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Review

Whole Blood, Fixed Ratio, or Goal-Directed Blood Component Therapy for the Initial Resuscitation of Severely Hemorrhaging Trauma Patients: A Narrative Review

by
Mark Walsh
1,2,
Ernest E. Moore
3,4,
Hunter B. Moore
4,
Scott Thomas
5,
Hau C. Kwaan
6,
Jacob Speybroeck
1,
Mathew Marsee
1,
Connor M. Bunch
1,
John Stillson
1,
Anthony V. Thomas
1,
Annie Grisoli
1,
John Aversa
7,
Daniel Fulkerson
8,
Stefani Vande Lune
9,
Lucas Sjeklocha
10 and
Quincy K. Tran
10,*
1
Notre Dame Campus, Indiana University School of Medicine, South Bend, IN 46617, USA
2
Departments of Emergency & Internal Medicine, Saint Joseph Regional Medical Center, Mishawaka, IN 46545, USA
3
Ernest E. Moore Shock Trauma Center, Denver Health, Denver, CO 80204, USA
4
Department of Surgery, University of Colorado Health Science Center, Denver, CO 80204, USA
5
Department of Trauma Surgery, Memorial Leighton Trauma Center, Beacon Health System, South Bend, IN 46601, USA
6
Division of Hematology and Oncology, Department of Medicine, Northwestern University Feinberg School of Medicine, Chicago, IL 60611, USA
7
Department of Surgery, Indiana University School of Medicine, Indianapolis, IN 46202, USA
8
Department of Neurosurgery, Beacon Medical Group, South Bend, IN 46601, USA
9
Emergency Medicine Department, Navy Medicine Readiness and Training Command, Portsmouth, VA 23708, USA
10
The R Adams Cowley Shock Trauma Center, University of Maryland School of Medicine, Baltimore, MD 21201, USA
*
Author to whom correspondence should be addressed.
J. Clin. Med. 2021, 10(2), 320; https://doi.org/10.3390/jcm10020320
Submission received: 10 November 2020 / Revised: 15 January 2021 / Accepted: 15 January 2021 / Published: 17 January 2021
(This article belongs to the Special Issue Clinical Management of Major Bleeding and Coagulopathy Following Trauma)
Versions Notes

Abstract

:
This narrative review explores the pathophysiology, geographic variation, and historical developments underlying the selection of fixed ratio versus whole blood resuscitation for hemorrhaging trauma patients. We also detail a physiologically driven and goal-directed alternative to fixed ratio and whole blood, whereby viscoelastic testing guides the administration of blood components and factor concentrates to the severely bleeding trauma patient. The major studies of each resuscitation method are highlighted, and upcoming comparative trials are detailed.

1. Introduction: Rationale for the Adoption of Whole Blood and Fixed Ratio Resuscitation

1.1. History of the United States’ Swift Adoption of Cold-Stored Whole Blood for Civilian Urban Trauma Resuscitation

Since 2016, many large United States academic centers have embarked upon an ambitious program to offer whole blood (WB) in the civilian and urban prehospital environment for severely hemorrhaging patients. This process required variances from the American Association of Blood Banks recommendations [1,2]. In austere and rural environments where no blood banking or testing is available, cold-stored WB (CSWB) may be the best empiric agent for prehospital resuscitation of the severely bleeding patient. Prehospital fresh frozen plasma is commonly available. However, recent studies demonstrate that platelet dysfunction and fibrinogen deficiency are of paramount importance in early trauma-induced coagulopathy (TIC) [1,2,3,4]. Therefore, some urban academic trauma systems with short transport times have been early adopters of CSWB. Many of these academic centers who advocate for trauma resuscitation with WB are led by trauma specialists with military backgrounds [1,2]. In turn, there has been a significant drive to provide CSWB not only in the rural civilian environment—where its use is beneficial given transport times and resource limitations—but also to the urban nonacademic environment with short transport times [1,2,3,4,5,6,7,8,9,10]. Without access to similar robust academic and/or military ties, these nonacademic trauma centers may not have the resources to offer WB as easily as their academic and military counterparts. Therefore, the mechanistic rationale for the provision of CSWB in the civilian and urban environment requires historical evaluation prior to its widespread adoption.

1.2. PROPPR Trial as Mechanistic Rationale for Justification of CSWB

WB resuscitation garnered practical support by the demonstration that a fixed ratio of equal parts plasma, platelets (PLTs), and packed red blood cells (PRBCs) improves mortality. The 2015 Pragmatic, Randomized Optimal Platelet and Plasma Ratios (PROPPR) trial established use of balanced blood transfusion. This study of 680 patients from 12 centers suggested that a fixed ratio of 1:1:1 (plasma/PLTs/PRBC) provided a benefit to mortality caused by exsanguination at 24 h but no overall mortality benefit when compared to a ratio of 1:1:2 [11]. The PROPPR trial has received significant scrutiny because of the lack of benefit in overall 24 h mortality. The trial has also received criticism for inconsistencies and confounding variables. PLTs were not provided to the 1:1:2 group until after 6 units of PRBCs were administered. Moreover, cryoprecipitate or fibrinogen were not components of either regimen. Plasma was often administered well after the initial resuscitation period but within the first 24 h. This phenomenon was termed “catch up” and implied that these patients did not receive equal components during the critical first few hours of resuscitation. Therefore, patients never truly received a fixed 1:1:1 ratio during the initial resuscitation period. Finally, patients whose cause of death was exsanguination included those who also had traumatic brain injury (TBI), which confounded the cause of death [11,12,13,14]. A follow-up systematic review of 16 randomized controlled trials (RCTs) stated similar concerns regarding the recommendations of the PROPPR trial. Given the diversity of patients with blunt or penetrating trauma and with or without TBI, additional studies are required to determine the mortality benefit of 1:1:1 vs. 1:1:2 fixed ratios [12,15,16]. Due to the concerns about the validity of the PROPPR trial, which set the standard for the fixed 1:1:1 practice, we review the reasons for the widespread adoption of CSWB in the United States for civilian urban trauma.

1.3. Historical Justification for CSWB in Civilian Urban Trauma

Few retrospective studies and only one RCT compared WB versus fixed ratio for resuscitation in the urban civilian population (Table 1). The first study comparing WB versus standard blood component therapy (BCT) for civilian resuscitation was published in 2009. Since then, the paucity of literature mostly constitutes editorials or papers on the feasibility of applying far forward combat WB use to the civilian arena. A total of 1382 civilian patients form the foundation of WB’s widespread adoption in the United States’ urban areas [1,2,3,4,5,6,17,18,19,20,21,22,23,24,25,26,27,28,29,30,31,32,33,34,35,36,37,38]. The most recent small studies revealed an equivocal mortality benefit from overuse of WB because “it was easier and faster in a chaotic and busy trauma bay” [29]. Moreover, it was recently noted that “WB is not effective at treating traumatic hemorrhage in resuscitation as compared with component therapy” [33]. Broad introduction of CSWB in the absence of high-quality trials will likely lead to further heterogeneity of guidelines among hospital systems and education programs. Three RCTs, discussed later, are currently underway and the results will not be reported for over a year. Given the scant literature justifying CSWB in the prehospital and urban environment for trauma, and the concerns regarding the PROPPR trial, consideration of viscoelastic test (VET)-guided trauma resuscitation is warranted.

2. VET-Guided Goal-Directed Resuscitation

The rationale of CSWB and fixed ratios is based on the principle that the patient should be “given what they have lost” [39]. There are significant temporal changes within the complex spectrum of TIC within the first hours of resuscitation [40]. The complex pathophysiology of TIC often persists after the simple administration of fixed ratios or WB, and TIC remains a leading cause of mortality after resuscitation. TIC phenotypes, an intricate web of hemostatic and immunologic aberrancies, depend on factors such as penetrating versus blunt trauma, the presence of TBI, the time from injury to resuscitation, the genetic hematologic makeup of the patient, and the methods of resuscitation. The administration of either fixed ratios or WB does not represent a precision-based therapeutic approach to the individual patient’s hemostatic derangements in TIC, especially when guided only by common coagulations tests such as the prothrombin time, international normalized ratio, activated partial thromboplastin time, PLT count, and fibrinogen. As a result, there has been advocacy for administration of BCT under the guidance of the VETs, including thromboelastography (TEG) and rotational thromboelastometry (ROTEM) [41,42,43,44,45,46,47,48,49,50,51,52,53,54,55,56]. This strategy of VET-guided goal-directed BCT (GD BCT) can be considered a better alternative for individualized resuscitation of the hemorrhaging trauma patient.

