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Abstract

  1. Top of page
  2. Abstract
  3. PATHOPHYSIOLOGY OF THE COAGULATION DISTURBANCE IN MASSIVE HEMORRHAGE
  4. RESUSCITATION WITH RATIO-BASED PLASMA INFUSION
  5. ALTERNATIVE (AND ADJUNCTIVE) STRATEGIES TO RATIO-BASED PLASMA INFUSIONS
  6. THE IMPORTANCE OF HAVING A PROTOCOL TO OPTIMIZE COMMUNICATION AND COORDINATION OF CARE
  7. CONCLUSION
  8. CONFLICT OF INTEREST
  9. REFERENCES

The following review will detail the current knowledge in massive hemorrhage with regard to the pathophysiology of the coagulation disturbance, the role of plasma, the role of alternatives to plasma, and the clinical value of having a massive transfusion protocol. The coagulation disturbance in trauma patients is more than just the result of consumption of clotting factors at sites of injury and dilution from the infusion of intravenous fluids and red blood cells (RBCs). Even before substantial amounts of fluid resuscitation and RBC transfusion, one-quarter of trauma patients already have abnormal coagulation variables. There is an apparent role for the activation of protein C, hypofibrinogenemia, and fibrin(gen)olysis in the coagulation disturbance after trauma and massive hemorrhage. None of these three disturbances would be completely mitigated by the use of plasma alone, suggesting that there may be an opportunity to improve care of these patients with alternative strategies, such as fibrinogen concentrates and antifibrinolytics. Despite numerous retrospective cohort studies evaluating 1:1 plasma to RBC formula–driven resuscitation, the overall clinical value of this approach is unclear. Studies have even raised concerns regarding a potential increase in morbidity associated with this approach, particularly for patients overtriaged to 1:1 where a massive transfusion is unlikely. We also do not have sufficient evidence to recommend either goal-directed therapy with thromboelastography or early use of fibrinogen replacement, with either cryoprecipitate or fibrinogen concentrates. We have high-quality data that argue against the role for recombinant Factor VIIa that should prompt removal of this strategy from existing protocols. In contrast, we have high-level evidence that all bleeding trauma patients should receive tranexamic acid as soon as possible after injury. This therapy must be included in hemorrhage protocols. If we are to improve the care of massively bleeding patients on a firm scientific ground, we will need large-scale randomized trials to delineate the role of coagulation replacement and the utility of laboratory monitoring. But even until these trials are completed, it is clear that a massive transfusion protocol is needed in all hospitals that manage bleeding patients, to ensure a prompt and coordinated response to hemorrhage.

ABBREVIATIONS:
DIC =

disseminated intravascular coagulopathy

PAI =

plasminogen activator inhibitor

PCC(s) =

prothrombin complex concentrate(s)

In the past 5 years, we have been inundated with a substantial number of reports on the management of massive hemorrhage, particularly in the setting of military and civilian trauma. We have progressed substantially in our understanding of the pathophysiology of the coagulopathy associated with traumatic injury, particularly in regard to an important role of activated protein C, hypofibrinogenemia, and fibrin(gen)olysis derived from recent data. Nonetheless, with the exception of the clear utility of tranexamic acid in trauma patients, we are no further ahead in our understanding of the role of plasma and coagulation concentrates due to the poor quality of the data available in the literature. The following review will detail the current knowledge in this area with regard to the pathophysiology of the coagulation disturbance, the role of plasma, the role of alternatives to plasma, and the clinical value of having a massive transfusion protocol.

