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The Paradox of Choice in Hemostatic Resuscitation: Still More Options Than Evidence, But a Good Start
SimonStanworthabcdJeannieCallumef
doi : 10.1016/j.tmrv.2021.08.005
Volume 35, Issue 4, October 2021, Pages 71-72
Epidemiology of Massive Transfusion – A Common Intervention in Need of a Definition
Zoe KMcQuiltenabcAndrew WJFlintacdLauraGreenefgBrentonSandersonhiJamesWinearlsjklmErica MWoodab
doi : 10.1016/j.tmrv.2021.08.006
Volume 35, Issue 4, October 2021, Pages 73-79
While massive transfusion (MT) recipients account for a small proportion of all transfused patients, they account for approximately 10% of blood products issued. Furthermore, MT events pose organizational and logistical challenges for health care providers, laboratory and transfusion services. Overall, the majority of MT events are to support major bleeding in surgical patients, trauma and gastrointestinal hemorrhage. The clinical context in which the bleeding event occurred, the number of blood products required, patient age and comorbidities are the most important predictors of outcomes for short- and long-term survival. These data are important to inform blood services, clinicians and health care providers in order to improve care and outcomes for patients with major bleeding. There is no standard accepted definition of MT, with most definitions based on number of blood components administered within a certain time-period or activation of MT protocol. The type of definition used has implications for the clinical characteristics of MT recipients included in epidemiological and interventional studies. In order to understand trends in incidence of MT, variation in blood utilization and patient outcomes, and to harmonize research outcomes, a standard and universally accepted definition of MT is urgently required.
Pathophysiology of Trauma-Induced Coagulopathy
PatriciaDuqueaAlbertoCalvoaChristopherLockieb1HerbertSchöchlb1
doi : 10.1016/j.tmrv.2021.07.004
Volume 35, Issue 4, October 2021, Pages 80-86
There is no standard definition for trauma-induced coagulopathy (TIC). However, it could be defined as an abnormal hemostatic response secondary to trauma. The terms “early TIC” and “late TIC” have been recently suggested. “Early TIC” would refer to the inability to achieve effective hemostasis exacerbating an uncontrolled bleeding in a shocked patient with ischemia-reperfusion damage (bleeding phenotype) and takes place usually early after injury, whereas “late TIC” would represent a hypercoagulable state after surviving a severe tissue injury, that would contribute to thromboembolic events and multiorgan failure (MOF), (thrombotic phenotype), occurring typically hours after the trauma insult though it could be delayed for days. In addition, severe tissue injury when there is no associated shock could be followed by an early hypercoagulable state, representing an evolutionary maladaptive response of a physiologic mechanism created to increase clot formation and prevent bleeding. Therefore, TIC is not a uniform phenotype, ranging from bleeding to pro-thrombotic profiles. This current concept of TIC is mainly based on the recognition of TIC as a unique clotting disorder following trauma in which alterations in the endothelial function, fibrinolysis regulation and platelet behavior after major trauma are the main cornerstones.
Prehospital Tranexamic Acid (TXA) in Patients with Traumatic Brain Injury (TBI)
MarcMaegeleabc
doi : 10.1016/j.tmrv.2021.08.003
Volume 35, Issue 4, October 2021, Pages 87-90
Traumatic brain injury (TBI) remains a significant medical and socioeconomic challenge. The initial injury may be complicated by haemostatic derangements leading to exacerbation of lesions and haemorrhagic progression. The results from the CRASH-3 trial have promoted the implementation of the antifibrinolytic tranexamic acid (TXA) into prehospital Emergency Medical Services (EMS) protocols. Very recently, the efficacy and safety of early out-of-hospital TXA compared to placebo was assessed in patients with moderate or severe TBI in a prospective, multicenter phase II trial, e.g. “The Prehospital TXA for TBI”-trial. Simultaneously, the results from a retrospective analysis of prospectively collected observational data into the Dutch pre-hospital TBI database were published which had assessed whether prehospital administration of TXA may be associated with mortality and functional outcomes in patients with severe TBI. Both studies are reviewed against their limitations and windows of opportunity are highlighted.
The Role of Plasma Transfusion in Pre-Hospital Haemostatic Resuscitation
HarrietTuckeraRossDavenportabLauraGreenabc
doi : 10.1016/j.tmrv.2021.08.004
Volume 35, Issue 4, October 2021, Pages 91-95
Traumatic haemorrhage remains a major cause of preventable death and early haemostatic resuscitation is now a mainstay of treatment internationally. Recently, 2 randomized control trials (RCTs) - PAMPer (Prehospital Air Medical Plasma) and COMBAT (Control of Major Bleeding After Trauma), evaluating the effect of pre-hospital use of plasma on mortality provided conflicting results, raising important questions on the role of plasma resuscitation in pre-hospital environment. Both PAMPer (n = 501 patients) and COMBAT (n = 144 patients) trials were pragmatic RCTs that evaluated the effect of pre-hospital plasma transfusion (two units) versus standard of care on 28/30 days mortality in trauma patients who presented with clinical signs of haemorrhagic shock (defined as hypotension or tachycardia). The PAMPer trial showed that plasma transfusion reduced 30-day mortality compared with standard of care (23% vs 33%, 95% confidence interval -18.6; -1.0%; P = 0.03), while COMBAT trial showed no difference in 28-day survival. The post-hoc analyses of the 2 trials have suggested that the benefit of pre-hospital plasma transfusion may be greater for patients who are coagulopathic, have blunt injury and have a transport time from the scene of injury to the hospital of >20 minutes. In this review we evaluate strengths and limitations of the two trials and their differences and similarities, which may explain the conflicting results, as well as provide directions for future trials to better define the target population that would most benefit from pre-hospital plasma resuscitation. Further, considering the logistical challenges of carrying any blood components on an aircraft, cost/safety of plasma, and the scarcity of universal blood group donors, there is a need for a health economic evaluation of pre-hospital plasma transfusion in trauma patients, prior to this intervention becoming universal.
