Are we giving enough coagulation factors during major trauma resuscitation?

Hemorrhage is a major cause of trauma deaths. Coagulopathy exacerbates hemorrhage and is commonly seen during major trauma resuscitation, suggesting that current practice of coagulation factor transfusion is inadequate. Reversal of coagulopathy involves normalization of body temperature, elimination of the causes of disseminated intravascular coagulation (DIC), and transfusion with fresh-frozen plasma (FFP), platelets, and cryoprecipitate. Transfusion should be guided by clinical factors and laboratory results. However, in major trauma, clinical signs may be obscured and various factors conspire to make it difficult to provide the best transfusion therapy. Existing empiric transfusion strategies for, and prevailing teachings on, FFP transfusion appear to be based on old studies involving elective patients transfused with whole blood and may not be applicable to trauma patients in the era of transfusion with packed red blood cells (PRBCs). Perpetuation of such concepts is in part responsible for the common finding of refractory coagulopathy in major trauma patients today. In this review, we argue that coagulopathy can best be avoided or reversed when severe trauma victims are transfused with at least the equivalent of whole blood in a timely fashion.     

The acute coagulopathy of trauma shock: Clinical relevance

Recent observational studies have identified an acute coagulopathy in trauma victims that is present on arrival in the emergency room. It has been associated with a four-fold increase in mortality and increased incidence of organ failure. Conventional trauma resuscitation and transfusion protocols are designed for dilutional coagulopathy and appear inadequate in the management of acute traumatic coagulopathy and massive transfusion.Acute Coagulopathy of Trauma Shock (ACoTS) is caused by a combination of tissue injury and shock, and may occur without significant fluid administration, clotting factor depletion or hypothermia. The mechanism through which acute coagulopathy develops is unclear but activation of the protein C pathway has been implicated.Standard coagulation tests do not identify cases in a timely fashion and ACoTS should be suspected in any trauma patient with a significant magnitude of injury and shock, as evidenced by an abnormal admission base deficit on blood gas. Development of point of care coagulometers and whole blood coagulation analysers, such as rotational thromboelastometry, may enable earlier laboratory identification of this group. Retrospective studies performed by the American military indicate that resuscitation of severely injured patients with higher ratios of plasma given early may improve outcome and reduce overall blood product use. The place of adjunctive pharmaceutical agents within this strategy remains unclear.There is an acute coagulopathy associated with trauma and shock that is an independent predictor of outcomes. Delineation of this entity, with directed management protocols should lead to a reduction in avoidable deaths from haemorrhage after trauma.     

What's new in resuscitation strategies for the patient with multiple trauma?

The last decade has seen a sea change in the management of major haemorrhage following traumatic injury. Damage control resuscitation (DCR), a strategy combining the techniques of permissive hypotension, haemostatic resuscitation and damage control surgery has been widely adopted as the preferred method of resuscitation in patients with haemorrhagic shock. The over-riding goals of DCR are to mitigate metabolic acidosis, hypothermia and coagulopathy and stabilise the patient as early as possible in a critical care setting. This narrative review examines the background to these changes in resuscitation practice, discusses the central importance of traumatic coagulopathy in driving these changes particularly in relation to the use of high FFP:RBC ratio and explores methods of predicting, diagnosing and treating the coagulopathy with massive transfusion protocols as well as newer coagulation factor concentrates. We discuss other areas of trauma haemorrhage management including the role of hypertonic saline and interventional radiology. Throughout this review we specifically examine whether the available evidence supports these newer practices.     

