A clinical review of bleeding dilemmas in trauma

doi:10.1053/j.seminhematol.2003.11.009

Seminars in Hematology

Volume 41, Supplement 1, January 2004, Pages 40-43

https://doi.org/10.1053/j.seminhematol.2003.11.009 Get rights and content

Abstract

Trauma is rapidly replacing stroke and cardiovascular disease as a leading cause of death in Western countries such as the United States, and almost a third (30%) of trauma deaths are due to blood loss. Although the new intervention strategies that have been developed and adopted by emergency care staff have reduced this mortality in recent years, bleeding continues to be a major challenge in the management of trauma patients. This paper reviews recent developments and controversies in trauma care, and, in particular, the potential role of procoagulant therapy using recombinant factor VIIa in the prevention of mortality due to bleeding.

Section snippets

The changing role of fluid resuscitation

Until the 1990s, the standard intervention for hypotensive trauma patients was aggressive fluid resuscitation with the goal of restoring end-organ perfusion and oxygen delivery prior to surgery. Increase in circulating volume also increases cardiac output and blood pressure. However, it was suggested as early as 19206 that a sudden increase in blood pressure may prove detrimental since it has the potential to precipitate rebleeding from sites where physiological mechanisms have brought about

Potential roles of procoagulant therapy

Although there are limited data on the use of rFVIIa in the acute management of trauma patients, procoagulant intervention offers some intriguing potential benefits. It appears likely that rFVIIa could potentially play an important future role in reducing fatalities due to hemorrhage following trauma. A hypotensive patient reaching hospital has already lost about a third of their blood volume and will die after losing about 800 mL more blood. Thus, any intervention that limits blood loss at an

Conclusions

•
Targeted hypotensive resuscitation may offer better survival than aggressive fluid resuscitation.
•
Maintaining stability of primary hemostasis at the site of injury that limits bleeding is an important consideration in the acute management of trauma patients.
•
New interventions such as procoagulant therapy using rFVIIa are likely to become important elements in preventing mortality due to bleeding following trauma.
•
Further trials are needed to explore the potential benefits of procoagulant

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Cited by (80)