PATHOPHYSIOLOGY OF THE COAGULATION DISTURBANCE IN MASSIVE HEMORRHAGE

  1. Top of page
  2. Abstract
  3. PATHOPHYSIOLOGY OF THE COAGULATION DISTURBANCE IN MASSIVE HEMORRHAGE
  4. RESUSCITATION WITH RATIO-BASED PLASMA INFUSION
  5. ALTERNATIVE (AND ADJUNCTIVE) STRATEGIES TO RATIO-BASED PLASMA INFUSIONS
  6. THE IMPORTANCE OF HAVING A PROTOCOL TO OPTIMIZE COMMUNICATION AND COORDINATION OF CARE
  7. CONCLUSION
  8. CONFLICT OF INTEREST
  9. REFERENCES

It is clear that in the past decade, we have come to realize that the coagulation disturbance in trauma patients is more than just the result of consumption of clotting factors at sites of injury and dilution from the infusion of intravenous (IV) fluids and red blood cells (RBCs). Hence, it is clear that the infusion of plasma alone in the management of severely injured trauma patients with coagulopathic-type bleeding is likely to be insufficient to achieve hemostasis. The known coagulation disturbances and their potential treatments in massive hemorrhage are detailed in Table 1. It is extremely likely that throughout resuscitation of the massively bleeding patient, the predominant mechanism for coagulopathy may change over time as a result of therapy and/or the hemostatic response to injury. Hence, for us to truly understand this process, we will need serial measurements throughout resuscitation to fully understand what is happening to the coagulation variables of the massively bleeding patient. It is also true that therapy will need to be individualized—patients with differing injuries and at different points in the resuscitation process will need different therapies.

Table 1. The implicated pathophysiologic reasons for coagulation disturbances in massively bleeding patients and potential therapies for each mechanism
MechanismsDetailsPotential therapy
Consumption of clotting factorsAt sites of injuryPlasma
Dilution from IV fluidsBy infusion of clotting factor deficient products during resuscitationRestrictive use of crystalloids and colloids; plasma
HypothermiaImpairment of thrombin generation1,2 and fibrinogen synthesis3Aggressive rewarming and preventative strategies
Metabolic acidosisImpairment of thrombin generation1,2 and increased degradation of fibrinogen4Maintaining adequate perfusion
Activation of protein CImpaired clot generation (proteolytic inhibition of FV and FVIII) and fibrinolysis (via depletion of PAI-1 and uncontrolled tissue plasminogen activator)Antifibrinolytics; plasma to replace depleted protein C inhibitor; fibrinogen replacement with cryoprecipitate or fibrinogen concentrates
Hyperfibrin(ogen)olysisFibrin and fibrinogen depletionAntifibrinolytics; fibrinogen replacement with cryoprecipitate or fibrinogen concentrates

In 2003, Brohi and colleagues5 analyzed a cohort of 1088 trauma patients transported to hospital by helicopter and found that 24% had a coagulopathy (defined as a prothrombin time of >18 sec, an activated partial thromboplastin time of >60 sec, or a thrombin time of >15 sec). Patients presenting with these abnormal laboratory test results had a higher rate of death (46% vs. 11%, p < 0.001). This study was the first to raise suspicion that the hemodilution was not the cause of the coagulopathy since one-quarter of patients already had a coagulation disturbance before the first unit of blood. In addition, they found no association between the volume of fluid administered and the development of abnormal coagulation test results. The incidence of coagulopathy was strongly associated with the injury severity score, suggesting that the degree of tissue injury and/or hypoperfusion may be causative factors in this process. These findings support development of coagulopathy in some patients before therapeutic intervention.

