvious differences between blunt ver-
sus penetrating patients, although this will be the focus of a
future investigation. Recombinant factor VII-A was given in
about 17% of these massive transfusions and there was no
difference associated with survival.
Several of your questions and comments are thought
provoking, but as you know cannot be answered based on
these data. They will be important questions to address in any
prospective trial, which we must do. Amazingly, there are no
prospective randomized data in massively transfused patients.
These retrospective data will hopefully provide the informa-
tion within which to intelligently design prospective trials in
the massively transfused population. We must do this study
as these patients are the ones most likely to benefit, and I
think that we need to understand how best to use and not use
blood products.
I think the point-of-care testing in the ED is an ex-
tremely important and largely overlooked issue. The current
coagulation tests we use are relatively insensitive, and others,
such as the TEG will allow earlier appreciation of more subtle
coagulation abnormalities. With modern machines you can
obtain coagulation results in the ED in 2 minutes, and a
preliminary TEG in 10. They give you much more informa-
tion about what is happening in terms of coagulopathy in your
patient. We now know that a quarter of the patients arrive
coagulopathic within 30 minutes of injury in the emergency
department and we need to focus on that issue just as we have
done with hypothermia and coagulopathy. There is absolutely
no reason not to know the coagulation status of your patient
within minutes of their arrival.
Dr. Trunkey asked about 1:1:1 being reconstituted whole
blood. It is actually worse than that. When you take whole blood
and separate it into components, put it through the machines,
then put it back together, a 1:1:1 ratio is actually an anemic,
thrombocytopenic, and coagulopathic fluid. It does not function
and whole blood when you take it out of the body, although that
is the best you can do. If you add any crystalloid or colloid to the
1:1:1 solution you further dilute the blood products and exacer-
bate the coagulopathy in trauma. Although 1:1:1 is good, I
actually think whole blood is better. Although we are aware of
the issue, based on the labor required we did not calculate the
age of blood in this study.
In response to Dr. Champion, the significant variation
in survival (41%-71%) between centers was enlightening to
me and many of my collaborators. I was assured that with
sophisticated statistics the significant center effects can be
accounted for, but I am not sure I am convinced. I do think
these data can be used to facilitate the discussions on the need
Annals of Surgery • Volume 248, Number 3, September 2008 Blood Component Ratios in Civilian Trauma Patients
© 2008 Lippincott Williams & Wilkins
Page 12
for data driven clinical practice guidelines, especially con-
cerning use of blood products. Rapid delivery of these blood
products can be achieved. About half of the participating
centers put thawed plasma in their ED so that plasma is
available within minutes of the patient's arrival. The thawed
plasma is being used as the primary resuscitation fluid in the
small group of patients that present as acidotic and coagulo-
pathic. This practice requires a lot of coordination between
the emergency department, blood bank, surgery, anesthesia,
and nurses, but it can be done.
Dr. Meyer, your question about the actual timing of
infusions is very good and I think I answered it. With the
current data we just do not know. Dr. Gonzalez and his
group in Houston did address this in their recent Western
Trauma presentation. Their final 24-hour ratios were al-
ways 1:1; however, their 6-hour ratios were closer to 1:2.
Two years ago they started resuscitating their patients with
1:1 with the first unit of RBCs and improved their 6-hour
ratio from 1:2 to 1:1, with an improvement in survival
from 30%-15%.
Holcomb et al
Annals of Surgery • Volume 248, Number 3, September 2008
© 2008 Lippincott Williams & Wilkins


text:
Jay Sekulow & ACLJ Say Iran Sentences American Pastor To Jail Because He Is Christian
Washington DC based, The American Center for Law and Justice (ACLJ), which focuses on constitutional and human rights law said the action by an Iranian court convicting and sentencing American Pastor Saeed Abedini for his Christian faith is a travesty that sadly underscores Iran's brazen violation of international law. In an unexpected development in Iran Judge Pir-Abassi of Branch 26 of the Iranian Revolutionary Court verbally convicted and sentenced Pastor Saeed to eight years in prison for threatening the national security of Iran through his leadership in Christian house churches.