2.1. History of VET and Trauma Resuscitation

In 1997, the first case series of 67 trauma patients whose BCT was guided by TEG was published in the United States [57]. Since then, numerous papers in worldwide journals have detailed how TEG/ROTEM provides more efficient resuscitation of severe bleeding in not only trauma, but also surgical anesthesia and obstetrics [42,58,59,60]. However, the adoption of the TEG/ROTEM in the United States has remained stagnant. In 2016, it was discovered that only 9% of institutions used VET-guided BCT for patients who required large volume resuscitation [61,62]. Meanwhile, our European colleagues have adopted early and repeated VET-guided BCT as the bedrock of modern trauma resuscitation. Since the beginning of the century, European guidelines and their iterations have recommended VET-guided BCT for initial and ongoing resuscitation of the severely bleeding trauma patient [63,64,65]. Despite this significant history in Europe, VET-guided BCT has failed to gain acceptance in the United States where continued emphasis on common coagulations tests guide therapy. This may be explained in part by the inherent bias of blood bankers and hematologists who often lack familiarity with TEG/ROTEM due to institutional variability caused often by pipetting inconsistencies [66,67]. Standardization of VETs is being addressed with controlled cartridge systems, such as the TEG6S and ROTEM Sigma. These enable easier implementation of rapid test variants of VET assays and decreased time to potentially actionable information [68,69,70,71].
Initial trauma resuscitation in the United States may be led by either a trauma surgeon and anesthesiologist, or an emergency physician. There has been a recent push in the United States to approach trauma care with more attention to the pathophysiology of TIC. Thus, it is vital that acute care trauma surgeons and critical care surgeons are provided the educational impetus to advance the use of the VETs seamlessly throughout the hospital. Whether in Europe or the United States, a seamless transitioning of TIC prevention and management—guided by TEG/ROTEM—has resulted in a more physiologic replenishment of blood products in the trauma patient [68,69,70,72,73].
Since 2012, Germany has undergone concerted educational and institutional efforts to use VETs to guide trauma resuscitation in a more physiologic manner. At the beginning of the century, the multicenter trauma registry of the German Society for Trauma analyzed ratios of plasma, PRBCs, and PLTs and administration of coagulation factor concentrates (CFCs) in adult trauma. As a result, a significant reduction in crystalloid use and a higher ratio of plasma and PLTs to PRBC use, as well as an increase in CFCs, were noted to improve mortality in the studied time frame. Most recently, the findings of the German study group have advanced many areas of VET-guided BCT and hemostatic adjunct therapy with 4-factor prothrombin complex concentrate (PCC) and soluble fibrinogen [47,74].
A Copenhagen group used a hybrid approach of an initial 1:1:1 fixed ratio followed by TEG-guided GD BCT with factor concentrates. This landmark study published in 2010 establishes the “Copenhagen Concept”, which has become a standard for the treatment of hemorrhaging trauma patients [54,75]. Likewise, an Italian group using ROTEM-guided therapy has demonstrated a similar protocol wherein a preemptive dose of 2 g fibrinogen concentrate is administered for trauma patients in hemorrhagic shock. The Italian group demonstrated reduced blood product consumption, decreased overall cost, and improved early and 28 day mortality [76].

2.2. History of VET Goal-Directed Therapy with Coagulation Factor Concentrate

Personalized VET-guided direction of BCT possesses theoretical advantages over the WB and ratio-driven methods. Despite the increasing availability of rapidly obtainable VET results, which allow for the targeted supplementation of procoagulants, consensus among physicians regarding the use of factor concentrates is lacking, particularly in the United States. Prospective studies and RCTs comparing GD BCT with and without CFCs are necessary
Not all blood components are depleted equally in hemorrhage. Resuscitation itself causes the dilution of the coagulation process and factors. There has been renewed interest for the use of VET-guided fibrinogen administration in Europe and the United States. Fibrinogen is the precursor for clot formation and its level determines the clot stability early in resuscitation. Early prehospital and emergency department fibrinogen for preventing the progression of TIC has been a significant area of recent study. Attention has also been brought to early hospital use of PLT therapy in order to enhance the stability of the fibrin/PLT plug as studies have shown that higher ratios of PLTs provided early to patients with surgical and traumatic bleeding are associated with increased survival [77,78,79,80,81,82,83,84].
European studies reveal that cryoprecipitate replacement for fibrinogen levels greater than 1–5 g/L was feasible in patients who required massive transfusion (MT). Studies have demonstrated the feasibility of providing fibrinogen concentrate to severely bleeding trauma patients. The Fibrinogen in the initial Resuscitation of Severe Trauma (FiiRST), REversal of Trauma-Induced Coagulopathy (RETIC), and Early-Fibrinogen In Trauma 1 (E-FIT1) studies, as well as the European prehospital Fibrinogen in Trauma-Induced Coagulopathy (FinTIC) trial, have demonstrated that soluble fibrinogen given early during trauma resuscitation may result in significant clinical benefit. The RETIC study used plasma in the control arm to treat early TIC and compared it to soluble fibrinogen in patients in whom ROTEM indicated a fibrinogen deficiency. The study was terminated early because a significant number in the plasma group required rescue therapy and MT compared to the CFC group. Soluble fibrinogen is costly while cryoprecipitate is less expensive and more readily available. The CRYOSTAT1 and two trials are designed to study the efficacy of cryoprecipitate for the maintenance of resuscitation for fibrinogen levels greater than 1.8 g/L. These trials advocate for the early administration of cryoprecipitate in the prevention and treatment of early TIC because of the early fibrinogen derangement as a cause of incipient TIC. Recent studies indicate that timely soluble fibrinogen concentrate administration is possible in the prehospital and urban hospital environment, with ROTEM evidence of increased clot stability. Future studies have been proposed to provide soluble fibrinogen and 4-factor PCC in the prehospital and hospital civilian urban setting as an alternative to fixed ratio or WB resuscitation [85,86,87,88,89,90,91,92,93,94,95,96]. Since 2017 in Australia, the Fibrinogen Early In Severe Trauma study (FEISTY) is a RCT attempting to address the validity of soluble fibrinogen for early resuscitation of severely bleeding trauma patients [97].
With precision-based medicine guided by VETs, the hemorrhaging trauma patient’s resuscitation is provided by a finely-tuned menu to address their individual hemostatic deficits. TEG/ROTEM-guided therapies represent an area of promise mastered by more than a few European centers, but lags in the United States where CFCs are not yet approved for trauma resuscitation [98].

2.3. Recent Challenge to VET-Guided Trauma Resuscitation: The iTACTIC Trial

A recent RCT has challenged the value of VET-guided BCT and CFC in severely bleeding patients. The implementing Treatment Algorithms for the Correction of Trauma-Induced Coagulopathy (iTACTIC) trial compared VETs to the standard coagulation tests in bleeding trauma patients. This trial demonstrated no statistical evidence that the use of VETs versus standard therapy guided by standard coagulation tests improved 28 day mortality. However, similar confounding factors were also found with the PROPPR trial [99]. Despite the high injury severity scores, a relatively small percentage of either group received MT within 24 h. This is also reflected by the low incidence of TIC in both groups. Like the PROPPR trial, no proportion of patients were identified with significant surgical bleeding. Moreover, there was a confluence of those patients with TBI and hemorrhagic death, rendering any causal link of death to hemorrhage problematic. While some of the centers in the iTACTIC trial had been performing TEG and ROTEM at a clinical level for many years, other centers began their practical experience with VETs at the beginning of the study. The authors of the iTACTIC study note the challenges in attempted performance homogeneity among the seven centers. This raises significant concern for the validity of the results, as there is a steep learning curve in the adoption of VETs to guide BCT and CFCs for severely bleeding patients. Additionally, the authors of the trial do not comment on the percentage of centers which used either ROTEM or TEG devices to guide BCT. They state: “The [VET] used at each study site was determined by existing familiarity with a specific device appliance and to ensure a balanced use of the devices across the study” [99]. This is of importance due to the heterogeneity of thresholds for administering BCT [100,101]. Finally, a problem consistent with many studies regarding the treatment and diagnosis of patients with severe bleeding and trauma is the definition of MT as 10 units PRBCs in 24 h. This may explain the low incidence of TIC in the iTACTIC study considering that the most effective time for intervention to reverse the pathophysiology of TIC is the first few hours after injury. Only 28% in the standard coagulation tests group and 26% in the VET group had received MT at 24 h [99]. This traditional MT definition restricts the potential study sample to a less acute group of patients, excludes patients who die early, and excludes those who may have benefitted from early use of VET-guided resuscitation [102]. These issues indicate that the population studied may not have been sick enough to benefit from VET-guided trauma resuscitation [99]. More recent data suggest that >4 units PRBCs in the first hour is a more meaningful definition of MT [103].

3. Geographic Variations

Comparison of the United States and European trauma data is confounded by the relatively high incidence of penetrating injury in the United States. The United States’ emphasis on WB may stem from this high incidence of penetrating injury as an early cause of potentially preventable hemorrhage (PPH), serving as an impetus to provide WB in the civilian urban environment. It has been reported that 34.5% of patients died from PPH in the prehospital setting or within an hour of hospitalization for all forms of trauma. Hence, the use of WB in the early prehospital and emergency department environment has been viewed as a more effective method for prehospital resuscitation to decrease deaths from PPH [104].
The incidence of penetrating injury varies among developed countries. In major United States trauma centers in large metropolitan areas, the incidence may be as high as 45% of all injuries, whereas in Europe the percentage of penetrating injuries is much lower (0.2–5% in Switzerland, the Netherlands, and Germany) [105,106].
Resuscitation of these penetrating injuries also depends on immediate surgical control of hemostasis. Therefore, this population may not be directly comparable to the European population, where motor vehicle accidents with a high incidence of TBI confer different methodologies of resuscitation. Nevertheless, it is notable that the country with the highest use of VETs also has the least use of prehospital blood products administered in a fixed ratio. Germany, with its centralized system and relatively short transport times, uses prehospital blood products in 6% of trauma centers. Comparatively in France, the rate is 89% [16]. It is not surprising that the only European RCT for using CSWB in the civilian urban population is in France, where the time spent in the field on resuscitation efforts is longer than the “scoop and run” strategy used in the United States, where physicians are not onboard ambulances [107].
The equivocal success of prehospital administration of blood products in the civilian urban environment has been inconsistently replicated in other studies. A recent review of the European literature suggests that prehospital blood transfusion with or without PRBCs resulted in equivocal reduction of 24 h mortality [15,85,108]. The authors caution that “based on mainly poor-quality evidence, no hard conclusion can be drawn about a possible survival benefit for hemorrhagic trauma patients receiving prehospital blood transfusion. Overall, prehospital blood transfusion is safe, but the results of currently ongoing RCTs await to demonstrate a survival benefit.” [15]. However, the European Society of Anesthesiology recently reported that 48% of responders to an online survey had access to PRBCs, 22% to fresh plasma, and 14% to lyophilized plasma [16]. It is clear that there were significant dissimilarities in practice among European countries with no consensus regarding the benefit of prehospital blood products [16]. Hence, there is a tremendous need for continued investigation in RCTs.
On the other hand, European trauma specialists have provided substantial literature confirming the use of VETs to guide resuscitation in the last two decades. An expanding emphasis for use of VET-guided BCT in trauma resuscitation has developed throughout Europe and the United States [40,42,44,46,47,54,55,90,94,109,110,111,112,113,114,115,116,117,118,119,120,121].
The most significant difference between Europe and the United States concerns the frequent use of VET-guided administration of PCC, soluble fibrinogen, PRBCs, and PLTs. The European reliance on VET-guided resuscitation and CFC therapy is significant; 2019 guidelines no longer recommend the use of plasma for the treatment of hypofibrinogenemia.
The European guidelines are significant in that fibrinogen and PLT dysfunction are addressed among the first abnormalities in patients with TIC. The volume of plasma required to correct this fibrin deficiency, documented by ROTEM, would result in unnecessary dilution and potential worsening of the coagulopathy. The RETIC study demonstrated the superiority of CFC when compared to plasma [78,79,80,81,82,83,84]. Highly specialized trauma centers in Switzerland, Austria, and Germany have published studies demonstrating mortality improvement for patients with severe trauma who are treated in a goal-directed fashion with CFCs and minimal crystalloid [78,85,87,94,111,118,122,123].
VET-guided GD BCT has now been used in the United States and Europe with increasing frequency and earlier in the phases of care. From our literature search, there was no evidence of VET use in the prehospital environment. VETs are not useful in the prehospital setting because vibrations in a moving ambulance result in an inaccurate tracing.