Several studies have confirmed that severely injured trauma patients have activation of the protein C pathway as shown in Fig. 1 resulting in an “anticoagulant” effect.6-8 A prospective cohort study of 203 major trauma patients found that patients with tissue hypoperfusion and severe injury had activation of protein C, with subsequent inactivation of Factor (F)V and FVIII and derepression of fibrinolysis.8 Protein C is activated by thrombin, thrombomodulin, and endothelial protein C receptor. Hypoperfusion is believed to result in increased expression of thrombomodulin on the surface of endothelial cells. The thrombomodulin binds thrombin and the complex activates protein C. Hence, thrombin starts acting as an anticoagulant, rather than assisting with forming a fibrin clot to stop the bleeding. Activated protein C proteolytically inactivates FV and FVIII resulting in impairment in clot generation. In addition, activated protein C depletes plasminogen activator inhibitor (PAI-1). Depletion of PAI-1 results in unrestrained tissue plasminogen activator, resulting in plasmin generation and clot lysis (fibrinolysis). In addition, plasmin is able to degrade fibrinogen (fibrinogenolysis), further depleting the fibrinogen reserves. Hence, activated protein C has numerous deleterious effects on the coagulation system in a bleeding patient—inactivation of FV and FVIII, depletion of fibrinogen, and clot lysis due to hyperfibinolysis. The combined effects of these lead to impaired clot formation (Fig. 1).

image

Figure 1. Pathophysiology of trauma-induced activation of protein C.

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Fibrinogen has recently been recognized to be a critical factor in the bleeding patient, participating in both primary hemostasis (via bridging between platelets [PLTs] via glycoprotein IIb/IIIa) and secondary hemostasis (fibrin formation). More than 15 years ago, Hiippala and colleagues9 showed that fibrinogen was the first factor to reach a set “critical level” (<1.0 g/L) at 142% of total blood volume loss compared to PLTs dropping below a critical level (50 × 109/L) at 230% of total blood volume loss. The fibrinogen level is thought to decrease rapidly in severely injured trauma patients due to consumption, dilution, minimal total body reserves of fibrinogen (10 g in an average adult), and hyperfibrinolysis. The prominent decrease in fibrinogen levels after injury has also been confirmed in animal hemorrhage models.10-12 These studies have led investigators to evaluate fibrinogen concentrates in the management of severely injured trauma patients.13

Hyperfibrinolysis also becomes increasingly more common as the injury severity score increases in patients with severe blunt trauma.14 Variable incidence of hyperfibrinolysis in trauma patients has been reported. When measured by thromboelastography in a cohort of 161 trauma patients the incidence was only 2.5%, but with an associated mortality rate of 67%.15 Similarly in a study of 334 major trauma patients, hyperfibrinolysis was observed in 6.8% of patients, with a mortality rate of 86%.16 The lethality of hyperfibrinolysis emphasizes the importance of early recognition of this entity and the importance of early administration of antifibrinolytic drugs. Some investigators have also endorsed the use of fibrinogen replacement for the management of hyperfibrinolysis.17

Hypothermia and acidosis also have detrimental effects on thrombin generation, fibrinogen synthesis, and fibrinogen degradation as listed in Table 1. In contrast, there is little evidence to support the hypothesis that massively bleeding patients have disseminated intravascular coagulopathy (DIC). In a series of 423 trauma patients, 11% met the criteria for DIC, but pathology review of 40 organs and 27 autopsies from these patients revealed that none had pathologic evidence of DIC.18 The lack of DIC in severely injured trauma patients was also confirmed in a series of 80 patients from Denmark.19 A triad of hypothermia, acidosis, and coagulopathy is associated with high mortality in trauma victims.

RESUSCITATION WITH RATIO-BASED PLASMA INFUSION

  1. Top of page
  2. Abstract
  3. PATHOPHYSIOLOGY OF THE COAGULATION DISTURBANCE IN MASSIVE HEMORRHAGE
  4. RESUSCITATION WITH RATIO-BASED PLASMA INFUSION
  5. ALTERNATIVE (AND ADJUNCTIVE) STRATEGIES TO RATIO-BASED PLASMA INFUSIONS
  6. THE IMPORTANCE OF HAVING A PROTOCOL TO OPTIMIZE COMMUNICATION AND COORDINATION OF CARE
  7. CONCLUSION
  8. CONFLICT OF INTEREST
  9. REFERENCES