"This is a real travesty — a mockery of justice," said Jordan Sekulow, Executive Director of the ACLJ, who represents Pastor Saeed's wife and children living in the U.S. "From the very beginning, Iranian authorities have lied about all aspects of this case, even releasing rumors of his expected release. Iran has not only abused its own laws, it has trampled on the fundamentals of human rights. We call on the citizens of the world to rise up in protest. We call on governments around the world to stand and defend Pastor Saeed."
Pastor Saeed and his attorney were permitted to attend just one day of his trial, which began January 21st. They were barred from attending and participating in further proceedings. During his imprisonment, Pastor Saeed has been beaten and tortured raising serious concerns about his medical condition.
"The promise of his release was a lie," said Pastor Saeed's wife, Naghmeh:"We should not trust the empty words or promises put out by the Iranian government. These false hopes amount to psychological torture. You don't want to trust them, but they build a glimmer of hope before the crushing blow. With today's development I am devastated for my husband and my family. We must now pursue every effort, turn every rock, and not stop until Saeed is safely on American soil."
ACLJ Executive Director Jordan Sekulow added:
"Here's the troubling reality: we have a U.S. citizen, who has been beaten and tortured since his imprisonment last fall, is now facing eight years in Evin Prison, one of the most brutal prisons in Iran. A harsh sentence in a notorious prison — likely facing life-threatening torture and abuse at the hands of the Iranian regime. Simply because of his Christian faith."
The ACLJ is providing legal representation to his U.S.-based family and working with various contacts in Iran on his case. Led by Chief Counsel: Jay Sekulow, the American Center for Law and Justice is headquartered in Washington, D.C. and has affiliated offices in Israel, Russia, Kenya, France, Pakistan, and Zimbabwe.
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subset: commoncrawl


text:
Men's Hockey Set For Weekend Home-And-Home Series Vs. UMass
The Friars' final regular-season home game will be on Friday night.
No. 9 Men's Hockey Hosts No. 20 Notre Dame For Weekend Series
The Friars and Irish will meet for the first time as Hockey East opponents.
No. 7 Men's Hockey To Host No. 2 Boston College
The Friars and Eagles close out their regular-season series on Friday night at Schneider Arena.
Men's Hockey Continues League Play Versus Merrimack
The No. 5/6 Friars are at home on Saturday night against the Warriors.
Top-10 Showdown At Schneider As No. 8 Men's Hockey Hosts No. 3 Miami
The two-game series begina at 5:20 p.m. on Friday, Oct. 25
One of the top goaltenders to ever play at Providence College, the 2011-12 season marked Bob Bellemore's 19th season as an assistant coach with the women's hockey team. In addition to working with the goaltenders, he assisted with scouting and other various duties. He is also involved with the USA hockey elite training camps that take place in Lake Placid, N.Y. Coach Bellemore helps lead the goaltending segment of the camp.
As a sophomore in 1964, he helped the Friars win their first ECAC title and earn their first berth in the NCAA Final Four. Bellemore also starred on the school's baseball team and served as the team's captain his senior year. In 1984, he was inducted into the Providence College Athletic Hall of Fame.
Bellemore began coaching as a part-time assistant for PC's men's hockey team. In 1972, he joined head coach Lou Lamoriello's staff as a full-time assistant - a position he held until 1986. In 1986-87, Bellemore held the title of Arena Director and was in charge of the day-to-day operations of Schneider Arena. Bellemore left Providence College in 1987 to serve as the goaltender coach for the New Jersey Devils. In 1991, he left New Jersey to pursue his master's degree at PC. Since earning his master's degree in special education, Bellemore has been employed as a special education instructor at South Kingston High School. He now serves as a guidance counselor at South Kingston High.
A native of Smithfield, R.I., Bellemore resides in Westerly, R.I., with his wife Marguerite. He has one son, Bruce, a 1991 graduate of PC, who played hockey for two seasons for the Friars. He also is the proud grandfather of nine. Bruce and his wife Eileen, who also graduated from Providence, have triplets, Brendan, Jolie and Laurel and the grandchildren from Marguerite's children include Zachary, Devon, Sofia, Christopher, Alec, Luke, Cole and Sebastian.