Blood transfusion in trauma patients: unresolved questions

Massive transfusion is an essential part of resuscitation efforts in acute trauma patients. The goal is to quickly correct trauma-induced coagulopathy and replace red blood cell (RBC) mass with the minimal number as well as the appropriate choice of blood components to minimize the possible adverse effects of transfusions. Early trauma induced coagulopathy (ETIC) is present in about 20% of patients upon hospital admission and predicts for decreased survival. The mechanism of ETIC is still being elucidated; however, most theories of ETIC's pathophysiology justify the early use of plasma. Most massive transfusion protocol (MTP) ratios deliver blood products in a ratio of 1:1:1 for RBCs:plasma:platelets, which is supported by the majority of the literature demonstrating improved patient survival with higher ratios (>1 plasma and platelet for every 2 RBCs transfused). Indeed, formula-driven MTPs allow trauma services to react quickly to ETIC and provide coagulation factors and platelets in these ratios without having to wait for the results of coagulation assays while the patient's coagulopathy worsens. New MTPs are being created which are adjusted according to an individual's coagulation laboratory values based on point-of-care laboratory tests, such as thromboelastography. When creating an MTP, product wastage due to inappropriate activation and improper product storage should be considered and closely monitored. Another area of discussion regarding transfusion in trauma includes the potential association of prolonged storage of RBCs and adverse outcomes, which has yet to be confirmed. Significant progress has been made in the transfusion management of trauma patients, but further studies are required to optimize patient care and outcomes.     

Trauma-induced coagulopathy

Hemorrhage is the leading cause of death in trauma patients who arrive alive at hospital. This type of hemorrhage has a “coagulopathic” component, specific to major trauma and associated with poor outcomes. Over the last decade, a better understanding of this trauma-induced coagulopathy lead to a new therapeutic approach requiring earlier and more aggressive management. This hemostatic resuscitation includes early activation of massive transfusion protocols with: 1) immediate delivery of blood packs with high ratios for RBC units: fresh frozen plasma: platelet-concentrates; 2) antifibrinolytics; 3) substitution of coagulation factors. However, early identification of coagulopathic patients requiring aggressive hemostatic resuscitation remains challenging, with an increasing role of point of care devices for hemostatic diagnosis and monitoring. Efforts have to be focused on the early diagnosis of coagulopathy for immediate delivery of blood products and coagulation factors to the right, accurately screened patients through pre-established protocols within the golden hour.     

Management of major blood loss: An update

Haemorrhage remains a major cause of potentially preventable deaths. Trauma and massive transfusion are associated with coagulopathy secondary to tissue injury, hypoperfusion, dilution and consumption of clotting factors and platelets. Concepts of damage control surgery have evolved, prioritizing the early control of the cause of bleeding by non‐definitive means, while haemostatic control resuscitation seeks early control of coagulopathy. Haemostatic resuscitation provides transfusions with plasma and platelets in addition to red blood cells (RBCs) in an immediate and sustained manner as part of the transfusion protocol for massively bleeding patients. Transfusion of RBCs, plasma and platelets in a similar proportion as in whole blood prevents both hypovolaemia and coagulopathy. Although an early and effective reversal of coagulopathy is documented, the most effective means of preventing coagulopathy of massive transfusion remains debated and randomized controlled studies are lacking. Results from recent before‐and‐after studies in massively bleeding patients indicate that trauma exsanguination protocols involving the early administration of plasma and platelets are associated with improved survival. Furthermore, viscoelastic whole blood assays, such as thrombelastography (TEG)/rotation thromboelastometry (ROTEM), appear advantageous for identifying coagulopathy in patients with severe haemorrhage, as opposed to conventional coagulation assays. In our view, patients with uncontrolled bleeding, regardless of its cause, should be treated with goal‐directed haemostatic control resuscitation involving the early administration of plasma and platelets and based on the results of the TEG/ROTEM analysis. The aim of the goal‐directed therapy should be to maintain a normal haemostatic competence until surgical haemostasis is achieved, as this appears to be associated with reduced mortality.     

Research progress of acute coagulopathy of trauma-shock

Acute coagulopathy of trauma-shock (ACoTS) occurs in 25% of patients with severe trauma in the early phase, and the mortality of those patients is four-fold higher than patients without coagulopathy. The pathophysiology of this complicated phenomenon has been focused on in recent years. Tissue injury and hypoperfusion, activated protein C and Complements play important roles in the early phase after trauma. While the use of blood products, hypothermia, acidosis and inflammation are the main mechanism in late phase. Supplementing coagulation factors and platelets to improve ACoTS are inefficient. Only positive resuscitation from shock and improving tissue hypoperfusion have expected benefits.     