In 2007 and 2008, Borgman and coworkers20 and Spinella and coworkers21 published two articles detailing the remarkable beneficial effect of high ratios of plasma to RBCs on the mortality of injured patients in Iraq. They concluded that the use of high ratios resulted in an absolute risk reduction in mortality of 55% and would assist with the cessation of hemorrhage and hence a reduction in the need for RBC transfusion. Based on these data, the US Army Surgeon General distributed a policy recommending adoption of 1:1 plasma to RBC ratio for all military patients with significant trauma at risk for requiring a massive transfusion. These two articles were retrospective in nature, with expected differences in the baseline characteristics between patients receiving high and low ratio plasma therapy. Patients were not managed with immediately available thawed plasma, and hence both studies were affected by survivorship bias. Because plasma has a processing and transport time of approximately 93 minutes22 until commencement of infusion after arrival to hospital, nonsurvivors are more likely to die without having the opportunity to receive plasma. Hence these patients likely died with a low ratio of plasma to RBCs, rather than because of the low ratio.

These two articles were followed by a flurry of civilian studies that analyzed the ratio at 24 hours (or ratio at the time of death for those that died before 24 hr) and came to similar conclusions about the benefit of 1:1 resuscitation. Snyder and colleagues22 were the first to provide evidence that these articles were likely observing survivorship bias, rather than a true beneficial effect of plasma. Rajasekhar and coworkers23 subsequently published a systematic review on this topic, including 11 studies (three prospective, seven retrospective, and one case-control). The authors concluded that there was insufficient evidence to support the use of fixed ratios in massively transfused trauma patients. They noted numerous limitations to the study design of these 11 studies including survivorship bias, heterogeneous patient populations, limited reporting of baseline variables, inconsistent massive transfusion protocols, and lack of documentation of other rescue therapies (e.g., recombinant FVIIa). This publication comes at a time when formula-driven resuscitation has already been incorporated into the standard of care at many, if not most, trauma centers. Nonrandomized trials will not provide us with the definitive answer to this important question. Large, randomized, multicenter studies will be required. Two trials are under way to assist with answering this question, the Trauma Lab versus Formula pilot trial (TR-FL)24 and the Prospective Randomized Optimum Platelet and Plasma Ratios (PROPPR) trial.

The US Army was the first to change practice and commence managing patients with thawed plasma at arrival to hospital. In 2010, they reported on 777 massively transfused trauma patients cared for before and after implementation of 1:1.25 Despite clear adoption of the protocol, there was no mortality benefit observed. In addition, despite receiving a median of 6 additional units of plasma and one additional apheresis PLT transfusion, the use of RBCs actually increased, providing no evidence that this therapy provided hemostatic benefit.

Researchers have also raised concerns about the collateral damage of 1:1 protocols.26-29 Two issues have been raised. One, overtriage to 1:1 will result in patients receiving plasma when they need none. Two, for patients who are massively transfused, the extra plasma will result in complications of fluid overload (edema, abdominal compartment syndrome, respiratory compromise) and will increase the risk of multiple organ failure. A report of 1716 nonmassively transfused trauma patients compared patients managed with 1:1 compared to no plasma.29 Plasma administration was associated with a substantial increase in complications, particularly adult respiratory distress syndrome, without improvement in survival. This was confirmed in a study of 1788 nonmassively transfused trauma patients.28 Patients receiving a high ratio of fresh-frozen plasma to RBCs had an increase in respiratory morbidity and the authors recommended rapid termination of 1:1 when it becomes clear that a massive transfusion will not be required. The increase in multiple organ failure with plasma is in addition to the major risks associated with plasma, including transfusion-related acute lung injury (TRALI), transfusion-associated circulatory overload, and anaphylaxis. The risk of TRALI is approximately 1 in 5000,30 which has been somewhat mitigated by the implementation of predominantly male plasma, with most countries reporting a 50% reduction in cases reported to hemovigilance systems.31 This reduced risk may not be seen in massively transfused patients who receive predominantly group AB plasma until the patient's native ABO blood group is known. Due to the high demand for AB plasma, many blood suppliers have been unable to achieve 100% male plasma for this particular ABO blood group.