Official StoreOfficial Online
Women's Hockey Comeback...
After a two-goal third period to tie the game, the Providence College women's ice hockey team fell to the University of Vermont Catamounts by a score of 3-2,...
Great Promotions to Finish...
The Providence College Athletic Department is excited about some upcoming promotions at Friar home games.
Women's Hockey Closes...
Providence will host Vermont in its final regular season games on Saturday, Feb. 21 and Sunday, Feb. 22. Both games are set to start at 2:00 p.m. at...
Women's Hockey Defeated ...
The Providence College women's ice hockey team was defeated 7-1 by No. 7 Boston University on Monday night at Walter Brown Arena. With the loss the Friars...
Women's Hockey Falls 6-1...
The Providence College women's ice hockey team dropped a 6-1 decision to the No. 7 Boston University Terriers on Saturday Feb. 14 at Schneider Arena. The...
Women's Hockey Game On...
The Providence College women's hockey game at No. 7 Boston University, originally scheduled for Sunday (Feb. 15) at 2 p.m., has been moved to Monday (Feb. 16...
Women's Hockey Competes In...
Providence play home-and-home contests against No. 7 Boston University on Saturday, Feb. 14 and Sunday, Feb. 15. Saturday's game will start at 2:00 p.m. at...
Women's Hockey Falls 2-1...
The Providence College women's ice hockey team was defeated by Northeastern, 2-1, in overtime on Friday night at Matthews Arena. Northeastern used a third...


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People love our work ethic and customer service.
This guy (Bruce Angeloszek) and his service is worth his weight in gold. For his quoted price, he got all the permits necessary to hook up our new, whole-home emergency generator from our town, added the equipment, wires and initially, battery necessary to make sure it ran, and now maintains it. I've always gotten a call back- from him- within a short time that I call the service. He explained everything to me that I needed to know, including how to become better informed about this specific kind of generator online. He even placed stickers for any maintenance/services people so they know that we have one and where it is placed in back of the house. We 'tested' it when we lost power early this winter after a tree fell on our electric power line to the house, and it went on like a charm. It's great to hear it self-test every week- and to know our electrician is as reliable as our Generac generator!
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Federal Court orders Walton Construction liquidator removal in ASIC win
PUBLISHED: 18 Jul 2014 12:08:00 | UPDATED: 20 Jul 2014 17:08:12PUBLISHED: 18 Jul 2014 PRINT EDITION: 19 Jul 2014The full bench of the Federal Court on Friday has backed the Australian Securities and Investments Commission and ordered the removal of Walton Construction's liquidators.
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Cabarrus Arts Council Galleries www.cabarrusartscouncil.org OnlineWebsite - www.cabarrusartscouncil.orgSend an email - email@example.com & SeasonsSeasons - Year-RoundHours - Regular gallery hours are 10 a.m.-4 p.m., Monday - FridayAddressHistoric Courthouse, 65 Union Street SouthConcord, NC 28026PhonePrimary - (704) 920-2787 The Arts Council Galleries, which include the Judge Adam Crawford Grant, Jr., Gallery and the Martha Hughes Dusch Gallery are located in the renovated Historic Cabarrus Courthouse at 65 Union Street in Downtown Concord. The majestic building, which was built in 1876 and is on the National Register of Historic Places, also houses offices for the Cabarrus Arts Council and Historic Cabarrus. A theatre for professional performances will open in 2008 in the former courtroom upstairs. The galleries, which are operated by the Cabarrus Arts Council, feature nationally and regionally prominent artists working in a variety of media. In addition, one gallery displays work by local artists of merit. Gallery talks by artists and other special events are held regularly. A gallery shop sells unique handcrafted items ranging from pottery to jewelry to textiles. Trained volunteer docents are available for tours of the galleries and the historic building. Admission is free. For information or to arrange a tour, call 704-920-ARTS (2787). AmenitiesHandicap accessibleTours – guidedTours – self-guided
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text:
Great sex does more than blow your mind—it's good for your heart, your head and your beauty.
I'm sure many of you will have, at some point in your lives, been admonished "not to judge a book by its cover."
