IntroductionThe appropriate strategy for trauma-induced coagulopathy management is under debate. We report the treatment of major trauma using mainly coagulation factor concentrates.MethodsThis retrospective analysis included trauma patients who received ≥ 5 units of red blood cell concentrate within 24 hours. Coagulation management was guided by thromboelastometry (ROTEM®). Fibrinogen concentrate was given as first-line haemostatic therapy when maximum clot firmness (MCF) measured by FibTEM (fibrin-based test) was <10 mm. Prothrombin complex concentrate (PCC) was given in case of recent coumarin intake or clotting time measured by extrinsic activation test (EXTEM) >1.5 times normal. Lack of improvement in EXTEM MCF after fibrinogen concentrate administration was an indication for platelet concentrate. The observed mortality was compared with the mortality predicted by the trauma injury severity score (TRISS) and by the revised injury severity classification (RISC) score.ResultsOf 131 patients included, 128 received fibrinogen concentrate as first-line therapy, 98 additionally received PCC, while 3 patients with recent coumarin intake received only PCC. Twelve patients received FFP and 29 received platelet concentrate. The observed mortality was 24.4%, lower than the TRISS mortality of 33.7% (P = 0.032) and the RISC mortality of 28.7% (P > 0.05). After excluding 17 patients with traumatic brain injury, the difference in mortality was 14% observed versus 27.8% predicted by TRISS (P = 0.0018) and 24.3% predicted by RISC (P = 0.014).ConclusionsROTEM®-guided haemostatic therapy, with fibrinogen concentrate as first-line haemostatic therapy and additional PCC, was goal-directed and fast. A favourable survival rate was observed. Prospective, randomized trials to investigate this therapeutic alternative further appear warranted.

IntroductionThromboelastometry (TEM)-guided haemostatic therapy with fibrinogen concentrate and prothrombin complex concentrate (PCC) in trauma patients may reduce the need for transfusion of red blood cells (RBC) or platelet concentrate, compared with fresh frozen plasma (FFP)-based haemostatic therapy.MethodsThis retrospective analysis compared patients from the Salzburg Trauma Centre (Salzburg, Austria) treated with fibrinogen concentrate and/or PCC, but no FFP (fibrinogen-PCC group, n = 80), and patients from the TraumaRegister DGU receiving ≥ 2 units of FFP, but no fibrinogen concentrate/PCC (FFP group, n = 601). Inclusion criteria were: age 18-70 years, base deficit at admission ≥2 mmol/L, injury severity score (ISS) ≥16, abbreviated injury scale for thorax and/or abdomen and/or extremity ≥3, and for head/neck < 5.ResultsFor haemostatic therapy in the emergency room and during surgery, the FFP group (ISS 35.5 ± 10.5) received a median of 6 units of FFP (range: 2, 51), while the fibrinogen-PCC group (ISS 35.2 ± 12.5) received medians of 6 g of fibrinogen concentrate (range: 0, 15) and 1200 U of PCC (range: 0, 6600). RBC transfusion was avoided in 29% of patients in the fibrinogen-PCC group compared with only 3% in the FFP group (P< 0.001). Transfusion of platelet concentrate was avoided in 91% of patients in the fibrinogen-PCC group, compared with 56% in the FFP group (P< 0.001). Mortality was comparable between groups: 7.5% in the fibrinogen-PCC group and 10.0% in the FFP group (P = 0.69).ConclusionsTEM-guided haemostatic therapy with fibrinogen concentrate and PCC reduced the exposure of trauma patients to allogeneic blood products.

IntroductionPrediction of massive transfusion (MT) among trauma patients is difficult in the early phase of trauma management. Whole-blood thromboelastometry (ROTEM®) tests provide immediate information about the coagulation status of acute bleeding trauma patients. We investigated their value for early prediction of MT.MethodsThis retrospective study included patients admitted to the AUVA Trauma Centre, Salzburg, Austria, with an injury severity score ≥16, from whom blood samples were taken immediately upon admission to the emergency room (ER). ROTEM® analyses (extrinsically-activated test with tissue factor (EXTEM), intrinsically-activated test using ellagic acid (INTEM) and fibrin-based extrinsically activated test with tissue factor and the platelet inhibitor cytochalasin D (FIBTEM) tests) were performed. We divided patients into two groups: massive transfusion (MT, those who received ≥10 units red blood cell concentrate within 24 hours of admission) and non-MT (those who received 0 to 9 units).ResultsOf 323 patients included in this study (78.9% male; median age 44 years), 78 were included in the MT group and 245 in the non-MT group. The median injury severity score upon admission to the ER was significantly higher in the MT group than in the non-MT group (42 vs 27, P < 0.0001). EXTEM and INTEM clotting time and clot formation time were significantly prolonged and maximum clot firmness (MCF) was significantly lower in the MT group versus the non-MT group (P < 0.0001 for all comparisons). Of patients admitted with FIBTEM MCF 0 to 3 mm, 85% received MT. The best predictive values for MT were provided by hemoglobin and Quick value (area under receiver operating curve: 0.87 for both parameters). Similarly high predictive values were observed for FIBTEM MCF (0.84) and FIBTEM A10 (clot amplitude at 10 minutes; 0.83).ConclusionsFIBTEM A10 and FIBTEM MCF provided similar predictive values for massive transfusion in trauma patients to the most predictive laboratory parameters. Prospective studies are needed to confirm these findings.