ALTERNATIVE (AND ADJUNCTIVE) STRATEGIES TO RATIO-BASED PLASMA INFUSIONS

  1. Top of page
  2. Abstract
  3. PATHOPHYSIOLOGY OF THE COAGULATION DISTURBANCE IN MASSIVE HEMORRHAGE
  4. RESUSCITATION WITH RATIO-BASED PLASMA INFUSION
  5. ALTERNATIVE (AND ADJUNCTIVE) STRATEGIES TO RATIO-BASED PLASMA INFUSIONS
  6. THE IMPORTANCE OF HAVING A PROTOCOL TO OPTIMIZE COMMUNICATION AND COORDINATION OF CARE
  7. CONCLUSION
  8. CONFLICT OF INTEREST
  9. REFERENCES

Numerous alternative or adjunctive strategies have been studied in this patient population, including but not limited to antifibrinolytics, resuscitation with coagulation concentrates, and goal-directed individualized care based on laboratory coagulation assessment. The use of recombinant FVIIa will not be discussed in this review due to the lack of benefit seen in clinical trials (including trauma)32,33 and clear evidence of harm.34,35 All of these strategies, including 1:1 resuscitation, are not mutually exclusive and likely all should be potential components of a massive hemorrhage protocol. Of note, some review articles on 1:1 have cited that one of the benefits of the 1:1 approach is that laboratory monitoring of the coagulation variables is no longer necessary. It is premature to come to this conclusion until we have studies documenting the safety of “blind” transfusion without laboratory monitoring. Frequent laboratory monitoring is required as long as the patient continues to hemorrhage.

We have outstanding evidence for the use of tranexamic acid for all trauma patients presenting with significant hemorrhage (systolic blood pressure less than 90 mmHg or heart rate over 110 beats/min).36 The CRASH-2 trial randomized over 20,000 patients to either tranexamic acid or placebo. Tranexamic acid reduces the risk of death (odds ratio [OR], 0.91; 95% confidence interval [CI], 0.85-0.97; p = 0.0035) and death from hemorrhage (OR, 0.85; 95% CI, 0.76-0.96; p = 0.0077). It was of greatest mortality benefit if administered within the first hour of injury (OR, 0.68; 95% CI, 0.57-0.82; p < 0.001). Despite its antifibrinolytic effect, there was no increased risk of thromboembolic complications. Certainly, any patient bleeding sufficiently to get RBC and plasma transfusions should receive a loading dose and infusion of tranexamic acid, commenced immediately on arrival to hospital. The results of the CRASH-2 study were confirmed in an analysis of 896 consecutive UK and US military trauma admissions, of whom 293 had received tranexamic acid.37 The tranexamic acid cohort had a lower mortality rate (17.4% vs. 23.9%, p = 0.03) despite having a higher injury severity score (25.2 vs. 22.5, p < 0.001).

The latter two adjunctive strategies, resuscitation with coagulation concentrates and goal-directed individualized care based on laboratory coagulation assessment, will be discussed together as the majority of publications describe the use of thromboelastography to guide the use of fibrinogen and other coagulation concentrates. A Cochrane systematic review of nine studies involving 776 patients concluded that there was an absence of evidence that thromboelastography reduced morbidity or mortality in massively bleeding patients.38 In addition, a systematic review of plasma and fibrinogen concentrates concluded that there was insufficient evidence for the therapeutic value of plasma.39 The authors detail numerous fibrinogen studies, although none were randomized, controlled trials in the setting of trauma. Of the three included randomized trials in nontrauma patients, two were in the setting of cardiac surgery (one adult and one pediatric trial) and the other was in urologic surgery. The largest of these three trials included only 31 patients. Clearly, we do not have sufficiently designed randomized clinical trials to determine if fibrinogen concentrates are an effective hemostatic agent in the setting of massive hemorrhage.

