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.     

Early coagulopathy predicts mortality in trauma

BACKGROUND: Coagulopathy and hemorrhage are known contributors to trauma mortality; however, the actual relationship of prothrombin time (PT) and partial thromboplastin time (PTT) to mortality is unknown. Our objective was to measure the predictive value of the initial coagulopathy profile for trauma-related mortality. METHODS: We reviewed prospectively collected data on trauma patients presenting to a Level I trauma center. A logistic regression analysis was performed of PT, PTT, platelet count, and confounders to determine whether coagulopathy is a predictor of all-cause mortality. RESULTS: From a trauma registry cohort of 20103 patients, 14397 had complete disposition data for initial analysis and 7638 had complete data for all variables in the final analysis. The total cohort was 76.2% male, the mean age was 38 years (range, 1-108 years), and the median Injury Severity Score was 9. There were 1276 deaths (all-cause mortality, 8.9%). The prevalence of coagulopathy early in the postinjury period was substantial, with 28% of patients having an abnormal PT (2994 of 10790) and 8% of patients having an abnormal PTT (826 of 10453) on arrival at the trauma bay. In patients with disposition data and a normal PT, 489 of 7796 died, as compared with 579 of 2994 with an abnormal PT (6.3% vs. 19.3%; chi2 = 414.1, p < 0.001). Univariate analysis generated an odds ratio of 3.6 (95% confidence interval [CI], 3.15-4.08; p < 0.0001) for death with abnormal PT and 7.81 (95% CI, 6.65-9.17; p < 0.001) for deaths with an abnormal PTT. The PT and PTT remained independent predictors of mortality in a multiple regression model, whereas platelet count did not. The model also included the independent risk factors age, Injury Severity Score, scene and trauma-bay blood pressure, hematocrit, base deficit, and head injury. The model generated an adjusted odds ratio of 1.35 for PT (95% CI, 1.11-1.68; p < 0.001) and 4.26 for PTT (95% CI, 3.23-5.63; p < 0.001). CONCLUSION: The incidence of coagulation abnormalities, early after trauma, is high and they are independent predictors of mortality even in the presence of other risk factors. An initial abnormal PT increases the adjusted odds of dying by 35% and an initial abnormal PTT increases the adjusted odds of dying by 326%.     

The incidence of alcohol abuse and coagulopathy in penetrating abdominal trauma

Preexisting coagulopathy or hepatic dysfunction is a potential problem in the alcoholic with penetrating abdominal trauma. This study reviews 36 patients with penetrating abdominal trauma to determine evidence of acute and/or chronic alcohol abuse, evidence of hepatic dysfunction, preexisting coagulopathy, pattern of blood use, and severity of injury. Sixty-four per cent of patients had detectable blood alcohol concentrations (BAC) on admission and 50% were legally intoxicated. Alcohol consumption histories were available for 24 patients, and 15 (63%) were chronic alcohol abusers. There was little evidence of hepatic dysfunction and minimal coagulopathy. There was a significant difference in the number of chronic alcohol abusers who received blood and in the amount used by any individual. There is nothing in this study to suggest this increased blood use would be lessened by including fresh frozen plasma, Vitamin K, or platelet packs in the initial resuscitation of the alcoholic patient with penetrating abdominal trauma.     

Diagnosis and management of coagulopathy after major trauma

This is the third leading article in the Journal's series on major trauma. In it Karim Brohi, Professor of Trauma Sciences at Queen Mary University of London, deals with the important topic of the defects in blood coagulation that are often encountered after serious injury. Copyright © 2009 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd.     