Le concept de damage control resuscitation

Objective

Damage control is a strategy of care for bleeding trauma patients, involving minimal rescue surgery associated to perioperative resuscitation. The purpose of this review is to draw up a statement on current knowledge available on damage control.

Data sources

References were obtained from recent review articles, personal files, and Medline database research of English and French publications. All categories of articles on this topic have been selected.

Data synthesis

Historical damage control surgery, that consist of abbreviated laparotomy with second-look after resuscitation, is now included in a wider concept called “damage control resuscitation”, addressing the lethal triad (coagulopathy, hypothermia and acidosis) at an early phase. Care is focused on coagulopathy prevention. Early resuscitation, or damage control ground zero, has been improved: aggressive management of hypothermia, bleeding control techniques, permissive hypotension concept and early use of vasopressors. Transfusion practices also have evolved: early platelets and coagulation factors administration, use of hemostatic agents like recombinant FVIIa, whole blood transfusion, denote the damage control hematology. Progress in surgical practices and development of arteriographic techniques lead to wider indications of damage control strategy.     

Koagulopathie

Coagulopathy after trauma is a major cause for uncontrolled hemorrhage in trauma vicitims. Approximately 40% of trauma related deaths are attributed to or caused by exsanguination. Therefore the prevention of coagulopathy is regarded as the leading cause of avoidable death in these patients. Massive hemorrhage after trauma is usually caused by a combination of surgical and coagulopathic bleeding. Coagulopathic bleeding is multifactorial, including dilution and consumption of both platelets and coagulation factors, as well as dysfunction of the coagulation system. Because of the high mortality associated with hypothermia, acidosis and progressive coagulopathy, this vicious circle is often referred to as the lethal triad, potentially leading to exsanguination. To overcome this coagulopahty-related bleeding an empiric therapy is often instituted by replacing blood components. However, the use of transfusion of red blood cells has been shown to be associated with post-injury infection and multiple organ failure. In the management of mass bleeding it is therefore crucial to have a clear strategy to prevent coagulopathy and to minimize the need for blood transfusion.     

Coagulopathy in multiple trauma: new aspects of therapy

Coagulopathy after trauma is a major cause for uncontrolled hemorrhage in trauma victims. Approximately 40% of trauma related deaths are attributed to or caused by exsanguination. Therefore the prevention of coagulopathy is regarded as the leading cause of avoidable death in these patients. Massive hemorrhage after trauma is usually caused by a combination of surgical and coagulopathic bleeding. Coagulopathic bleeding is multifactorial, including dilution and consumption of both platelets and coagulation factors, as well as dysfunction of the coagulation system. Because of the high mortality associated with hypothermia, acidosis and progressive coagulopathy, this vicious circle is often referred to as the lethal triad, potentially leading to exsanguination. To overcome this coagulopahty-related bleeding an empiric therapy is often instituted by replacing blood components. However, the use of transfusion of red blood cells has been shown to be associated with post-injury infection and multiple organ failure. In the management of mass bleeding it is therefore crucial to have a clear strategy to prevent coagulopathy and to minimize the need for blood transfusion.     

Blood component therapy in trauma guided with the utilization of the perfusionist and thromboelastography

25-35% of all seriously injured multiple trauma patients are coagulopathic upon arrival to the emergency department, and therefore early diagnosis and intervention on this subset of patients is important. In addition to standard plasma based tests of coagulation, the thromboelastogram (TEG) has resurfaced as an ideal test in the trauma population to help guide the clinician in the administration of blood components in a goal directed fashion. We describe how thromboelastographic analysis is used to assist in the management of trauma patients with coagulopathies presenting to the emergency department, in surgery, and in the postoperative period. Indications for the utilization of the TEG and platelet mapping as point of care testing that can guide blood component therapy in a goal directed fashion in the trauma population are presented with emphasis on the more common reasons such as massive transfusion protocol, the management of traumatic brain injury with bleeding, the diagnosis and management of trauma in patients on platelet antagonists, the utilization of recombinant FVIIa, and the management of coagulopathy in terminal trauma patients in preparation for organ donation. The TEG allows for judicious and protocol assisted utilization of blood components in a setting that has recently gained acceptance. In our program, the inclusion of the perfusionist with expertise in performing and interpreting TEG analysis allows the multidisciplinary trauma team to more effectively manage blood products and resuscitation in this population.     