The highest-quality report on the use of fibrinogen concentrates in trauma, although nonrandomized, has been published by Schochl and colleagues.40 They compared 80 patients managed at the Salzburg trauma center (managed with fibrinogen concentrates and prothrombin complex concentrates [PCCs] based on thromboelastography) to 601 patients included in the German trauma registry (managed with the standard plasma approach). Not surprisingly, due to the lack of randomization, there were numerous baseline differences between the two cohorts. The injury severity scores were, however, similar (35 for both groups). The fibrinogen-PCC group avoided RBC transfusion 29% of the time, compared to only 3% in the German plasma cohort. Whether this is due to its impressive hemostatic effects, or less hemodilution, is not known. The mortality rate was comparable (7.5% in the fibrinogen-PCC group and 10.0% in the plasma group, p = 0.69). We need a large, randomized trial comparing the standard plasma approach to goal-directed, thromboelastography-guided concentrate therapy before it can be recommended as a standard approach. There are numerous benefits to the “concentrate” approach: faster to prepare these products (not frozen and no ABO group required), smaller volume (less hemodilution), and potentially fewer transfusion reactions (most notably, TRALI).

To further muddy the waters, we do not know the level at which hypofibrinogenemia contributes to hemorrhage. A study from 1987, including 36 massively transfused patients (managed with modified whole blood—RBCs in cryosupernatant), concluded that coagulopathic-type bleeding was not observed until the fibrinogen level dropped below 1.0 g/L.41 The study included few patients, with only 14 of 36 patients having a fibrinogen level of less than 1.0 g/L. This is the study that has been repeatedly cited as the scientific basis for this cutoff. This threshold has recently been called into question, with some recommending a cutoff of 1.5 to 2.0 g/L.42,43 A study in patients undergoing cardiac surgery found that a low normal preoperative baseline fibrinogen, even when within the normal range, increased the risk of postoperative transfusion.44 In addition, in the setting of postpartum hemorrhage a fibrinogen below 2.0 g/L at the commencement of bleeding increased the risk of severe postpartum hemorrhage.45 We need to question this threshold of 1.0 g/L in the massively bleeding patient. We currently have no idea where the fibrinogen needs to be when managing a patient with marked blood loss. Further clinical studies are needed to determine optimal fibrinogen levels in trauma resuscitation.

THE IMPORTANCE OF HAVING A PROTOCOL TO OPTIMIZE COMMUNICATION AND COORDINATION OF CARE

  1. Top of page
  2. Abstract
  3. PATHOPHYSIOLOGY OF THE COAGULATION DISTURBANCE IN MASSIVE HEMORRHAGE
  4. RESUSCITATION WITH RATIO-BASED PLASMA INFUSION
  5. ALTERNATIVE (AND ADJUNCTIVE) STRATEGIES TO RATIO-BASED PLASMA INFUSIONS
  6. THE IMPORTANCE OF HAVING A PROTOCOL TO OPTIMIZE COMMUNICATION AND COORDINATION OF CARE
  7. CONCLUSION
  8. CONFLICT OF INTEREST
  9. REFERENCES

The importance of the coordination of care for the massively bleeding patient cannot be overstated. Nunez and coworkers46 published a comprehensive review of the steps required to build, implement, and monitor a massive transfusion protocol. A survey published in 2006 found that massive transfusion protocols existed at only a small number of trauma centers in the United States.47 A US survey published 4 years later found that massive transfusion protocols were in place in 85% of institutions.48 Overall, 65% of these protocols had been implemented in the past 5 years, suggesting that before this point most of the approach to the massively bleeding patient was ad hoc. They also found considerable heterogeneity in the transfusion approach across these centers, likely due to the lack of high-quality data to support one approach over another. The military has been able to show that the implementation of clinical practice guidelines for massive transfusion can change care.25 In their review of 777 military patients, they were able to show an improvement in the temperature of patients on arrival, a reduction in crystalloid exposure, and an excellent compliance with their 1:1 protocol. In a review of 125 massive transfusion protocol activations, Cotton and coworkers49 found poor compliance (27% for all measures of performance). Full compliance was associated with an improvement in survival (87% vs. 45%, p < 0.001). Compliance may be a measure of better care by the clinical team, or it may simply reflect that it is easier to be compliant with the protocol with a less unstable patient, who by definition has a better chance of survival.