4. Future Direction—RCTs in Progress

There are three ongoing trials for early trauma resuscitation with WB for severely bleeding patients, the PPOWER trial, the STORHM trial, and the SWAT trial.

4.1. PPOWER

The Pragmatic, Prehospital, Type O, Whole Blood Early Resuscitation (PPOWER) trial, a single-center, 3 year, prospective randomized pilot trial of type O low-titer, leukocyte-reduced (LTLR) WB, is in progress at Pittsburgh, United States. This trial is based in the helicopter prehospital setting followed by LTLR WB in the hospital. Four helicopter centers are provided with WB for this study. Patients will receive 6 units of WB upon entry into the study. Of note, previous protocols called for 2 units of WB, then transitioned to TEG-guided GD BCT. This study provides a higher number of WB units followed by TEG-guided resuscitation, rendering this a hybrid study combining the use of WB, fixed ratios, and TEG-guided GD BCT. The hypothesis of this study is that WB will provide better outcomes for the early resuscitation of trauma patients, particularly when combined with TEG-guided BCT. Proposed completion is by late 2021 [124].

4.2. STORHM

A French study (Sang Total pour la Reanimation des Hemorragies Massives, STORHM) is still in the planning stage as a noninferiority study to compare LTLR WB to a 1:1:1 fixed ratio for the severely hemorrhaging trauma patient. Like the PPOWER study, the endpoint will be mortality, but TEG parameters will also be analyzed. Other endpoints are to include lactate clearance and the presence of multiorgan failure at 24 h. It is anticipated that this trial, which began in late 2019, will recruit 200 patients from six trauma centers [125].

4.3. SWAT

Finally, the Linking Investigations in Trauma and Emergency Services network—a consortium of trauma centers that conduct prospective, multicenter, injury care, and outcomes research—has sponsored the Shock, Whole Blood, and Assessment of TBI (SWAT) trial to compare WB and standard BCT. This trial is a 4 year, multicenter, prospective, observational cohort study that will analyze early WB resuscitation compared to standard BCT resuscitation for trauma patients with severe hemorrhagic shock, with and without TBI. Completion is scheduled for February 2022 [9].

5. Conclusion

Historical, geographical, and mechanistic components influence the selection of fixed ratio blood component and WB resuscitation for severely bleeding trauma patients. Because of an institutional reliance in the United States, based on the paradigm of far forward combat resuscitation where WB is commonly used, a rapid implementation of WB in the civilian urban resuscitation has occurred. In much of Europe, however, with a long tradition of VET-guided trauma resuscitation, fixed ratio resuscitation is less commonly used and WB is only used in the initial stages of investigation. Until recently, few academic trauma centers in the United States have used VETs to guide trauma resuscitation, rather adhering to fixed ratios or CSWB. The advantages and disadvantages of the three resuscitation methods are summarized in Table 2.

Author Contributions

Conceptualization: M.W., E.M., H.M., S.T., H.C.K., J.S. (Jacob Speybroeck), M.M., C.M.B.; Methodology: M.W., E.M., H.M., H.C.K., J.S. (Jacob Speybroeck); Formal analysis: M.W., J.S. (John Stillson), A.V.T., A.G., J.A., D.F., S.V.L., L.S., Q.K.T.; Investigation: M.W., J.S. (John Stillson), A.V.T., A.G., J.A., D.F., S.V.L., L.S., Q.K.T.; Data curation: C.M.B., J.S. (John Stillson), A.V.T., A.G., J.A., D.F., S.V.L., L.S., Q.K.T.; Writing—original draft preparation: M.W., E.M., H.M., H.C.K., J.S. (Jacob Speybroeck), S.L., Q.K.T.; Writing—review and editing: M.W., E.M., H.M., S.T., H.C.K., J.S. (Jacob Speybroeck), M.M., C.M.B., J.S. (John Stillson), A.V.T., A.G., J.A., D.F., S.V.L., L.S., Q.K.T.; Supervision: M.W., S.L., Q.K.T., E.M., H.M.; All authors have read and agreed to the published version of the manuscript.

Funding

This research received no external funding.

Data Availability Statement

This study did not report any data.

Conflicts of Interest

Ernest Moore, Hunter Moore, Scott Thomas, and Hau Kwaan have received research grants from Haemonetics Corporation (Braintree, Massachusetts, USA).

Abbreviations

AABBAmerican Association of Blood Banks
BCTblood component therapy
CFCcoagulation factor concentrates
CSWBcold-stored whole blood
E-FIT1Early-Fibrinogen In Trauma 1
FEISTYFibrinogen Early In Severe Trauma study
FiiRSTFibrinogen in the initial Resuscitation of Severe Trauma
FinTICEuropean prehospital Fibrinogen in Trauma-Induced Coagulopathy
GD BCTgoal-directed blood component therapy
ISSinjury severity score
iTACTICTreatment Algorithms for the Correction of Trauma-Induced Coagulopathy
LTLRlow-titer, leukocyte-reduced
LTOWBlow-titer group O whole blood
MTmassive transfusion
MTPmassive transfusion protocol
PCCprothrombin complex concentrate
PLTplatelet
PPHpotentially preventable hemorrhage
PPOWERPragmatic, Prehospital, Type O, Whole Blood Early Resuscitation
PRBCpacked red blood cells
PROPPRPragmatic, Randomized Optimal Platelet and Plasma Ratios
RCTRandomized control trial
RETICReversal of Trauma-Induced Coagulopathy
ROTEMrotational thromboelastometry
STORHMSang Total pour la Reanimation des Hemorragies Massives
SWATShock, Whole Blood, and Assessment of TBI
TBItraumatic brain injury
TEGthromboelastography
THORTrauma Hemostasis and Oxygenation Research
TICtrauma-induced coagulopathy
VETviscoelastic test
WBwhole blood
WFWBwarm fresh whole blood