Severe trauma-related bleeding is associated with high mortality. Standard coagulation tests provide limited information on the underlying coagulation disorder. Whole-blood viscoelastic tests such as rotational thromboelastometry or thrombelastography offer a more comprehensive insight into the coagulation process in trauma. The results are available within minutes and they provide information about the initiation of coagulation, the speed of clot formation, and the quality and stability of the clot. Viscoelastic tests have the potential to guide coagulation therapy according to the actual needs of each patient, reducing the risks of over- or under-transfusion. The concept of early, individualized and goal-directed therapy is explored in this review and the AUVA Trauma Hospital algorithm for managing trauma-induced coagulopathy is presented.

E xsanguination is responsible for 30% to 40% of trauma-related deaths. 1,2 Most of these fatalities occur in the prehospital setting. According to standard coagulation tests (SCTs), one quarter to one third of trauma patients present with coagulopathy on admission to the emergency department. 3Y5 The presence of coagulopathy increases the risk for poor outcomes, thus resulting in threefold to fourfold higher mortality rates. 3,5 Coagulopathic patients are at risk of exsanguination. It is assumed that up to 20% of these fatalities are potentially preventable by early hemostatic intervention. 6 Therefore, timely and reliable identification of the underlying cause of bleeding is paramount to improve survival.Despite remarkable advances in knowledge, the etiology of trauma-induced coagulopathy (TIC) is still not fully understood. Recent concepts suggest an ''endogenous'' TIC primarily driven by shock-associated hypoperfusion in combination with tissue trauma, which activates the protein C pathway, resulting in anticoagulation, hypofibrinogenemia, hyperfibrinolysis (HF), and platelet dysfunction. 7,8 In addition, ''exogenous'' factors such as consumption of coagulation proteins, in particular fibrinogen, and dilution of the remaining coagulation factors, accompanied by other potentiating effects, such as acidosis, hypothermia, and electrolyte disturbance, further contribute to TIC. 9 Importantly, TIC is not uniform but varies with pattern of injury and in type during the course of treatment, underscoring the potential importance of point-of-care (POC) testing that can rapidly provide information on an actual individual patient's coagulation status. 10 Conventional plasma-based coagulation testing, such as prothrombin time (PT) or international normalized ratio (INR), and activated partial thromboplastin time (aPTT) fail to fully assess the clotting process. SCTs were designed to evaluate anticoagulation therapy rather than coagulopathy in major trauma. 11 In fact, none of the conventional coagulation tests was developed to predict bleeding or to guide coagulation in the surgical setting. 11Y14 Moreover, a substantial amount of precious time transpires before the results of standard coagulation assessments become available, with a median turnaround time for these tests to be completed at a central laboratory ranging from 78 minutes to 88 minutes. 15,16 Viscoelastic tests (VETs), most commonly thrombelastography (TEG, Haemoscope-Haemonetics, Niles, IL) and rotational thromboelastometry (TEM, Tem Systems Inc., Durham, NC), provide a valuable alternative or an adjunct to SCT in the setting of bleeding in the emergency department. VETs yield rapid, POC assessment of whole-blood coagulation in a variety of conditions in which conventional testing may not be sensitive. 12,15,17,18 Unlike SCT, VETs provide a rapid and dynamic bedside assessment of the initiation and kinetics of clot formation, maximum clot firmness (MCF), and clot breakdown. 12,17,18 VETs can characterize the range of acute coagulopathies present in patient...