Concomitant severe traumatic brain injury is not associated with increased red blood cell transfusion volumes in patients with pelvic fractures: A retrospective observational study
2024, Injury
Traumatic brain injury (TBI)-associated coagulopathy significantly influences survival outcomes in patients with multiple injuries. Severe TBI can potentially affect systemic hemostasis due to coagulopathy; however, there is limited evidence regarding whether the risk of hemorrhage increases in patients with pelvic fractures complicated with TBI. Therefore, through multivariable analysis, we aimed to examine the association between severe TBI and increased blood transfusion requirements in patients with pelvic fractures.
This retrospective observational study was conducted at a tertiary care facility in Japan. Patients aged 16 years or older with pelvic fractures who were admitted to our intensive care unit between April 2014 and December 2021 were included in the analysis. The patients were categorized into no to mild and severe TBI groups according to whether the Head Abbreviated Injury Scale (AIS) score was 3 or higher. The primary outcome was the number of red blood cell (RBC) units transfused within 24 h after arrival at the hospital. The primary outcome was analyzed using univariable and multivariable linear regression analyses. The covariates used for the multivariable linear regression analysis were age, sex, antithrombotic therapy, mechanism of injury, Pelvic AIS score, and extravasation on contrast-enhanced computed tomography on admission.
We identified 315 eligible patients (221 and 94 in the no to mild and severe TBI groups, respectively). In the univariable analysis, the RBC transfusion volume within 24 h after arrival was significantly higher in the severe TBI group than in the no to mild TBI group (2.53-unit increase; 95 % confidence interval [CI]: 0.46–4.61). However, in the multivariable analysis, no statistically significant association was detected between severe TBI and the RBC transfusion volume within 24 h after arrival at the hospital (0.87-unit increase; 95 % CI: −1.11–2.85).
Concomitant severe TBI was not associated with increased RBC transfusion volumes in patients with pelvic fractures on multivariable analysis.
Coagulopathy and haemorrhagic progression in traumatic brain injury: advances in mechanisms, diagnosis, and management
2017, The Lancet Neurology
Citation Excerpt :
The prevalence of coagulopathy in TBI at admission to hospital ranges from 7%14 to 63%,16 reflecting the wide variation in definitions of TBI and coagulopathy (table 1). Coagulopathy occurs in more than 60% of patients with severe TBI,3,4 but is uncommon in mild head injury (<1%).35 Although the prevalence of coagulopathy in isolated TBI (ie, in the absence of additional traumatic injuries) is not higher when compared with systemic injuries of similar severity, the coincidence of both TBI and systemic injury could substantially increase the magnitude of coagulopathy beyond that seen in the isolated condition.19,23,36–38
Normal haemostasis depends on an intricate balance between mechanisms of bleeding and mechanisms of thrombosis, and this balance can be altered after traumatic brain injury (TBI). Impaired haemostasis could exacerbate the primary insult with risk of initiation or aggravation of bleeding; anticoagulant use at the time of injury can also contribute to bleeding risk after TBI. Many patients with TBI have abnormalities on conventional coagulation tests at admission to the emergency department, and the presence of coagulopathy is associated with increased morbidity and mortality. Further blood testing often reveals a range of changes affecting platelet numbers and function, procoagulant or anticoagulant factors, fibrinolysis, and interactions between the coagulation system and the vascular endothelium, brain tissue, inflammatory mechanisms, and blood flow dynamics. However, the degree to which these coagulation abnormalities affect TBI outcomes and whether they are modifiable risk factors are not known. Although the main challenge for management is to address the risk of hypocoagulopathy with prolonged bleeding and progression of haemorrhagic lesions, the risk of hypercoagulopathy with an increased prothrombotic tendency also warrants consideration.
Management of neurologic complications of coagulopathies
2017, Handbook of Clinical Neurology
Citation Excerpt :
There is evidence that injury severity is an important risk factor in predicting coagulopathy. Over 60% of patients with severe TBI have coagulopathy compared to < 1% with mild head injury (Gómez et al., 1996; Hoyt, 2004). Bleeding complications are common in the setting of malignancy, especially leukemias.
Coagulopathy is common in intensive care units (ICUs). Many physiologic derangements lead to dysfunctional hemostasis; these may be either congenital or acquired. The most devastating outcome of coagulopathy in the critically ill is major bleeding, defined by transfusion requirement, hemodynamic instability, or intracranial hemorrhage. ICU coagulopathy often poses complex management dilemmas, as bleeding risk must be tempered with thrombotic potential. Coagulopathy associated with intracranial hemorrhage bears directly on prognosis and outcome. There is a paucity of high-quality evidence for the management of coagulopathies in neurocritical care; however, data derived from studies of patients with intraparenchymal hemorrhage may inform treatment decisions.
Coagulopathy is often broadly defined as any derangement of hemostasis resulting in either excessive bleeding or clotting, although most typically it is defined as impaired clot formation. Abnormalities in coagulation testing without overt clinical bleeding may also be considered evidence of coagulopathy. This chapter will focus on acquired conditions, such as organ failure, pharmacologic therapies, and platelet dysfunction that are associated with defective clot formation and result in, or exacerbate, intracranial hemorrhage, specifically spontaneous intraparenchymal hemorrhage and traumatic brain injury.
Critical care management of traumatic brain injury
2017, Handbook of Clinical Neurology
Citation Excerpt :