References

  1. Stubbs:, J.R.; Zielinski, M.D.; Jenkins, D. The state of the science of whole blood: Lessons learned at Mayo Clinic. Transfusion 2016, 56 (Suppl. 2), S173–S181. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  2. Zielinski, M.D.; Stubbs, J.R.; Berns, K.S.; Glassberg, E.; Murdock, A.D.; Shinar, E.; Sunde, G.A.; Williams, S.; Yazer, M.H.; Zietlow, S.; et al. Prehospital blood transfusion programs: Capabilities and lessons learned. J. Trauma Acute Care Surg. 2017, 82, S70–S78. [Google Scholar] [CrossRef] [PubMed]
  3. Cap, A.P.; Beckett, A.; Benov, A.; Borgman, M.; Chen, J.; Corley, J.B.; Doughty, H.; Fisher, A.; Glassberg, E.; Gonzales, R.; et al. Whole Blood Transfusion. Mil. Med. 2018, 183 (Suppl. 2), 44–51. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  4. Holcomb, J.B.; Jenkins, D.H. Get ready: Whole blood is back and it’s good for patients. Transfusion 2018, 58, 1821. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  5. Pivalizza, E.G.; Stephens, C.T.; Sridhar, S.; Gumbert, S.D.; Rossmann, S.; Bertholf, M.F.; Bai, Y.; Cotton, B.A. Whole Blood for Resuscitation in Adult Civilian Trauma in 2017: A Narrative Review. Anesth. Analg. 2018, 127, 157–162. [Google Scholar] [CrossRef] [PubMed]
  6. Yazer, M.H.; Cap, A.P.; Spinella, P.C.; Alarcon, L.; Triulzi, D.J. How do I implement a whole blood program for massively bleeding patients? Transfusion 2018, 58, 622–628. [Google Scholar] [CrossRef] [PubMed]
  7. Jenkins, D.; Stubbs, J.; Williams, S.; Berns, K.; Zielinski, M.; Strandenes, G.; Zietlow, S. Implementation and execution of civilian remote damage control resuscitation programs. Shock 2014, 41, 84–89. [Google Scholar] [CrossRef]
  8. Jenkins, D.H.; Rappold, J.F.; Badloe, J.F.; Berseus, O.; Blackbourne, L.; Brohi, K.H.; Butler, F.K.; Cap, A.P.; Cohen, M.J.; Davenport, R. Trauma hemostasis and oxygenation research position paper on remote damage control resuscitation: Definitions, current practice, and knowledge gaps. Shock 2014, 41, 3–12. [Google Scholar] [CrossRef] [Green Version]
  9. Sperry, J.L.; Early, B.; Buck, M.; Silfies, L. Shock, Whole blood and Assessment of TBI (SWAT); University of Pittsburgh: Pittsburgh, PA, USA, 2018. [Google Scholar]
  10. Yazer, M.H.; Seheult, J.; Kleinman, S.; Sloan, S.R.; Spinella, P.C. Who’s afraid of incompatible plasma? A balanced approach to the safe transfusion of blood products containing ABO-incompatible plasma. Transfusion 2018, 58, 532–538. [Google Scholar] [CrossRef]
  11. Holcomb, J.B.; Tilley, B.C.; Baraniuk, S.; Fox, E.E.; Wade, C.E.; Podbielski, J.M.; del Junco, D.J.; Brasel, K.J.; Bulger, E.M.; Callcut, R.A. Transfusion of plasma, platelets, and red blood cells in a 1:1:1 vs a 1:1:2 ratio and mortality in patients with severe trauma: The PROPPR randomized clinical trial. JAMA 2015, 313, 471–482. [Google Scholar] [CrossRef]
  12. Dzik, W. Misunderstanding the PROPPR trial. Transfusion 2017, 57, 2056. [Google Scholar] [CrossRef] [PubMed]
  13. Holcomb, J.B.; Donathan, D.P.; Cotton, B.A.; Del Junco, D.J.; Brown, G.; Wenckstern, T.V.; Podbielski, J.M.; Camp, E.A.; Hobbs, R.; Bai, Y. Prehospital Transfusion of Plasma and Red Blood Cells in Trauma Patients. Prehosp. Emerg. Care 2015, 19, 1–9. [Google Scholar] [CrossRef] [PubMed]
  14. Holcomb, J.B.; Hess, J.R.; Group, P.S. Response to: “Misunderstanding the PROPPR trial”. Transfusion 2017, 57, 2057–2058. [Google Scholar] [CrossRef] [PubMed]
  15. Rijnhout, T.W.H.; Wever, K.E.; Marinus, R.; Hoogerwerf, N.; Geeraedts, L.M.G., Jr.; Tan, E.C. Is prehospital blood transfusion effective and safe in haemorrhagic trauma patients? A systematic review and meta-analysis. Injury 2019, 50, 1017–1027. [Google Scholar] [CrossRef] [PubMed]
  16. Thies, K.-C.; Truhlář, A.; Keene, D.; Hinkelbein, J.; Rützler, K.; Brazzi, L.; Vivien, B. Pre-hospital blood transfusion–a survey on European practice. Scand. J. Trauma Resusc. Emerg. Med. 2020, 28, 1–8. [Google Scholar] [CrossRef] [PubMed]
  17. Vanderspurt, C.K.; Spinella, P.C.; Cap, A.P.; Hill, R.; Matthews, S.A.; Corley, J.B.; Gurney, J.M. The use of whole blood in US military operations in Iraq, Syria, and Afghanistan since the introduction of low-titer Type O whole blood: Feasibility, acceptability, challenges. Transfusion 2019, 59, 965–970. [Google Scholar] [CrossRef]
  18. Seheult, J.N.; Bahr, M.P.; Spinella, P.C.; Triulzi, D.J.; Yazer, M.H. The Dead Sea needs salt water… massively bleeding patients need whole blood: The evolution of blood product resuscitation. Transfus. Clin. Biol. 2019, 26, 174–179. [Google Scholar] [CrossRef]
  19. Zhu, C.S.; Pokorny, D.M.; Eastridge, B.J.; Nicholson, S.E.; Epley, E.; Forcum, J.; Long, T.; Miramontes, D.; Schaefer, R.; Shiels, M. Give the trauma patient what they bleed, when and where they need it: Establishing a comprehensive regional system of resuscitation based on patient need utilizing cold-stored, low-titer O+ whole blood. Transfusion 2019, 59, 1429–1438. [Google Scholar] [CrossRef] [Green Version]
  20. Leeper, C.M.; Yazer, M.H.; Cladis, F.P.; Saladino, R.; Triulzi, D.J.; Gaines, B.A. Use of Uncrossmatched Cold-Stored Whole Blood in Injured Children With Hemorrhagic Shock. JAMA Pediatrics 2018, 172, 491–492. [Google Scholar] [CrossRef] [Green Version]
  21. McGinity, A.C.; Zhu, C.S.; Greebon, L.; Xenakis, E.; Waltman, E.; Epley, E.; Cobb, D.; Jonas, R.; Nicholson, S.E.; Eastridge, B.J. Prehospital low-titer cold-stored whole blood: Philosophy for ubiquitous utilization of O-positive product for emergency use in hemorrhage due to injury. J. Trauma Acute Care Surg. 2018, 84, S115–S119. [Google Scholar] [CrossRef]
  22. Seheult, J.N.; Anto, V.; Alarcon, L.H.; Sperry, J.L.; Triulzi, D.J.; Yazer, M.H. Clinical outcomes among low-titer group O whole blood recipients compared to recipients of conventional components in civilian trauma resuscitation. Transfusion 2018, 58, 1838–1845. [Google Scholar] [CrossRef] [PubMed]
  23. Strandenes, G.; Berseus, O.; Cap, A.P.; Hervig, T.; Reade, M.; Prat, N.; Sailliol, A.; Gonzales, R.; Simon, C.D.; Ness, P.; et al. Low titer group O whole blood in emergency situations. Shock 2014, 41, 70–75. [Google Scholar] [CrossRef] [PubMed]
  24. Spinella, P.C. Warm fresh whole blood transfusion for severe hemorrhage: U.S. military and potential civilian applications. Crit. Care Med. 2008, 36, S340–345. [Google Scholar] [CrossRef] [PubMed]
  25. Seheult, J.N.; Triulzi, D.J.; Alarcon, L.H.; Sperry, J.L.; Murdock, A.; Yazer, M.H. Measurement of haemolysis markers following transfusion of uncrossmatched, low-titre, group O+ whole blood in civilian trauma patients: Initial experience at a level 1 trauma centre. Transfus. Med. 2017, 27, 30–35. [Google Scholar] [CrossRef]
  26. Spinella, P.C. Zero preventable deaths after traumatic injury: An achievable goal. J. Trauma Acute Care Surg. 2017, 82, S2–S8. [Google Scholar] [CrossRef]
  27. Condron, M.; Scanlan, M.; Schreiber, M. Massive transfusion of low-titer cold-stored O-positive whole blood in a civilian trauma setting. Transfusion 2019, 59, 927–930. [Google Scholar] [CrossRef]
  28. Cotton, B.A.; Podbielski, J.; Camp, E.; Welch, T.; del Junco, D.; Bai, Y.; Hobbs, R.; Scroggins, J.; Hartwell, B.; Kozar, R.A. A randomized controlled pilot trial of modified whole blood versus component therapy in severely injured patients requiring large volume transfusions. Ann. Surg. 2013, 258, 527–532; discussion 532–523. [Google Scholar] [CrossRef]
  29. Gallaher, J.R.; Dixon, A.; Cockcroft, A.; Grey, M.; Dewey, E.; Goodman, A.; Schreiber, M. Large volume transfusion with whole blood is safe compared with component therapy. J. Trauma Acute Care Surg. 2020, 89, 238–245. [Google Scholar] [CrossRef]
  30. Hazelton, J.P.; Cannon, J.W.; Zatorski, C.; Roman, J.S.; Moore, S.A.; Young, A.J.; Subramanian, M.; Guzman, J.F.; Fogt, F.; Moran, A.; et al. Cold-stored whole blood: A better method of trauma resuscitation? J. Trauma Acute Care Surg. 2019, 87, 1035–1041. [Google Scholar] [CrossRef]
  31. Ho, K.M.; Leonard, A.D. Lack of effect of unrefrigerated young whole blood transfusion on patient outcomes after massive transfusion in a civilian setting. Transfusion 2011, 51, 1669–1675. [Google Scholar] [CrossRef]
  32. Spinella, P.C.; Pidcoke, H.F.; Strandenes, G.; Hervig, T.; Fisher, A.; Jenkins, D.; Yazer, M.; Stubbs, J.; Murdock, A.; Sailliol, A. Whole blood for hemostatic resuscitation of major bleeding. Transfusion 2016, 56, S190–202. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  33. Williams, J.; Merutka, N.; Meyer, D.; Bai, Y.; Prater, S.; Cabrera, R.; Holcomb, J.B.; Wade, C.E.; Love, J.D.; Cotton, B.A. Safety profile and impact of low-titer group O whole blood for emergency use in trauma. J. Trauma Acute Care Surg. 2020, 88, 87–93. [Google Scholar] [CrossRef] [PubMed]
  34. Yazer, M.H.; Spinella, P.C. Review of low titre group O whole blood use for massively bleeding patients around the world in 2019. ISBT Sci. Ser. 2019, 14, 276–281. [Google Scholar] [CrossRef]
  35. Fadeyi, E.A.; Saha, A.K.; Naal, T.; Martin, H.; Fenu, E.; Simmons, J.H.; Jones, M.R.; Pomper, G.J. A comparison between leukocyte reduced low titer whole blood vs non-leukocyte reduced low titer whole blood for massive transfusion activation. Transfusion 2020. [Google Scholar] [CrossRef] [PubMed]
  36. Hanna, K.; Bible, L.; Chehab, M.; Asmar, S.; Douglas, M.; Ditillo, M.; Castanon, L.; Tang, A.; Joseph, B. Nationwide analysis of whole blood hemostatic resuscitation in civilian trauma. J. Trauma Acute Care Surg. 2020, 89, 329–335. [Google Scholar] [CrossRef]
  37. Shea, S.M.; Staudt, A.M.; Thomas, K.A.; Schuerer, D.; Mielke, J.E.; Folkerts, D.; Lowder, E.; Martin, C.; Bochicchio, G.V.; Spinella, P.C. The use of low-titer group O whole blood is independently associated with improved survival compared to component therapy in adults with severe traumatic hemorrhage. Transfusion 2020, 60, S2–S9. [Google Scholar] [CrossRef]
  38. Leeper, C.M.; Yazer, M.H.; Triulzi, D.J.; Neal, M.D.; Gaines, B.A. Whole Blood is Superior to Component Transfusion for Injured Children: A Propensity Matched Analysis. Ann. Surg. 2020, 272, 590–594. [Google Scholar] [CrossRef]