We need to be concerned about the knowledge of physicians involved in managing these patients after the publication of a questionnaire given to 32 emergency physicians from 11 hospitals in the United Kingdom.50 Physicians from seven different institutions answered that their hospital had a massive transfusion protocol, although three other physicians from the same hospitals stated that their hospital did not have such a protocol. In truth, only four of the 11 hospitals had a massive transfusion protocol on further investigation. Overall, 16% knew the definition for massive transfusion, 3% knew fibrinogen was a component of both plasma and cryoprecipitate, and a remarkable 78% thought that the risk of an acute hemolytic reaction from uncrossmatched blood was in excess of 5% (correct answer, <0.5%). Despite the flurry of publications in the past 5 years regarding the transfusion management of patients with massive hemorrhage, it appears an inadequate amount of knowledge is reaching the clinicians at the front line.

CONCLUSION

  1. Top of page
  2. Abstract
  3. PATHOPHYSIOLOGY OF THE COAGULATION DISTURBANCE IN MASSIVE HEMORRHAGE
  4. RESUSCITATION WITH RATIO-BASED PLASMA INFUSION
  5. ALTERNATIVE (AND ADJUNCTIVE) STRATEGIES TO RATIO-BASED PLASMA INFUSIONS
  6. THE IMPORTANCE OF HAVING A PROTOCOL TO OPTIMIZE COMMUNICATION AND COORDINATION OF CARE
  7. CONCLUSION
  8. CONFLICT OF INTEREST
  9. REFERENCES

We are not much further ahead in our understanding of when and how much plasma to give a massively bleeding patient. But we are substantially further ahead in our understanding of the pathophysiology of trauma-associated coagulopathy. We know that administering antifibrinolytics is lifesaving. Over the next decade we have much to clarify if we are going to improve outcomes for massively bleeding patients. We need to better understand which coagulation factors are needed, how much to give, when to administer them, and for which types of patients. We need to understand if thromboelastography will help to optimally direct transfusion management to improve patient outcomes. We also need to urgently clarify the role of plasma. The strategy in many trauma centers worldwide is to give massive amounts of plasma, often unguided by laboratory metrics. Given that plasma can have serious, and sometimes fatal, adverse consequences and that such use puts considerable strain on the blood suppliers, we need to verify that this strategy is in the best interests of our patients. It is almost certainly likely that patients with different types of injuries, at different points in their resuscitation, will need different transfusion strategies. Hence, we will likely need high-tech, frequent laboratory testing, in conjunction with some “blind” coagulation replacement for those patients with extremely rapid bleeding. It would be naïve to think that we could get away with “one protocol fits all.” A consensus conference on massive transfusion,51 organized by the National Advisory Committee on Blood and Blood Products (Canada), provides a detailed list of recommendations for assisting with the development of an institutional massive hemorrhage policy. This document also highlights some of the unanswered questions to give the transfusion medicine and trauma physicians some guidance on where we need to go from here.