Thromboelastometry during intraoperative transfusion of fresh frozen plasma in pediatric neurosurgery

Normal blood coagulation is essential in pediatric neurosurgery because of the risk of abundant bleeding, and therefore it is important to avoid transfusion of fluids that might interfere negatively with the coagulation process. There is a lack of transfusion guidelines in massive bleeding with pediatric neurosurgical patients, and early use of blood compounds is partly controversial. We describe two pediatric patients for whom fresh frozen plasma (FFP) infusion was started at the early phase of brain tumor surgery to prevent intraoperative coagulopathy and hypovolemia. In addition to the traditional laboratory testing, modified thromboelastometry analyses were used to detect possible disturbances in coagulation. Early transfusion of FFP and red blood cells preserved the whole blood coagulation capacity. Even with continuous FFP infusion, fibrin clot firmness was near to critical value at the end of surgery despite increased preoperative values. By using FFP instead of large amounts of crystalloids and colloids when major blood loss is expected, blood coagulation is probably less likely to be impaired. Our results indicate, however, that the capacity of FFP to correct fibrinogen deficit is limited.     

Rahmenbedingungen für eine intakte Hämostase

A coagulopathy is an independent predictor of perioperative mortality. Therefore, maintenance of a functional coagulation system is an essential precondition to reduce morbidity and mortality in the perioperative setting. Sound coagulability also depends on prerequisites such as body temperature, acid-base balance, plasma calcium concentration and haematocrit. Severe trauma or perioperative bleeding can gravely influence these factors and boost the blood loss. Common global tests of coagulation are not helpful in this setting because they are conducted on plasma with a normalised temperature of 37 degrees C, an excess of calcium and a stabile acid-base balance. Hence, knowledge of the effects of altered prerequisites is a premise to avoid a possibly lethal coagulopathy. According to the current literature, an increased risk for clinically significant coagulopathy exists with a body temperature 相似文献   

Acute coagulopathy and early deaths post major trauma

Introduction and aimsAcute traumatic coagulopathy is observed in 10–25% of patients post major trauma and its management forms an integral part of haemostatic resuscitation. The identification and treatment of this coagulopathy is difficult and there is uncertainty regarding optimal therapeutic guidelines during the early phases of trauma resuscitation. This study aimed to examine the association between acute coagulopathy and early deaths post major trauma.MethodsA retrospective review of data over a 5 year period was performed to determine the associations between variables considered to contribute to mortality for adult major trauma patients (Injury Severity Score (ISS) > 15) receiving blood transfusions as part of their initial resuscitation. Early death, defined as death in ED, or death in the operating theatre (OT), Intensive Care Unit (ICU) or wards within 24 h of admission was the primary end-point. Patients with non-survivable head injury on initial imaging were excluded. Univariate associations were calculated and multivariable logistic regression analysis was used to determine independent associations with mortality.ResultsThere were 772 patients included in this study with a median ISS of 29 (19–41), with 91.7% blunt trauma. All-cause in-hospital mortality was 17.5%, while 77 (9.7%) patients died early. Increasing age (OR 1.04), a GCS of 3–8 (OR 5.05), and the presence of acute coagulopathy (OR 8.77) were significant independent variables associated with early death.ConclusionsAcute traumatic coagulopathy, independent of injury severity, transfusion practice or other physiological markers for haemorrhage, was associated with early death in major trauma patients requiring a blood transfusion. Early recognition and management of coagulopathy, independent of massive transfusion guidelines, may improve outcome from trauma resuscitation. Further studies are required for the early recognition of acute traumatic coagulopathy to enable the development of an evidence base for management.     