  39. Armand, R.; Hess, J.R. Treating coagulopathy in trauma patients. Transfus. Med. Rev. 2003, 17, 223–231. [Google Scholar] [CrossRef]
  40. Moore, E.E.; Moore, H.B.; Chapman, M.P.; Gonzalez, E.; Sauaia, A. Goal-directed hemostatic resuscitation for trauma induced coagulopathy: Maintaining homeostasis. J. Trauma Acute Care Surg. 2018, 84 (Suppl. 1), S35–S40. [Google Scholar] [CrossRef]
  41. Chang, R.; Eastridge, B.J.; Holcomb, J.B. Remote Damage Control Resuscitation in Austere Environments. Wilderness Environ. Med. 2017, 28, S124–S134. [Google Scholar] [CrossRef] [Green Version]
  42. Gonzalez, E.; Moore, E.E.; Moore, H.B.; Chapman, M.P.; Chin, T.L.; Ghasabyan, A.; Wohlauer, M.V.; Barnett, C.C.; Bensard, D.D.; Biffl, W.L.; et al. Goal-directed Hemostatic Resuscitation of Trauma-induced Coagulopathy: A Pragmatic Randomized Clinical Trial Comparing a Viscoelastic Assay to Conventional Coagulation Assays. Ann. Surg. 2016, 263, 1051–1059. [Google Scholar] [CrossRef] [PubMed]
  43. Tapia, N.M.; Chang, A.; Norman, M.; Welsh, F.; Scott, B.; Wall, M.J., Jr.; Mattox, K.L.; Suliburk, J. TEG-guided resuscitation is superior to standardized MTP resuscitation in massively transfused penetrating trauma patients. J. Trauma Acute Care Surg. 2013, 74, 378–385. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  44. Howley, I.W.; Haut, E.R.; Jacobs, L.; Morrison, J.J.; Scalea, T.M. Is thromboelastography (TEG)-based resuscitation better than empirical 1:1 transfusion? Trauma Surg. Acute Care Open 2018, 3, e000140. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  45. Hoffman, M.; Monroe III, D.M. A cell-based model of hemostasis. Thrombosis and Haemostasis 2001, 85, 958–965. [Google Scholar] [PubMed]
  46. Walsh, M.; Thomas, S.; Kwaan, H.; Aversa, J.; Anderson, S.; Sundararajan, R.; Zimmer, D.; Bunch, C.; Stillson, J.; Draxler, D.; et al. Modern methods for monitoring hemorrhagic resuscitation in the United States: Why the delay? J. Trauma Acute Care Surg. 2020, 89, 1018–1022. [Google Scholar] [CrossRef] [PubMed]
  47. Schochl, H.; Maegele, M.; Voelckel, W. Fixed ratio versus goal-directed therapy in trauma. Curr. Opin. Anaesthesiol. 2016, 29, 234–244. [Google Scholar] [CrossRef] [PubMed]
  48. Kornblith, L.Z.; Moore, H.B.; Cohen, M.J. Trauma-induced coagulopathy: The past, present, and future. J. Thromb. Haemost. 2019, 17, 852–862. [Google Scholar] [CrossRef]
  49. Maegele, M.; Lefering, R.; Yucel, N.; Tjardes, T.; Rixen, D.; Paffrath, T.; Simanski, C.; Neugebauer, E.; Bouillon, B.; AG Polytrauma of the German Trauma Society (DGU). Early coagulopathy in multiple injury: An analysis from the German Trauma Registry on 8724 patients. Injury 2007, 38, 298–304. [Google Scholar] [CrossRef]
  50. Brohi, K.; Singh, J.; Heron, M.; Coats, T. Acute traumatic coagulopathy. J. Trauma 2003, 54, 1127–1130. [Google Scholar] [CrossRef] [Green Version]
  51. Chang, R.; Cardenas, J.C.; Wade, C.E.; Holcomb, J.B. Advances in the understanding of trauma-induced coagulopathy. Blood 2016, 128, 1043–1049. [Google Scholar] [CrossRef] [Green Version]
  52. Cochrane, C.; Chinna, S.; Um, J.Y.; Dias, J.D.; Hartmann, J.; Bradley, J.; Brooks, A. Site-Of-Care Viscoelastic Assay in Major Trauma Improves Outcomes and Is Cost Neutral Compared with Standard Coagulation Tests. Diagnostics 2020, 10, 248652. [Google Scholar] [CrossRef] [PubMed]
  53. Dobson, G.P.; Letson, H.L.; Sharma, R.; Sheppard, F.R.; Cap, A.P. Mechanisms of early trauma-induced coagulopathy: The clot thickens or not? J. Trauma Acute Care Surg. 2015, 79, 301–309. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  54. Johansson, P.I.; Stensballe, J.; Oliveri, R.; Wade, C.E.; Ostrowski, S.R.; Holcomb, J.B. How I treat patients with massive hemorrhage. Blood 2014, 124, 3052–3058. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  55. Johansson, P.I.; Stissing, T.; Bochsen, L.; Ostrowski, S.R. Thrombelastography and tromboelastometry in assessing coagulopathy in trauma. Scand. J. Trauma Resusc. Emerg. Med. 2009, 17, 45. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  56. MacLeod, J.B.; Lynn, M.; McKenney, M.G.; Cohn, S.M.; Murtha, M. Early coagulopathy predicts mortality in trauma. J. Trauma Acute Care Surg. 2003, 55, 39–44. [Google Scholar] [CrossRef] [PubMed]
  57. Kaufmann, C.R.; Dwyer, K.M.; Crews, J.D.; Dols, S.J.; Trask, A.L. Usefulness of thrombelastography in assessment of trauma patient coagulation. J. Trauma 1997, 42, 716–720; discussion 720–722. [Google Scholar] [CrossRef] [PubMed]
  58. Collins, P.W.; Cannings-John, R.; Bruynseels, D.; Mallaiah, S.; Dick, J.; Elton, C.; Weeks, A.D.; Sanders, J.; Aawar, N.; Townson, J. Viscoelastometric-guided early fibrinogen concentrate replacement during postpartum haemorrhage: OBS2, a double-blind randomized controlled trial. BJA Br. J. Anaesth. 2017, 119, 411–421. [Google Scholar] [CrossRef] [Green Version]
  59. Holcomb, J.B.; Minei, K.M.; Scerbo, M.L.; Radwan, Z.A.; Wade, C.E.; Kozar, R.A.; Gill, B.S.; Albarado, R.; McNutt, M.K.; Khan, S. Admission rapid thrombelastography can replace conventional coagulation tests in the emergency department: Experience with 1974 consecutive trauma patients. Ann. Surg. 2012, 256, 476–486. [Google Scholar] [CrossRef]
  60. Hunt, B.J.; Lyons, G. Thromboelastography should be available in every labour ward. Int. J. Obstet. Anesth. 2005, 14, 324–325. [Google Scholar] [CrossRef]
  61. Subramanian, M.; Kaplan, L.J.; Cannon, J.W. Thromboelastography-Guided Resuscitation of the Trauma Patient. JAMA Surg. 2019, 154, 1152–1153. [Google Scholar] [CrossRef]
  62. Etchill, E.; Sperry, J.; Zuckerbraun, B.; Alarcon, L.; Brown, J.; Schuster, K.; Kaplan, L.; Piper, G.; Peitzman, A.; Neal, M.D. The confusion continues: Results from an American Association for the Surgery of Trauma survey on massive transfusion practices among United States trauma centers. Transfusion 2016, 56, 2478–2486. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  63. Gorlinger, K.; Fries, D.; Dirkmann, D.; Weber, C.F.; Hanke, A.A.; Schochl, H. Reduction of Fresh Frozen Plasma Requirements by Perioperative Point-of-Care Coagulation Management with Early Calculated Goal-Directed Therapy. Transfus. Med. Hemother. 2012, 39, 104–113. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  64. Walsh, M.; Thomas, S.; Moore, E.; Moore, H.; Piscoya, A.; Hake, D.; Son, M.; Pohlman, T.; Wegner, J.; Bryant, J.; et al. Tranexamic Acid for Trauma Resuscitation in the United States of America. Semin. Thromb. Hemost. 2017, 43, 213–223. [Google Scholar] [PubMed]
  65. Spahn, D.R.; Bouillon, B.; Cerny, V.; Coats, T.J.; Duranteau, J.; Fernandez-Mondejar, E.; Filipescu, D.; Hunt, B.J.; Komadina, R.; Nardi, G. Management of bleeding and coagulopathy following major trauma: An updated European guideline. Crit. Care 2013, 17, R76. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  66. Hess, J.R.; Lindell, A.L.; Stansbury, L.G.; Dutton, R.P.; Scalea, T.M. The prevalence of abnormal results of conventional coagulation tests on admission to a trauma center. Transfusion 2009, 49, 34–39. [Google Scholar] [CrossRef]
  67. Wells, D.; Hess, J.R.; Sabath, D.E. Thromboelastography in Trauma: A 1-Year Institutional Experience. Am. J. Clin. Pathol. 2019, 152, S1–S2. [Google Scholar] [CrossRef]
  68. Hartmann, J.; Walsh, M.; Grisoli, A.; Thomas, A.V.; Shariff, F.; McCauley, R.; Lune, S.V.; Zackariya, N.; Patel, S.; Farrell, M.S. Diagnosis and Treatment of Trauma-Induced Coagulopathy by Viscoelastography. Semin. Thromb. Hemost. 2020, 46, 134–146. [Google Scholar] [CrossRef]
  69. Curry, N.S.; Davenport, R.; Pavord, S.; Mallett, S.V.; Kitchen, D.; Klein, A.A.; Maybury, H.; Collins, P.W.; Laffan, M. The use of viscoelastic haemostatic assays in the management of major bleeding: A British Society for Haematology Guideline. Br. J. Haematol. 2018, 182, 789–806. [Google Scholar] [CrossRef] [Green Version]
  70. Schenk, B.; Gorlinger, K.; Treml, B.; Tauber, H.; Fries, D.; Niederwanger, C.; Oswald, E.; Bachler, M. A comparison of the new ROTEM((R)) sigma with its predecessor, the ROTEMdelta. Anaesthesia 2019, 74, 348–356. [Google Scholar] [CrossRef]
  71. Lloyd-Donald, P.; Churilov, L.; Zia, F.; Bellomo, R.; Hart, G.; McCall, P.; Mårtensson, J.; Glassford, N.; Weinberg, L. Assessment of agreement and interchangeability between the TEG5000 and TEG6S thromboelastography haemostasis analysers: A prospective validation study. BMC Anesthesiol. 2019, 19, 45. [Google Scholar] [CrossRef]
  72. Gorlinger, K.; Perez-Ferrer, A.; Dirkmann, D.; Saner, F.; Maegele, M.; Calatayud, A.A.P.; Kim, T.Y. The role of evidence-based algorithms for rotational thromboelastometry-guided bleeding management. Korean J. Anesthesiol. 2019, 72, 297–322. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  73. Veigas, P.V.; Callum, J.; Rizoli, S.; Nascimento, B.; da Luz, L.T. A systematic review on the rotational thrombelastometry (ROTEM(R)) values for the diagnosis of coagulopathy, prediction and guidance of blood transfusion and prediction of mortality in trauma patients. Scand. J. Trauma Resusc. Emerg. Med. 2016, 24, 114. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  74. Wafaisade, A.; Lefering, R.; Maegele, M.; Lendemans, S.; Flohe, S.; Hussmann, B.; Defosse, J.M.; Probst, C.; Paffrath, T.; Bouillon, B.; et al. Coagulation management of bleeding trauma patients is changing in German trauma centers: An analysis from the trauma registry of the German Society for Trauma Surgery. J. Trauma Acute Care Surg. 2012, 72, 936–942. [Google Scholar] [CrossRef] [PubMed]
  75. Johansson, P.I. Goal-directed hemostatic resuscitation for massively bleeding patients: The Copenhagen concept. Transfus. Apher. Sci. 2010, 43, 401–405. [Google Scholar] [CrossRef] [PubMed]
  76. Nardi, G.; Agostini, V.; Rondinelli, B.; Russo, E.; Bastianini, B.; Bini, G.; Bulgarelli, S.; Cingolani, E.; Donato, A.; Gambale, G.; et al. Trauma-induced coagulopathy: Impact of the early coagulation support protocol on blood product consumption, mortality and costs. Crit. Care 2015, 19, 83. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  77. Fenger-Eriksen, C.; Lindberg-Larsen, M.; Christensen, A.Q.; Ingerslev, J.; Sorensen, B. Fibrinogen concentrate substitution therapy in patients with massive haemorrhage and low plasma fibrinogen concentrations. Br. J. Anaesth. 2008, 101, 769–773. [Google Scholar] [CrossRef] [Green Version]