This old idiom advises us that we shouldn't judge or treat others differently based on their appearance alone. Coupled with that other saying—"beauty is but skin deep"—age-old wisdom would seem to suggest that a person's physical appearance is rather trivial and doesn't reflect their real, inner qualities.
What about you? Have you ever judged a book by its cover?
Let me put the question to you a little differently: Do you think you make different judgments about attractive and less attractive people? Chances are, you probably do, even if you wouldn't want to admit it! Decades of psychological research have shown that a person's physical appearance can have a huge impact on how they're perceived and treated by others.
QUIZ: How Satisfied Are You With Your Face?
"What is Beautiful is Good"
Consider this classic study by Elaine Walster and her colleagues. College students were invited to a dance and, when they arrived to pick up their tickets, the researchers secretly rated each participant's attractiveness. The students then completed a survey about their personality, intelligence, and personal information, and were later randomly paired up with another participant, who would be their date for the dance. Halfway through the dance, the students completed another survey about their dates and how interested they were in a second date.
So, what do you think affected the romantic attraction these participants felt toward their date? Their date's intelligence or personality? Or the degree to which the pairs shared common interests? It turns out, the only predictor of romantic interest was how attractive the date was, regardless of participants' own attractiveness. Participants who'd been paired up with attractive dates were more likely to show an interest in their partner, want to go on a second date, and even more likely to actually ask their date out.
This classic study shows just how important physical attractiveness can be in our everyday lives. In fact, many studies have shown that we make judgments about others based solely on their appearance.
We judge books by their covers.
In another classic study, Ellen Berscheid and her colleagues asked participants to view photos of a physically attractive person and a physically unattractive person. The participants then rated the people they saw in the photos along a number of different dimensions.
What the researchers found was that participants made all kinds of positive attributions of the attractive person, based solely on the photographs they saw. For example, they judged the attractive person as being more interesting and having more a desirable personality. They even judged the attractive person as being more likely to get a prestigious job, to have a happier marriage, and to lead a happier life in general.
This study is often said to demonstrate a 'what is beautiful is good' bias. In our perceptions of other people, we tend to think that attractive people are 'good' along all kinds of dimensions. In fact, other studies have suggested that we judge attractive people as being more honest, less maladjusted, more sociable and popular, and generally better at everything they do!
So much for beauty being skin deep. Whether we do it consciously or not, the evidence suggests that we assume a person's physical attractiveness reflects their inner qualities.
MORE: Is Your Mate Hotter Than You?
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My baby wants to be held all the time. Help!
My 2-month-old will only stay quiet for a few minutes after I put her down -- then she starts crying. I try everything to settle her down, but she won't stop crying until someone picks her up again. I feel like my arms are about to fall off. What can I do?
Posted: 10/13/2004 by a BabyCenter Member
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MY SON IS 2 MONTH OLD MY WIDE STILL WOMEN THINK SHE GET EVERY MOTHposted 11/12/2007 by wolframjim
MY SON IS 2 MONTH OLD MY WIDE STILL WOMEN THINK SHE GET EVERY MOTHposted 11/12/2007 by wolframjim
my baby is 3 weeks old and has benn fussy for 2 days we are not getting any sleep i've tried everything swing bouncy seat walks car rides nothing will settle him down what should i do?posted 05/31/2007 by a BabyCenter Member
My 8 month old is always cranky...nothing seems to help. He wants to be held and if he doesnt get what he wants he screams until he gets it. What should I do???posted 05/25/2007 by a BabyCenter Member
My baby is 4 weeks old and cries when ever I put him down. This includes sleeping. He fights his sleep. I can lay him down and he wakes up ever time within 10 minutes or less. I can't seem to get a break. He wont sleep anywhere but with me. I'm really at a loss at what to do. He is sleeping in our bed because I can't get any sleep otherwise. I tried letting him cry it out but after an hour we couldn't take it anymore. I don't know what to do? How do I get him to sleep on his own or even be content in his bouncy chair or swing?posted 04/21/2007 by jsauls