Massive hemorrhage and mechanisms of coagulopathy in trauma

Trauma is disease of the young, mainly affecting people between 15-40 years of age. Uncontrolled massive bleeding is the leading cause of early in-hospital mortality, within 48h of admission, and the second leading cause of prehospital death in victims of both military and civilian trauma, accounting for 40-45% of the total fatalities. Coagulopathy develops early after injury and is present in 25-36% of trauma victims upon admission to the emergency department. Coagulopathy correlates to the severity of trauma and is associated with an increased risk of mortality. The aim of this paper is to explain pathophysiology of developing coagulopathy in trauma. The coagulopathy in the trauma patient is complex and multifactorial. It includes: dilutional coagulopathy, hypothermia, acidosis, hyperfibrinolysis, anemia and consumption coagulopathy. When the patient develops the so called "lethal triad" of hypothermia, acidosis and coagulopathy, surgical restoration of vascular integrity may be insufficient to achieve a deffinitive control of blood loss and non-mechanical bleeding from small vessels, usually terminated by spontaneous coagulation, becomes a life-threatening condition.     

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.     

Low-dose recombinant factor VIIa for trauma patients with coagulopathy

INTRODUCTION: Coagulopathy in injured patients is common and is generally treated with fresh frozen plasma (FFP). Response can be variable, thus complete correction may take hours and require large volumes of fluids. High-dose recombinant factor VIIa (FVIIa, Novoseven, Novo Nordisk, Bagsvaerd, Denmark) has been used off-label to treat severe coagulopathy following trauma. Expense has limited use. Recently, we began administering low dose FVIIa (1.2mg) to patients with mild to moderate coagulopathy after trauma, hypothesising that it would be effective and safe. PATIENTS AND METHODS: We retrospectively reviewed consecutive patients who received a low dose of 1.2mg of FVIIa over a 2-year period. Factor VIIa is administered after approval by a gatekeeper at the discretion of the treating physician. Demographics, injury and laboratory data were abstracted as were indications for use, source of coagulopathy, effectiveness, and complications. A two-tailed paired t-test was used to determine significant changes in coagulation parameters and blood product utilisation. RESULTS: Eighty-one patients received 84 low doses of FVIIa. The mean age of the patients was 51 (+/-22) with a mean ISS of 29 (+/-11). Seventy-three per cent were male and 67% had a traumatic brain injury (TBI) as their primary injury. The aetiology of the coagulopathy in the study population included; TBI (40%), warfarin use (22%), and cirrhosis (13%). Mean prothrombin time (PT) fell from 17.0s (+/-3.2) to 10.6s (+/-1.4) (p<0.0001). All patients had a good clinical response with no bleeding complications. Utilisation of packed red blood cells and fresh frozen plasma were significantly less in the 24h after FVIIa administration as compared to the 24h prior. Subsequent thromboembolic events were observed in 12 of the 81 patients (15%) and included; cerebrovascular accident (CVA) (6), mesenteric thrombosis (2), myocardial infarction (MI) (1), pulmonary embolism/deep venous thrombosis (PE/DVT) (2), and atrial thrombus (1). Only four of these events were thought to be related to the FVIIa administration, with two of the four contributing to a lethal outcome. CONCLUSIONS: Low dose FVIIa rapidly and effectively treats mild to moderate coagulopathy following injury. This low dose (1.2mg) FVIIa is the smallest available unit dose. It costs approximately the same as 8 units of plasma and may be cost-effective in patients who require high volume factor administration. Low dose FVIIa may be effective in coagulopathic trauma patients who are not in shock but require rapid normalisation of clotting function.     

严重创伤合并创伤性凝血病的临床治疗分析

目的分析重组人凝血因子Ⅶa在严重创伤合并创伤性凝血病患者中的临床治疗效果。方法严重创伤合并创伤性凝血病患者42例,其中治疗组17例,给予重组人凝血因子Ⅶa治疗,对照组25例。所有患者均按损伤控制原则救治,比较两组患者治疗后的凝血功能指标、总输血量[红细胞(RBC)与新鲜冰冻血浆(FFP)]、ICU住院时间及死亡率。结果治疗组患者的RBC和FFP总输注量分别为(17.13±3.68)U和(15.98±5.13)U,对照组患者分别为(21.42±5.60)U和(20.18±4.57)U,两组比较差异有统计学意义(P0.05);治疗组患者ICU住院时间和死亡率分别为(4.3±1.6)天和17.6%,对照组患者分别为(5.6±1.8)天和(48.0%),两组比较差异有统计学意义(P0.05);治疗12小时和24小时后,治疗组凝血酶原时间(PT)、部分凝血活酶时间(APTT)、国际标准化比值(INR)及纤维蛋白原(FIB)指标明显改善,优于对照组(P0.05或P0.01)。结论创伤性凝血病患者给予重组人凝血因子Ⅶa,能改善患者的外源性凝血功能,减少输血总量,缩短ICU住院时间,降低死亡率。     

Delayed brain injury after head trauma: significance of coagulopathy.