  78. Innerhofer, P.; Westermann, I.; Tauber, H.; Breitkopf, R.; Fries, D.; Kastenberger, T.; El Attal, R.; Strasak, A.; Mittermayr, M. The exclusive use of coagulation factor concentrates enables reversal of coagulopathy and decreases transfusion rates in patients with major blunt trauma. Injury 2013, 44, 209–216. [Google Scholar] [CrossRef]
  79. Lim, R., Jr.; Olcott IV, C.; Robinsion, A.; Blaisedale, F. Platelet response and coagulation changes following massive blood replacement. J. Trauma Acute Care Surg. 1973, 13, 577–582. [Google Scholar] [CrossRef]
  80. Mann, K.G.; Brummel, K.; Butenas, S. What is all that thrombin for? J. Thromb. Haemost. 2003, 1, 1504–1514. [Google Scholar] [CrossRef]
  81. Martini, W.Z.; Rodriguez, C.M.; Cap, A.P.; Dubick, M.A. Efficacy of resuscitation with fibrinogen concentrate and platelets in traumatic hemorrhage swine model. J. Trauma Acute Care Surg. 2020, 89, S137–S145. [Google Scholar]
  82. Rahe-Meyer, N.; Solomon, C.; Hanke, A.; Schmidt, D.S.; Knoerzer, D.; Hochleitner, G.; Sorensen, B.; Hagl, C.; Pichlmaier, M. Effects of fibrinogen concentrate as first-line therapy during major aortic replacement surgery: A randomized, placebo-controlled trial. Anesthesiology 2013, 118, 40–50. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  83. Sadeghi, M.; Atefyekta, R.; Azimaraghi, O.; Marashi, S.M.; Aghajani, Y.; Ghadimi, F.; Spahn, D.R.; Movafegh, A. A randomized, double blind trial of prophylactic fibrinogen to reduce bleeding in cardiac surgery. Braz. J. Anesthesiol. 2014, 64, 253–257. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  84. Yamamoto, K.; Usui, A.; Takamatsu, J. Fibrinogen concentrate administration attributes to significant reductions of blood loss and transfusion requirements in thoracic aneurysm repair. J. Cardiothorac. Surg. 2014, 9, 90. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  85. Marsden, M.; Benger, J.; Brohi, K.; Curry, N.; Foley, C.; Green, L.; Lucas, J.; Rossetto, A.; Stanworth, S.; Thomas, H.; et al. Coagulopathy, cryoprecipitate and CRYOSTAT-2: Realising the potential of a nationwide trauma system for a national clinical trial. Br. J. Anaesth. 2019, 122, 164–169. [Google Scholar] [CrossRef] [Green Version]
  86. Fries, D. The early use of fibrinogen, prothrombin complex concentrate, and recombinant-activated factor VIIa in massive bleeding. Transfusion 2013, 53, 91S–95S. [Google Scholar] [CrossRef]
  87. Innerhofer, P.; Fries, D.; Mittermayr, M.; Innerhofer, N.; von Langen, D.; Hell, T.; Gruber, G.; Schmid, S.; Friesenecker, B.; Lorenz, I.H. Reversal of trauma-induced coagulopathy using first-line coagulation factor concentrates or fresh frozen plasma (RETIC): A single-centre, parallel-group, open-label, randomised trial. Lancet Haematol. 2017, 4, e258–e271. [Google Scholar] [CrossRef]
  88. Mengoli, C.; Franchini, M.; Marano, G.; Pupella, S.; Vaglio, S.; Marietta, M.; Liumbruno, G.M. The use of fibrinogen concentrate for the management of trauma-related bleeding: A systematic review and meta-analysis. Blood Transfus. 2017, 15, 318–324. [Google Scholar]
  89. Nascimento, B.; Callum, J.; Tien, H.; Peng, H.; Rizoli, S.; Karanicolas, P.; Alam, A.; Xiong, W.; Selby, R.; Garzon, A.M. Fibrinogen in the initial resuscitation of severe trauma (FiiRST): A randomized feasibility trial. Br. J. Anaesth. 2016, 117, 775–782. [Google Scholar] [CrossRef] [Green Version]
  90. Schochl, H.; Nienaber, U.; Maegele, M.; Hochleitner, G.; Primavesi, F.; Steitz, B.; Arndt, C.; Hanke, A.; Voelckel, W.; Solomon, C. Transfusion in trauma: Thromboelastometry-guided coagulation factor concentrate-based therapy versus standard fresh frozen plasma-based therapy. Crit. Care 2011, 15, R83. [Google Scholar] [CrossRef] [Green Version]
  91. Yamamoto, K.; Yamaguchi, A.; Sawano, M.; Matsuda, M.; Anan, M.; Inokuchi, K.; Sugiyama, S. Pre-emptive administration of fibrinogen concentrate contributes to improved prognosis in patients with severe trauma. Trauma Surg. Acute Care Open 2016, 1, e000037. [Google Scholar] [CrossRef] [Green Version]
  92. Curry, N.; Foley, C.; Wong, H.; Mora, A.; Curnow, E.; Zarankaite, A.; Hodge, R.; Hopkins, V.; Deary, A.; Ray, J. Early fibrinogen concentrate therapy for major haemorrhage in trauma (E-FIT 1): Results from a UK multi-centre, randomised, double blind, placebo-controlled pilot trial. Crit. Care 2018, 22, 1–9. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  93. Maegele, M.; Zinser, M.; Schlimp, C.; Schochl, H.; Fries, D. Injectable hemostatic adjuncts in trauma: Fibrinogen and the FIinTIC study. J. Trauma Acute Care Surg. 2015, 78, S76–82. [Google Scholar] [CrossRef] [PubMed]
  94. Spahn, D.R.; Bouillon, B.; Cerny, V.; Duranteau, J.; Filipescu, D.; Hunt, B.J.; Komadina, R.; Maegele, M.; Nardi, G.; Riddez, L. The European guideline on management of major bleeding and coagulopathy following trauma: Fifth edition. Crit. Care 2019, 23, 98. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  95. Ziegler, B.; Bachler, M.; Haberfellner, H.; Niederwanger, C.; Innerhofer, P.; Hell, T.; Kaufmann, M.; Maegele, M.; Martinowitz, U.; Nebl, C.; et al. Efficacy of prehospital administration of fibrinogen concentrate in trauma patients bleeding or presumed to bleed (FIinTIC): A multicentre, double-blind, placebo-controlled, randomised pilot study. Eur. J. Anaesthesiol. EJA 2019, 37, 1–10. [Google Scholar] [CrossRef] [PubMed]
  96. Kaserer, A.; Casutt, M.; Sprengel, K.; Seifert, B.; Spahn, D.R.; Stein, P. Comparison of two different coagulation algorithms on the use of allogenic blood products and coagulation factors in severely injured trauma patients: A retrospective, multicentre, observational study. Scand. J. Trauma Resusc. Emerg. Med. 2018, 26, 4. [Google Scholar] [CrossRef] [Green Version]
  97. Winearls, J.; Wullschleger, M.; Wake, E.; Hurn, C.; Furyk, J.; Ryan, G.; Trout, M.; Walsham, J.; Holley, A.; Cohen, J. Fibrinogen Early In Severe Trauma studY (FEISTY): Study protocol for a randomised controlled trial. Trials 2017, 18, 1–11. [Google Scholar] [CrossRef] [Green Version]
  98. Chipman, A.M.; Jenne, C.; Wu, F.; Kozar, R.A. Contemporary resuscitation of hemorrhagic shock: What will the future hold? Am. J. Surg. 2020, 220, 580–588. [Google Scholar] [CrossRef]
  99. Baksaas-Aasen, K.; Gall, L.S.; Stensballe, J.; Juffermans, N.P.; Curry, N.; Maegele, M.; Brooks, A.; Rourke, C.; Gillespie, S.; Murphy, J. Viscoelastic haemostatic assay augmented protocols for major trauma haemorrhage (ITACTIC): A randomized, controlled trial. SSRN Electron. J. 2020, 47. [Google Scholar] [CrossRef]
  100. Stettler, G.R.; Moore, E.E.; Moore, H.B.; Nunns, G.R.; Silliman, C.C.; Banerjee, A.; Sauaia, A. Redefining postinjury fibrinolysis phenotypes using two viscoelastic assays. J. Trauma Acute Care Surg. 2019, 86, 679–685. [Google Scholar] [CrossRef]
  101. Stettler, G.R.; Moore, E.E.; Nunns, G.R.; Chandler, J.; Peltz, E.; Silliman, C.C.; Banerjee, A.; Sauaia, A. Rotational thromboelastometry thresholds for patients at risk for massive transfusion. J. Surg. Res. 2018, 228, 154–159. [Google Scholar] [CrossRef]
  102. Mitra, B.; Cameron, P.A.; Gruen, R.L.; Mori, A.; Fitzgerald, M.; Street, A. The definition of massive transfusion in trauma: A critical variable in examining evidence for resuscitation. Eur. J. Emerg. Med. 2011, 18, 137–142. [Google Scholar] [CrossRef] [PubMed]
  103. Nunns, G.R.; Moore, E.E.; Chapman, M.P.; Moore, H.B.; Stettler, G.R.; Peltz, E.; Burlew, C.C.; Silliman, C.C.; Banerjee, A.; Sauaia, A. The hypercoagulability paradox of chronic kidney disease: The role of fibrinogen. Am. J. Surg. 2017, 214, 1215–1218. [Google Scholar] [CrossRef] [PubMed]
  104. Kalkwarf, K.J.; Drake, S.A.; Yang, Y.; Thetford, C.; Myers, L.; Brock, M.; Wolf, D.A.; Persse, D.; Wade, C.E.; Holcomb, J.B. Bleeding to death in a big city: An analysis of all trauma deaths from hemorrhage in a metropolitan area during 1 year. J. Trauma Acute Care Surg. 2020, 89, 716–722. [Google Scholar] [PubMed]
  105. Bieler, D.; Franke, A.F.; Hentsch, S.; Paffrath, T.; Willms, A.; Lefering, R.; Kollig, E.W.; TraumaRegister, D.G.U. Gunshot and stab wounds in Germany—Epidemiology and outcome: Analysis from the TraumaRegister DGU(R). Unfallchirurg 2014, 117, 995–1004. [Google Scholar] [CrossRef] [PubMed]
  106. Dijkink, S.; Krijnen, P.; Hage, A.; Van der Wilden, G.M.; Kasotakis, G.; Hartog, D.D.; Salim, A.; Goslings, J.C.; Bloemers, F.W.; Rhemrev, S.J.; et al. Differences in Characteristics and Outcome of Patients with Penetrating Injuries in the USA and the Netherlands: A Multi-institutional Comparison. World J. Surg. 2018, 42, 3608–3615. [Google Scholar] [CrossRef] [Green Version]
  107. Al-Shaqsi, S. Models of International Emergency Medical Service (EMS) Systems. Oman Med. J. 2010, 25, 320. [Google Scholar] [CrossRef]
  108. Oakeshott, J.E.; Griggs, J.E.; Wareham, G.M.; Lyon, R.M. Feasibility of prehospital freeze-dried plasma administration in a UK Helicopter Emergency Medical Service. Eur J. Emerg. Med. 2019, 26, 373–378. [Google Scholar] [CrossRef]
  109. Curry, N.S.; Davenport, R. Transfusion strategies for major haemorrhage in trauma. Br. J. Haematol. 2019, 184, 508–523. [Google Scholar] [CrossRef] [Green Version]
  110. Rourke, C.; Curry, N.; Khan, S.; Taylor, R.; Raza, I.; Davenport, R.; Stanworth, S.; Brohi, K. Fibrinogen levels during trauma hemorrhage, response to replacement therapy, and association with patient outcomes. J. Thromb. Haemost. 2012, 10, 1342–1351. [Google Scholar] [CrossRef]
  111. Fries, D.; Krismer, A.; Klingler, A.; Streif, W.; Klima, G.; Wenzel, V.; Haas, T.; Innerhofer, P. Effect of fibrinogen on reversal of dilutional coagulopathy: A porcine model. Br. J. Anaesth. 2005, 95, 172–177. [Google Scholar] [CrossRef] [Green Version]
  112. Gorlinger, K.; Dirkmann, D.; Hanke, A.A. Potential value of transfusion protocols in cardiac surgery. Curr. Opin. Anaesthesiol. 2013, 26, 230–243. [Google Scholar] [CrossRef] [PubMed]