REFERENCES

  1. Top of page
  2. Abstract
  3. PATHOPHYSIOLOGY OF THE COAGULATION DISTURBANCE IN MASSIVE HEMORRHAGE
  4. RESUSCITATION WITH RATIO-BASED PLASMA INFUSION
  5. ALTERNATIVE (AND ADJUNCTIVE) STRATEGIES TO RATIO-BASED PLASMA INFUSIONS
  6. THE IMPORTANCE OF HAVING A PROTOCOL TO OPTIMIZE COMMUNICATION AND COORDINATION OF CARE
  7. CONCLUSION
  8. CONFLICT OF INTEREST
  9. REFERENCES
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  • 2
    Martini WZ, Pusateri AE, Uscilowicz JM, Delgado AV, Holcomb JB. Independent contributions of hypothermia and acidosis to coagulopathy in swine. J Trauma 2005;58:1002-9; discussion 1009-10.
  • 3
    Martini WZ. The effects of hypothermia on fibrinogen metabolism and coagulation function in swine. Metabolism 2007;56:214-21.
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    Martini WZ, Holcomb JB. Acidosis and coagulopathy: the differential effects on fibrinogen synthesis and breakdown in pigs. Ann Surg 2007;246:831-5.
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    Brohi K, Singh J, Heron M, Coats T. Acute traumatic coagulopathy. J Trauma 2003;54:1127-30.
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    Cohen MJ, Brohi K, Ganter MT, Manley GT, Mackersie RC, Pittet JF. Early coagulopathy after traumatic brain injury: the role of hypoperfusion and the protein C pathway. J Trauma 2007;63:1254-61; discussion 1261-2.
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    Martini WZ, Chinkes DL, Sondeen J, Dubick MA. Effects of hemorrhage and lactated Ringer's resuscitation on coagulation and fibrinogen metabolism in swine. Shock 2006;26:396-401.
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    Nienaber U, Innerhofer P, Westermann I, Schöchl H, Attal R, Breitkopf R, Maegele M. The impact of fresh frozen plasma versus coagulation factor concentrates on morbidity and mortality in trauma-associated haemorrhage and massive transfusion. Injury 2011;42:697-701.
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    Schochl H, Frietsch T, Pavelka M, Jambor C. Hyperfibrinolysis after major trauma: differential diagnosis of lysis patterns and prognostic value of thrombelastometry. J Trauma 2009;67:125-31.
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    Carroll RC, Craft RM, Langdon RJ, Clanton CR, Snider CC, Wellons DD, Dakin PA, Lawson CM, Enderson BL, Kurek SJ. Early evaluation of acute traumatic coagulopathy by thrombelastography. Transl Res 2009;154:34-9.
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    Tauber H, Innerhofer P, Breitkopf R, Westermann I, Beer R, El Attal R, Strasak A, Mittermayr M. Prevalence and impact of abnormal ROTEM(R) assays in severe blunt trauma: results of the “Diagnosis and Treatment of Trauma-Induced Coagulopathy (DIA-TRE-TIC) study.” Br J Anaesth 2011;107:378-87.
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    Schochl H, Voelckel W, Maegele M, Solomon C. Trauma-associated hyperfibrinolysis. Hamostaseologie 2011;32:22-7.
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    Rizoli S, Nascimento B Jr, Key N, Tien HC, Muraca S, Pinto R, Khalifa M, Plotkin A, Callum J. Disseminated intravascular coagulopathy in the first 24 hours after trauma: the association between ISTH score and anatomopathologic evidence. J Trauma 2011;71 Suppl 1:S441-7.
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    Johansson PI, Sorensen AM, Perner A, Welling KL, Wanscher M, Larsen CF, Ostrowski SR. Disseminated intravascular coagulation or acute coagulopathy of trauma shock early after trauma? A prospective observational study. Crit Care 2011;15:R272.
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    Borgman MA, Spinella PC, Perkins JG, Grathwohl KW, Repine T, Beekley AC, Sebesta J, Jenkins D, Wade CE, Holcomb JB. The ratio of blood products transfused affects mortality in patients receiving massive transfusions at a combat support hospital. J Trauma 2007;63:805-13.
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    Spinella PC, Perkins JG, Grathwohl KW, Beekley AC, Niles SE, McLaughlin DF, Wade CE, Holcomb JB. Effect of plasma and red blood cell transfusions on survival in patients with combat related traumatic injuries. J Trauma 2008;64 Suppl:S69-77; discussion S77-8.
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