At the other end of the translational pathway there has been increasing interest in using precision medicine and comparative effectiveness research (Maas et al., 2012) to advance research and clinical care in TBI – these themes are the focus of a large international initiative (http://intbir.nih.gov/). TBI is associated with both hemostatic deficits and hypercoagulopathy (Laroche et al., 2012; Maegele, 2013), with up to 60% of patients showing abnormal values in severe TBI (Hoyt, 2004). Risk factors include injury severity, age, and prehospital hypotension (Wafaisade et al., 2010a, b).
Traumatic brain injury (TBI) is a growing global problem, which is responsible for a substantial burden of disability and death, and which generates substantial healthcare costs. High-quality intensive care can save lives and improve the quality of outcome. TBI is extremely heterogeneous in terms of clinical presentation, pathophysiology, and outcome. Current approaches to the critical care management of TBI are not underpinned by high-quality evidence, and many of the current therapies in use have not shown benefit in randomized control trials. However, observational studies have informed the development of authoritative international guidelines, and the use of multimodality monitoring may facilitate rational approaches to optimizing acute physiology, allowing clinicians to optimize the balance between benefit and risk from these interventions in individual patients. Such approaches, along with the emerging impact of advanced neuroimaging, genomics, and protein biomarkers, could lead to the development of precision medicine approaches to the intensive care management of TBI.
Carboxyfullerene nanoparticles alleviate acute hepatic injury in severe hemorrhagic shock
2017, Biomaterials
Citation Excerpt :
Hemorrhagic shock is the leading cause of potentially preventable deaths in civilian and military trauma, accounting for up to 40% of the deaths associated with traumatic injuries [1].
Hemorrhagic shock/resuscitation involves overwhelming reactive oxygen species (ROS) that cause oxidative stress, inflammation, and subsequent tissue injury. We investigated the effects of the potent antioxidant carboxyfullerene (C₃) on acute liver injury during hemorrhage shock/resuscitation. C₃ infusion reduced the alanine aminotransferase (ALT) activity, methemoglobin content, malondialdehyde content, myeloperoxidase activity and expression levels of tumor necrosis factor -α and interleukin-6; it increased superoxide dismutase activity in the liver. The histologic injury score and apoptotic index were also markedly decreased after C₃ treatment compared with the vehicle group. Additionally, C₃-treated rats showed a significant decrease in nuclear factor-κB DNA binding capacity, which was preceded by reduced phosphorylation of the nuclear factor κB (NF-κB) p65 subunit in the liver. C₃ nanoparticles ameliorate oxidative stress, the inflammatory response, and subsequent acute liver injury after hemorrhagic shock/resuscitation. These protective effects appear to be mediated through the inhibition of the nuclear factor-κB pathway. C₃ treatment may be a promising strategy to improve tissue injury in hemorrhagic shock/resuscitation.
Low-dose recombinant factor VIIa for reversing coagulopathy in patients with isolated traumatic brain injury
2015, Journal of Critical Care
Citation Excerpt :
Traumatic brain injury (TBI) is a leading cause of injury-related hospitalization, disability, and death worldwide [1]. Coagulopathies are common in patients with TBI [2,3]. In a previous study, we demonstrated that coagulation abnormalities were present in about 50% of patients with severe TBI [4].
The purpose of this study was to investigate the role of low-dose recombinant factor VIIa (rFVIIa) (20 μg/kg) in reversing coagulopathy in patients with isolated traumatic brain injury (TBI).
Patients with isolated TBI and coagulopathy at admission were enrolled prospectively from January 2010 to December 2011. The patients were divided into 2 groups: the rFVIIa and the no-rFVIIa groups. In the rFVIIa group, patients received a single dose of 20 μg/kg rFVIIa intravenously to reverse their coagulopathy in addition to blood products. Patients in the no-rFVIIa group received only blood products to correct the coagulopathy. The clinical outcome variables evaluated included changes in coagulation parameters after administration for reversing coagulopathy, the occurrence of progressive hemorrhagic injury (PHI), intensive care unit length of stay, the incidence of thromboembolic complications, inhospital mortality, and 90-day Glasgow Outcome Scale.
Eighty-seven patients were ultimately included in this study. Of them, 49 patients were treated with blood products alone, whereas 38 patients also received rFVIIa to reverse their coagulopathy. The improvement in international normalized ratio was greater in the rFVIIa group (0.26 [0.18-0.39]) than in the no-rFVIIa group (0.06 [− 0.11 to 0.30]) (P = .001). In addition, the improvement in lactate was also greater in the rFVIIa group (0.33 [− 0.18 to 0.54]) than in the no-rFVIIa group (0.04 [− 0.25 to 0.20]) (P = .029). During the period after we began to correct the coagulopathy, PHI occurred in 19 patients (38.8%) in the no-rFVIIa group, which was significantly higher than that in the rFVIIa group (7, 18.4%; P = .040). The rate of cerebral infarction was similar in both groups (10.2% vs 5.3%). There was a trend indicating that low-dose rFVIIa therapy was associated with a lower mortality, but the association was not statistically significant (P = .266).
The use of low-dose rFVIIa (20 μg/kg) is effective for correcting coagulopathy in patients with TBI without an increase in thromboembolic events. Moreover, it is more effective for preventing the occurrence of PHI.

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PaperA clinical review of bleeding dilemmas in trauma

Abstract

Section snippets

The changing role of fluid resuscitation

Potential roles of procoagulant therapy

Conclusions

J Am Coll Surg

Am J Med

Ann Emerg Med

Immediate versus delayed fluid resuscitation for hypotensive patients with penetrating torso injuries

N Engl J Med

Immunomodulatory effects of allogeneic blood transfusionsClinical manifestations and mechanisms

Vox Sang

An assessment of the potential for reducing future combat deaths through medical technologies and training

J Trauma

Traumatic Shock

A profile of combat injury

J Trauma

Blood transfusions correlate with infections in trauma patients in a dose-dependent manner

Am Surg

Resuscitation in uncontrolled hemorrhage

Am Surg

Limited volume resuscitation in penetrating thoracoabdominal trauma

AACN Clin Issues

Paper
A clinical review of bleeding dilemmas in trauma