my daughter had to be held all the time and wanted attn. too i couldnt even take a shower unless my husband was home she only took cat naps during the day between 10 - sometimes 20 min i no sooner started to clean the house and she would wake up and cry and i would have to pick her up also i couldnt sit down id have to hold her standing up my back hurt soooo bad i was so tired they say sleep when the baby sleeps but how can you when they only take short naps by the time i fell asleep she would wake up and cry i had a hard time falling asleep because i kept thinking i should be cleaning my house or do something else i needed to get done. so one day i sat on the couch with her put my feet up on the table and fell asleep with her in my arms and she slept for more than an hour and thats the only way i can get her to take long naps i also found what worked for a while and still does sometimes is going for a ride in the car when i get back i leave her in the car seat all bundled up and i got a few hours to myself one day she was so tired and screamin her head off that i bundeld her up put her in the car seat like we were going to go for a ride within 5 mins she fell asleep the first few months she wasnt happy unless i was holding her sometimes holding her doesnt help either then when she was 4 months old i could find some ways to entertain her at first not for long but eventually for longer periods of time she slept thru the night since about 3-4months but since we switched her to the crib she wakes up several times during the night and crys then ill comfort her and she goes back to sleep but she seems uncomfortable in the bigger bed she is now 6months old and starting to want to get held alot again i guess it must be phases babys go thru and it leaves you constantly guessing on what she wants/needs its frustrating that they cant tell you whats wrong any ways if any has any suggestions on how to make her more comfortable sleeping in her crib id really appreciate it. good luck/stay calmposted 03/29/2007 by joyce0517
My 4month old got frightened by a loud noise today and cried like never before. Now he's all jumpy and has little crying fits. What should I do? Please help.!!!posted 03/23/2007 by cindyyr81
And also.... don't feel bad, or let anyone MAKE you feel bad, for wanting a break from holding your baby. We're only human, and it can get tiring, especially when you've been CARRYING them for the last 9 months. You feel that natural need for a little space, to go to the bathroom or grab a bite to eat while baby sleeps... If you feel like holding your baby constantly, good for you... but don't feel bad if you want to take a little break. There's nothing wrong with that and it DOENS'T change the love you have for your child.posted 12/13/2006 by tamaranne522
I do have the same dilema. Plus the fact that my baby also wants humming while being swayed to sleep.. Think of it this way, your baby is only 2 months and simply looks for mommy. The smell and mommy's hug. Not to mention the bonding there. :-)posted 12/10/2006 by a BabyCenter Member
Hi Michelle, We have and are still experiencing the same problem but not as much as before. Our first challenge was the fact that our son was born at 33 wks and only weighing 3lbs 4 oz. The special care nursery staff and doctors told us that our son would require more hands on attention considering he was early and may experience seperation anxiety. Now at 4 months he is really starting to show some signs of independance.His calming vibrations chair and swing, along with a couple favorite blankets have saved us ALOT of frustrations. Personally my advice is if you find something( anything-toy, swing, blanket) that seems to keep his attention, work with that and routine, routine, ROUTINE!... only after we reallly sacrificed alot of our time and stayed focused on our bedtime routine does he not need to be held all night. Keep in mind that just like we long to be held and touched my our partner or enjoy a hug or kiss from a family/friend your baby will at times need that from you! And sometimes for long periods of time. We also have experienced the same issues with acide reflux. The advice our Dr gave was try and feed ( if bottle fed) your baby sitting up more. ALWAYS have a half way burp and keep your baby upright for about 20 mins after feeding. It's worked for us. I must also agree with previous comments that no matter how much expert or other advice you get from other mothers, do what YOU and your partner feel is right!posted 11/26/2006 by a BabyCenter Member
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text:
(cause they scratchin with the) toe
(and even his el)-bow! (HA!)
from Run-D.M.C. (Ft. Yellowman) – Roots, Rap, Reggae Lyrics on Genius
With the evolution of DMC DJ Mixing Championships, several DJs wanted to take the art to another level and thus included controversial body tricks to their sets.
These included scratching and using their hardware with their feet, elbows or any other body part… dancing around the set and many more.
One of the most outrageous and fun these body tricks was this by DJ David (2 times DMC World Champion from Germany):
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