Pädiatrisches stumpfes thorakoabdominales Trauma

Primary resuscitation and therapeutic management of children with severe blunt abdominal trauma with accompanying acidosis, coagulopathy and hypothermia (lethal triad) necessitate an efficient multidisciplinary regimen to minimize mortality. A boy aged 5.5 years presented with severe abdominal trauma, including splenic rupture grade IV, hepatic rupture grade III, pancreatic laceration grade III, bilateral pulmonary contusions and abdominal wall contusion with rhabdomyolysis. He had been crushed between the rear wheel of a tractor and the frame of a gate at a mountain farm. Because severe trauma with coagulopathy and metabolic-respiratory acidosis were present, primary blood products were given instead of crystalloids. Permissive hypotension was tolerated, the body temperature was corrected in accordance with damage control resuscitation guidelines and spleen-preserving surgery was performed. This case report discusses a possible therapeutic strategy including massive transfusion in severe abdominal trauma in a child.     

创伤患者的输血管理

随着对创伤性凝血功能障碍的机制和晶体输液局限性的进一步了解,以及大量输血方案（massivetransfusionproto。col,MTP）的建立,对需要大量输血的创伤患者的管理有了一定的改善。MTP包括输血管理及为减轻致死性三联征（低温、酸中毒、凝血功能障碍）的措施。近来的数据显示早期积极地利用近似于全血的血制品来进行输血急救能够明显降低死亡率,因此目前在美国和世界范围内MTP有了新的改变。本文中MTP是急救措施中的关键因素,它被定义为对已有致死性三联征的严重创伤患者的一种系统性的治疗方法。MTP需要用足量的血浆及凝血因子来改善患者的预后。目前,在MTP中对于输入的血浆、血小板、冷沉淀以及其他凝血因子的剂量与输入红细胞的剂量间的精确比例并不清楚。目前,在尚未得到前瞻性的随机临床试验的结果时,较倾向于血浆：红细胞：血小板的比例为1：1：1。未来仍需进一步的前瞻性临床试验完善MTP,以提高创伤患者的整体治疗水平。     

Change of transfusion and treatment paradigm in major trauma patients

Trauma promotes trauma‐induced coagulopathy, which requires urgent treatment with fixed‐ratio transfusions of red blood cells, fresh frozen plasma and platelet concentrates, or goal‐directed administration of coagulation factors based on viscoelastic testing. This retrospective observational study compared two time periods before (2005–2007) and after (2012–2014) the implementation of changes in trauma management protocols which included: use of goal‐directed coagulation management; admission of patients to designated trauma centres; whole‐body computed tomography scanning on admission; damage control surgery; permissive hypotension; restrictive fluid resuscitation; and administration of tranexamic acid. The incidence of massive transfusion (≥ 10 units of red blood cells from emergency department arrival until intensive care unit admission) was compared with the predicted incidence according to the trauma associated severe haemorrhage score. All adult (≥ 16 years) trauma patients primarily admitted to the University Hospital Zürich with an injury severity score ≥ 16 were included. In 2005–2007, the observed and trauma associated severe haemorrhage score that predicted the incidence of massive transfusion were identical, whereas in 2012–2014 the observed incidence was less than half that predicted (3.7% vs. 7.5%). Compared to 2005–2007, the proportion of patients transfused with red blood cells and fresh frozen plasma was significantly lower in 2012–2014 in both the emergency department (43% vs. 17%; 31% vs. 6%, respectively), and after 24 h (53% vs. 27%; 37% vs. 16%, respectively). The use of tranexamic acid and coagulation factor XIII also increased significantly in the 2012–2014 time period. Implementation of a revised trauma management strategy, which included goal‐directed coagulation management, was associated with a reduced incidence of massive transfusion and a reduction in the transfusion of red blood cells and fresh frozen plasma.     

A mathematical model for fresh frozen plasma transfusion strategies during major trauma resuscitation with ongoing hemorrhage.