  113. Görlinger, K.; Dirkmann, D.; Hanke, A.A.; Kamler, M.; Kottenberg, E.; Thielmann, M.; Jakob, H.; Peters, J. First-Line Therapy With Coagulation Factor Concentrates Combined With Point-of-Care Coagulation Testing is Associated With Decreased Allogeneic Blood Transfusion in Cardiovascular Surgery. Surv. Anesthesiol. 2012, 56, 163–164. [Google Scholar] [CrossRef]
  114. Lier, H.; Vorweg, M.; Hanke, A.; Gorlinger, K. Thromboelastometry guided therapy of severe bleeding. Essener Runde algorithm. Hamostaseologie 2013, 33, 51–61. [Google Scholar] [PubMed]
  115. Schöchl, H.; Voelckel, W.; Schlimp, C. Management of traumatic haemorrhage—The European perspective. Anaesthesia 2015, 70, 102–107, e135–e137. [Google Scholar] [CrossRef] [PubMed]
  116. Trzebicki, J.; Flakiewicz, E.; Kosieradzki, M.; Blaszczyk, B.; Kołacz, M.; Jureczko, L.; Pacholczyk, M.; Chmura, A.; Lagiewska, B.; Lisik, W. The use of thromboelastometry in the assessment of hemostasis during orthotopic liver transplantation reduces the demand for blood products. Ann. Transplant. 2010, 15, 19–24. [Google Scholar] [PubMed]
  117. Wang, S.-C.; Shieh, J.-F.; Chang, K.-Y.; Chu, Y.-C.; Liu, C.-S.; Loong, C.-C.; Chan, K.-H.; Mandell, S.; Tsou, M.-Y. Thromboelastography-Guided Transfusion Decreases Intraoperative Blood Transfusion during Orthotopic Liver Transplantation: Randomized Clinical Trial. Transplant. Proc. 2010, 42, 2590–2593. [Google Scholar] [CrossRef] [PubMed]
  118. Fenger-Eriksen, C.; Fries, D.; David, J.-S.; Bouzat, P.; Lance, M.D.; Grottke, O.; Spahn, D.R.; Schoechl, H.; Maegele, M. Pre-hospital plasma transfusion: A valuable coagulation support or an expensive fluid therapy? BioMed Central 2019, 23, 238. [Google Scholar] [CrossRef] [Green Version]
  119. Gauss, T.; Lamblin, A.; Bouzat, P. The Twilight Zone: Ten beliefs about viscoelastic tests. Anaesth. Crit. Care Pain Med. 2019, 38, 449–450. [Google Scholar] [CrossRef]
  120. Schochl, H.; Nienaber, U.; Hofer, G.; Voelckel, W.; Jambor, C.; Scharbert, G.; Kozek-Langenecker, S.; Solomon, C. Goal-directed coagulation management of major trauma patients using thromboelastometry (ROTEM)-guided administration of fibrinogen concentrate and prothrombin complex concentrate. Crit. Care 2010, 14, R55. [Google Scholar] [CrossRef] [Green Version]
  121. Bugaev, N.; Como, J.J.; Golani, G.; Freeman, J.J.; Sawhney, J.S.; Vatsaas, C.J.; Yorkgitis, B.K.; Kreiner, L.A.; Garcia, N.M.; Aziz, H.A.; et al. Thromboelastography and rotational thromboelastometry in bleeding patients with coagulopathy: Practice management guideline from the Eastern Association for the Surgery of Trauma. J. Trauma Acute Care Surg. 2020, 89, 999–1017. [Google Scholar] [CrossRef]
  122. Espinosa, A.; Seghatchian, J. What is happening? The evolving role of the blood bank in the management of the bleeding patient: The impact of TEG as an early diagnostic predictor for bleeding. Transfus. Apher. Sci. 2014, 51, 105–110. [Google Scholar] [CrossRef] [PubMed]
  123. Grottke, O.; Levy, J.H. Prothrombin complex concentrates in trauma and perioperative bleeding. J. Am. Soc. Anthesiol. 2015, 122, 923–931. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  124. Sperry, J. Pragmatic Prehospital Group O Whole Blood Early Resuscitation (PPOWER) Trial: A Prospective, Interventional, Randomized, 3 Year, Pilot Clinical Trial; National Heart, Lung, and Blood Institute (NHLBI): Bethesda, MD, USA, 2018.
  125. Ausset, S.; Pouget, T.; Begué, S.; Gross, S.; Martinaud, C.; Tiberghien, P. La prise en charge transfusionnelle de l’hémorragie massive: étude STORHM. Trans. Clin. Biol. 2019, 26, S24. [Google Scholar] [CrossRef]
  126. Walsh, M.; Fries, D.; Moore, E.; Moore, H.; Thomas, S.; Kwaan, H.C.; Marsee, M.K.; Grisoli, A.; McCauley, R.; Lune, S.V. Whole blood for civilian urban trauma resuscitation: Historical, present, and future considerations. Semin. Thromb. Hemost. 2020, 46, 221–234. [Google Scholar] [CrossRef] [PubMed]
Table
Table 1. Studies of WB in the Civilian Population.
Table 1. Studies of WB in the Civilian Population.
StudyNumber of Patients Receiving WBStudy DesignDescriptionResults
Cotton et al. [28]55RCTSingle-center, RCT comparing modified WB and component therapyNo difference in 30 day mortality. Possible transfusion benefit in TBI.
Williams et al. [33]198Comparative clinical prospective therapeutic studyComparison of LTOWB versus BCT in prehospital and ED setting for trauma patientsLTOWB received less post-ED blood products with equivocally mortality benefit.
Hanna et al. [36]280Retrospective cohort analysisAnalysis of 2015–2016 ACS TQIP database comparing patients in hemorrhagic shock and given at least one unit of PRBCs or WB (note this likely includes patients from other studies)WB associated with improved 24 h mortality overall and improved in-hospital mortality in subgroups with penetrating mechanism and those without severe head injury.
Ho and Leonard [31]77Retrospective cohort studyUnrefrigerated young WB transfusion for patients requiring massive transfusion in a civilian settingNo benefit (overall survival and transfusion were equivalent)
Leeper et al. [38]28Propensity matched cohortPropensity matched cohort of children over 1 yearNo difference in mortality. Improved indices of shock and coagulopathy.
Seheult et al. [22]172Retrospective case–control analysisSafety analysis of LTOWB patients by blood groupNo mortality difference, similar clinical outcomes across groups, no increased hemolysis noted at 24 h in nongroup O patients.
Fadeyi et al. [35]167Retrospective cohortComparison trauma patient receiving LTOWB with leuko-reduced LTOWBNonstatistically significant 6% increased mortality in leuko-reduced LTOWB (p = 0.185).
Hazelton et al. [30]107Dual-center case-match studyMatching analysis for patients who received CSWB vs. BCT for hemodynamic parameters, hemoglobin and hematocrit at 24 h, trauma bay mortality, and 30 day mortalityCSWB associated with improved trauma bay survival and higher mean hemoglobin value at 24 h.
No difference in the amount of blood products transfused at 4 and 24 h periods.No difference in 30 day mortality between the two groups.
Shea et al. [37]44Prospective observationalBefore-and-after comparison of trauma patient requiring activation of massive transfusion before and after implementation of LTOWB MTP (up to 8 LTOWB unit)No difference of absolute mortality between groups. Post-hoc multivariate regression showed improved adjusted mortality in LTOWB group. Authors argue for effect mediation based on ROTEM parameters.
Gallaher et al. [29]42Retrospective observationalBefore-and-after comparison of mortality in trauma patients receiving blood products during implementation of LTOWB programLTOWB did not alter 30 day mortality, nonstatistically significant increase in total blood products, and no difference in lab values at 48 h.
Zielinski et al. [2]24 Mayo
22 Pittsburgh 73 Royal Caribbean		Retrospective observational Describes the THOR network prehospital WB programs including Mayo Clinic and Allegheny General Hospital and WFWB transfusion on Royal Caribbean cruiseObservation only.
Overall mortality in patients who received WB 31%.
Seheult et al. [25]44Observational studyHemolysis markers in group O and nongroup O recipients of platelet replete, uncrossmatched CSWBNo difference in hemolysis markers across groups.
Zhu et al. [19]30Retrospective observationalDescriptive study of prehospital WB transfusion implementation which included transfusion of 25 adults and 5 pediatric patientsObservational.
Mortality in adult: 36%; mean ISS: 29. Mortality in pediatric: 20%; mean ISS: 29.
Mean transport time, 37 min.
Leeper et al. [20]18Retrospective observationalPediatric uncrossmatched LTOWB transfusion for hemorrhagic shockISS: 34. Mortality 44%.
Condron et al. [27]1Case reportCase report of massive transfusion using 38 units of LTOWB in addition to MTP with blood componentsN/A
Abbreviations: ACS, American College of Surgeons; BCT, blood component therapy; CSWB, cold-stored whole blood; ED, emergency department; ISS, injury severity score; LTOWB, low-titer group O whole blood; MTP, massive transfusion protocol; PRBCs, packed red blood cells; RCT, randomized controlled trial; ROTEM, rotational thromboelastometry; TBI, traumatic brain injury; THOR, Trauma Hemostasis and Oxygenation Research; TQIP, Trauma Quality Improvement Program; WB, whole blood; WFWB, warm fresh whole blood.
Table
Table 2. Advantages and disadvantages of whole blood vs. fixed ratio vs. VET-guided BCT.
Table 2. Advantages and disadvantages of whole blood vs. fixed ratio vs. VET-guided BCT.
AdvantagesDisadvantages
Whole blood
-
Simple protocols and uniform dosing
-
Easy to administer in prehospital and hospital setting
-
Provides all blood components; avoids hemodilution
-
Not physiologically driven
-
Few RCTs
-
Unnecessary blood components may be given- Products currently not universally available; shorter shelf life
-
Requires AABB variances and additional cost
Fixed ratio
-
Simple protocols and uniform dosing
-
Easy to administer in prehospital and hospital setting
-
More RCTs, but questionable validity regarding 1:1:1 vs. 1:1:2
-
Blood components readily available
-
Not physiologically driven
-
Unnecessary blood components may be given
-
Does not replenish fibrinogen effectively in early stages
VET-guided BCT
-
Provides early physiologically driven resuscitation
-
Limits blood product waste
-
Blood components readily available
-
Protocols not straight forward; accuracy operator dependent; steep learning curve
-
Cannot be used in prehospital setting
-
Few RCTs
Abbreviations: AABB, American Association of Blood Banks; BCT, blood component therapy; RCT, randomized control trial; VET, viscoelastic test [1,2,3,4,5,6,7,8,9,10,11,14,40,42,46,47,52,54,59,61,69,78,85,86,87,89,94,95,98,99,100,109,115,126].
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Walsh, M.; Moore, E.E.; Moore, H.B.; Thomas, S.; Kwaan, H.C.; Speybroeck, J.; Marsee, M.; Bunch, C.M.; Stillson, J.; Thomas, A.V.; et al. Whole Blood, Fixed Ratio, or Goal-Directed Blood Component Therapy for the Initial Resuscitation of Severely Hemorrhaging Trauma Patients: A Narrative Review. J. Clin. Med. 2021, 10, 320. https://doi.org/10.3390/jcm10020320