We reviewed the records of 253 patients with head injury who required serial computed tomographic (CT) scans; 123 (48.6%) developed delayed brain injury as evidenced by new or progressive lesions after a CT scan. An abnormality in the prothrombin time, partial thromboplastin time, or platelet count at admission was present in 55% of the patients who showed evidence of delayed injury, and only 9% of those whose subsequent CT scans were unchanged or improved from the time of admission (P less than 0.001). Among patients developing delayed injury, mean prothrombin time at admission was significantly longer (14.6 vs. 12.6 s, P less than 0.001) and partial thromboplastin time was significantly longer (36.9 vs. 29.2 s, P less than 0.001) than patients who did not have delayed injury. If coagulation studies at admission were normal, a patient with head injury had a 31% risk of developing delayed insults. This risk rose to almost 85% if at least one clotting test at admission was abnormal (P less than 0.001). We conclude that clotting studies at admission are of value in predicting the occurrence of delayed injury. If coagulopathy is discovered in the patient with head injury early follow-up CT scanning is advocated to discover progressive and new intracranial lesions that are likely to occur.     

Use of recombinant activated factor VII to treat the acquired coagulopathy of trauma

Recombinant activated factor VII (rFVIIa) is a drug commonly utilized in the treatment of patients with hemophilia and inhibitors. However, its use in previously normal patients with an acquired coagulopathy after trauma and surgery is increasing. Multiple trauma case reports and several case series are available, lending support for the efficacy of the drug in reversing the coagulopathy of trauma. Data from six large animal studies evaluating the efficacy in trauma models are available for evaluation. A single prospective randomized study in elective surgery has recently been published, documenting reduced blood loss and decreased transfusion after a single preoperative dose. This review describes those studies and reiterates the need for well designed prospective randomized human trauma studies.     

Early coagulopathy in trauma patients: an on-scene and hospital admission study

PurposeAmongst trauma patients, early coagulopathy is common on hospital admission. No studies have evaluated the initial coagulation status in the pre-hospital setting. We hypothesise that the coagulopathic process begins at the time of trauma. We studied the on-scene and on hospital arrival coagulation profile of trauma patients.MethodsProspective, observational study investigating the on-scene coagulation profile and its time course. We studied 45 patients at the scene of the accident, before fluid administration, and on hospital admission and classified their coagulopathy using the International Society on Thrombosis and Haemostasis score during a 2-month period. Prothrombin time, activated partial thromboplastin time, fibrinogen concentration, factors II, V and VII activity, fibrin degradation products, antithrombin and protein C activities, platelet counts and base deficit were measured.ResultsThe median injury severity score was 25 (13–35). On-scene, coagulation status was abnormal in 56% of patients. Protein C activities were decreased in the trauma-associated coagulopathy group (p = .02). Drops in protein C activities were associated with changes in activated partial thromboplastin time, prothrombin time, fibrinogen concentration, factor V and antithrombin activities. Only factor V levels decreased significantly with the severity of the trauma. On hospital admission, coagulation status was abnormal in 60% of patients. The on-scene coagulopathy was spontaneously normalised only in 2 patients whereas others had the same or a poorer coagulopathy status. All parameters of coagulation were significantly abnormal comparing to the on-scene phase. Decreases in protein C activities were related to the coagulation status (p < .0001) and changes in other coagulation parameters. Patients with base deficit ≤?6 mmol/L had changes in antithrombin, factor V and protein C activities but no significant coagulopathy.ConclusionCoagulopathy occurs very early after injury, before fluid administration, at the site of accident. Coagulation and fibrinolytic systems are activated early. The incidence of coagulopathy is high and its severity is related to the injury and not to hypoperfusion.