BACKGROUND: Randomized controlled trials of how best to administer fresh frozen plasma (FFP) in the presence of ongoing severe traumatic hemorrhage are difficult to execute and have not been published. Meanwhile, coagulopathy remains a common occurrence during major trauma resuscitation and hemorrhage remains a major cause of traumatic deaths, suggesting that current coagulation factor replacement practices may be inadequate. METHODS: We used a pharmacokinetic model to simulate the dilutional component of coagulopathy during hemorrhage and compared different FFP transfusion strategies for the prevention or correction, or both, of dilutional coagulopathy. Assuming the rates of volume replacement and loss are roughly equal, we derived the hematocrit and plasma coagulation factor concentration over time based on the rate of blood loss and replacement, the hematocrit and coagulation factor concentration of the transfusate, and the hematocrit and plasma factor concentration at the time when FFP transfusion begins. RESULTS: Once excessive deficiency of factors has developed and bleeding is unabated, 1-1.5 units of FFP must be given for every unit of packed red blood cells (PRBC) transfused. If FFP transfusion should start before plasma factor concentration drops below 50% of normal, an FFP:PRBC transfusion ratio of 1:1 would prevent further dilution. CONCLUSION: During resuscitation of a patient who has undergone major trauma, the equivalent of whole-blood transfusion is required to correct or prevent dilutional coagulopathy.     

急性创伤性凝血病与创伤复苏治疗

由创伤引起的急性剖伤性凝血病可发生于创伤早期,通常仅见于休克患者。凝血病产生不可控制的失血是严重创伤的主要死亡原因。关键在患者入院当初,早期发现创伤性凝血病。创伤性凝血病的启动因素可能是组织低灌注引发蛋岛C——凝血酶调节蛋白系统过度活化,产生全身性抗凝和原发性纤溶亢进,从而加大失血量,加重出血性休克。最后导致器官功能衰竭和高病死率。因此,急性创伤性凝血病治疗的焦点在于缩短休克期和低灌注状态。要纠正严重创伤伴发的“致命性三联征”。特别对于微血管出血尚未被制止的严重创伤患者,宜积极输入新鲜血浆、浓缩血小板及冷沉淀物。防止不恰当地应用大量输晶体液,或库存血,或蕊缩红细胞液。在大量失血情况下,输注新鲜全血比成分输血更有优越性。重组活化FVII是促进凝血酶生成的强效药物,需要避一步明确其适应证及局限性。     

Massive transfusion and coagulopathy: pathophysiology and implications for clinical management

PURPOSE: To review the pathophysiology of coagulopathy in massively transfused, adult and previously hemostatically competent patients in both elective surgical and trauma settings, and to recommend the most appropriate treatment strategies. METHODS: Medline was searched for articles on "massive transfusion," "transfusion," "trauma," "surgery," "coagulopathy" and "hemostatic defects." A group of experts reviewed the findings. Principal findings: Coagulopathy will result from hemodilution, hypothermia, the use of fractionated blood products and disseminated intravascular coagulation. The clinical significance of the effects of hydroxyethyl starch solutions on hemostasis remains unclear. Maintaining a normal body temperature is a first-line, effective strategy to improve hemostasis during massive transfusion. Red cells play an important role in coagulation and hematocrits higher than 30% may be required to sustain hemostasis. In elective surgery patients, a decrease in fibrinogen concentration is observed initially while thrombocytopenia is a late occurrence. In trauma patients, tissue trauma, shock, tissue anoxia and hypothermia contribute to the development of disseminated intravascular coagulation and microvascular bleeding. The use of platelets and/or fresh frozen plasma should depend on clinical judgment as well as the results of coagulation testing and should be used mainly to treat a clinical coagulopathy. CONCLUSIONS: Coagulopathy associated with massive transfusion remains an important clinical problem. It is an intricate, multifactorial and multicellular event. Treatment strategies include the maintenance of adequate tissue perfusion, the correction of hypothermia and anemia, and the use of hemostatic blood products to correct microvascular bleeding.