Roles of Four-Factor Prothrombin Complex Concentrate in the Management of Critical Bleeding
Kenichi A.Tanaka1ShashankShettar1KofiVandyck1Susan M.Shea2EzeldeenAbuelkasem3
doi : 10.1016/j.tmrv.2021.06.007
Volume 35, Issue 4, October 2021, Pages 96-103
Fibrinogen Replacement in Haemostatic Resuscitation: Dose, Laboratory Targets and Product Choice
NicolaCurry
doi : 10.1016/j.tmrv.2021.06.005
Volume 35, Issue 4, October 2021, Pages 104-107
Fibrinogen is a key coagulation protein that is necessary for the formation of stable clots. Fibrinogen levels have been reported to be one of the first to fall during major haemorrhage reflecting consumption, dilution and fibrinogenolysis. Its role in acquired major haemorrhage, both in relation to the contribution it plays to the coagulopathy of major bleeding that can exacerbate bleeding and how effective fibrinogen supplementation can be at improving clinical outcomes, has received a great deal of attention over the last 10 - 15 years. This commentary focuses on just three of the more recent publications from the last 5 years that provide some of the evidence behind how we can think about fibrinogen as a haemostatic treatment for acquired major haemorrhage and how we can use the laboratory thresholds to guide therapy.
Viscoelastic Testing in Traumatic Brain Injury: Key Research Insights
Taylor N.AndersonaMartin A.SchreiberbSusan E.Rowellc
doi : 10.1016/j.tmrv.2021.08.002
Volume 35, Issue 4, October 2021, Pages 108-112
The role of viscoelastic testing in the evaluation and management of traumatic brain injury (TBI) remains a subject of ongoing exploration. This review highlights four key publications that provide significant insights into this subject. Holcomb et al. provided early evidence of the relationship between thromboelastography (TEG) and conventional coagulation tests (CCTs). Later, Samuels et al. used TEG to identify a unique coagulopathy phenotype in TBI characterized by a notable absence of fibrinolytic abnormalities. Dixon et al. built upon these findings by exploring the application of TEG in the context of antifibrinolytic administration, noting a similar lack of effect on LY30. Finally, Guillotte et al. demonstrated the utility of TEG-PM in assessing platelet dysfunction in TBI. While these studies provide key early support for the utility of viscoelastic testing in the TBI, further exploration is needed to define evidence-based guidelines for clinical application.
Hemostatic Resuscitation in Children
Rafael G.Ramos-JimenezaChristineLeeperab1
doi : 10.1016/j.tmrv.2021.06.008
Volume 35, Issue 4, October 2021, Pages 113-117
Trauma is a major source of morbidity and mortality for children worldwide; life-threatening hemorrhage is a primary cause of preventable death. Essential interventions in children with life-threatening hemorrhage include hemostatic resuscitation and mechanical control of bleeding. Herein we review pediatric hemostatic resuscitation, a strategy that addresses both hemorrhagic shock and the coagulopathic complications described in patients with major hemorrhage. Some components of hemostatic resuscitation may include: early and aggressive resuscitation with blood products, minimizing crystalloid and hemodilution, antifibrinolytic adjuncts such as tranexamic acid, and the novel use of low-titer group O whole-blood (LTOWB) transfusion in injured children. The following selection of important publications address the current state of hemostatic resuscitation strategies in pediatric trauma patients as well as the remaining knowledge gaps and areas for further research.
Risk of ABO-Incompatible Plasma From Non-ABO-Identical Components
Kristen N.Ruby12Sarah K.Harm34Nancy M.Dunbar12
doi : 10.1016/j.tmrv.2021.06.006
Volume 35, Issue 4, October 2021, Pages 118-122
The last several decades have seen significant changes in the approach to resuscitation of bleeding patients. These include the adoption of ABO-incompatible plasma transfusion in the form of group A plasma and/or low titer group O whole blood for trauma patients of unknown ABO group. Studies to date have examined the impact of these practices on patient outcomes and clinical markers of hemolysis in recipients of ABO-incompatible plasma compared to those for whom the plasma is ABO-compatible. Risk for increased mortality and/or overt hemolysis appear to be low among recipients of ABO-incompatible plasma; however, nearly all of studies are retrospective and most have focused only on adult trauma patients so results may not be generalizable to other bleeding patients. Work continues to evaluate the role of various titer thresholds in decreasing hemolytic risk and opportunities remain to improve our understanding of anti-A and anti-B antibody interactions with complement/endothelium and identify strategies to minimize risk.