AMA Style

Walsh M, Moore EE, Moore HB, Thomas S, Kwaan HC, Speybroeck J, Marsee M, Bunch CM, Stillson J, Thomas AV, et al. Whole Blood, Fixed Ratio, or Goal-Directed Blood Component Therapy for the Initial Resuscitation of Severely Hemorrhaging Trauma Patients: A Narrative Review. Journal of Clinical Medicine. 2021; 10(2):320. https://doi.org/10.3390/jcm10020320

Chicago/Turabian Style

Walsh, Mark, Ernest E. Moore, Hunter B. Moore, Scott Thomas, Hau C. Kwaan, Jacob Speybroeck, Mathew Marsee, Connor M. Bunch, John Stillson, Anthony V. Thomas, and et al. 2021. "Whole Blood, Fixed Ratio, or Goal-Directed Blood Component Therapy for the Initial Resuscitation of Severely Hemorrhaging Trauma Patients: A Narrative Review" Journal of Clinical Medicine 10, no. 2: 320. https://doi.org/10.3390/jcm10020320

APA Style

Walsh, M., Moore, E. E., Moore, H. B., Thomas, S., Kwaan, H. C., Speybroeck, J., Marsee, M., Bunch, C. M., Stillson, J., Thomas, A. V., Grisoli, A., Aversa, J., Fulkerson, D., Vande Lune, S., Sjeklocha, L., & Tran, Q. K. (2021). Whole Blood, Fixed Ratio, or Goal-Directed Blood Component Therapy for the Initial Resuscitation of Severely Hemorrhaging Trauma Patients: A Narrative Review. Journal of Clinical Medicine, 10(2), 320. https://doi.org/10.3390/jcm10020320

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