Severe traumatic brain injury (sTBI) is often accompanied by coagulopathy and an increased risk of bleeding. To identify and successfully treat bleeding disorders associated with sTBI, rapid assessment of coagulation status is crucial. This retrospective study was designed to assess the potential role of whole-blood thromboelastometry (ROTEM(®), Tem International, Munich, Germany) in patients with isolated sTBI (abbreviated injury scale [AIS](head) ≥3 and AIS(extracranial) <3). Blood samples were obtained immediately following admission to the emergency room of the Trauma Centre Salzburg in Austria. ROTEM analysis (EXTEM, INTEM, and FIBTEM tests) and standard laboratory coagulation tests (prothrombin time index [PTI, percentage of normal prothrombin time], activated partial thromboplastin time [aPTT], fibrinogen concentration, and platelet count) were compared between survivors and non-survivors. Out of 88 patients with sTBI enrolled in the study, 66 survived and 22 died. PTI, fibrinogen, and platelet count were significantly higher in survivors (p<0.005). Accordingly, aPTT was shorter in this group (p<0.0001). ROTEM analysis revealed shorter clotting times in extrinsically activated thromboelastometric test (EXTEM) and intrinsically activated thromboelastometric test (INTEM) (p<0.001), shorter clot formation times in EXTEM and INTEM (p<0.0001), and higher maximum clot firmness in EXTEM, INTEM, and FIBTEM (p<0.01) in survivors compared with non-survivors. Logistic regression analysis revealed extrinsically activated thromboelastometric test with cytochalasin D (FIBTEM) MCF and aPTT to have the best predictive value for mortality. According to the degree of coagulopathy, non-survivors received more RBC (p=0.016), fibrinogen concentrate (p=0.01), and prothrombin complex concentrate (p<0.001) within 24 h of arrival in the emergency room. ROTEM testing appeared to offer an early signal of severe life-threatening sTBI. Further studies are warranted to confirm these results and to investigate the role of ROTEM in guiding coagulation therapy.

Platelets play a central role in coagulation. Currently, information on platelet function following trauma is limited. We performed a retrospective analysis of patients admitted to the emergency room (ER) at the AUVA Trauma Centre, Salzburg, after sustaining traumatic injury. Immediately after admission to the ER, blood was drawn for blood cell counts, standard coagulation tests, and platelet function testing. Platelet function was assessed by multiplate electrode aggregometry (MEA) using adenosine diphosphate (ADPtest), collagen (COLtest) and thrombin receptor activating peptide-6 (TRAPtest) as activators. The thromboelastometric platelet component, measuring the contribution of platelets to the elasticity of the whole-blood clot, was assessed using the ROTEM device. The study included 163 patients, 79.7% were male, and the median age was 43 years. The median injury severity score was 18. Twenty patients (12.3%) died. Median platelet count was significantly lower among non-survivors than survivors (181,000/μl vs. 212,000/μl; p=0.01). Although platelet function defects were relatively minor, significant differences between survivors and non-survivors were observed in the ADPtest (94 vs. 79 U; p=0.0019), TRAPtest (136 vs. 115 U; p<0.0001), and platelet component (134 vs.103 MCEEXTEM - MCEFIBTEM; p=0.0012). Aggregometry values below the normal range for ADPtest and TRAPtest were significantly more frequent in non-survivors than in survivors (p=0.0017 and p=0.0002, respectively). Minor decreases in platelet function upon admission to the ER were a sign of coagulopathy accompanying increased mortality in patients with trauma. Further studies are warranted to confirm these results and investigate the role of platelet function in trauma haemostatic management.

SummaryGoal-directed coagulation therapy is essential in the management of trauma patients with severe bleeding. Due to the complex nature of coagulation disorders in trauma, a quick and reliable diagnostic tool is essential. We report a severely injured multiple trauma patient who received haemostatic therapy with coagulation factor concentrates, guided by rotational thromboelastometry (ROTEM Ò ). Initial therapy consisted of fibrinogen concentrate (Haemocomplettan Ò P), as maximum clot firmness in the ROTEM analyses was low, whereas clotting time was normal. Later on, prothrombin complex concentrate was given to optimise thrombin generation. This approach enabled extended emergency hemihepatectomy to be performed without using fresh frozen plasma. As the EXTEM maximum clot firmness showed good clot quality, no platelets were transfused despite low platelet counts. This case shows the potential success of treatment using both fibrinogen concentrate and prothrombin complex concentrate, not only in restoring haemostasis but also in minimising requirement for transfusion of allogeneic blood products. Coagulopathy is a major challenge in trauma centres worldwide, and uncontrolled bleeding causes around 40% of all trauma-related deaths [1]. Coagulopathy is the likely cause if bleeding continues after a patient has received optimal acute surgical treatment and, if required, mechanical support to close a wound.Accurate and timely measurement of haemostatic potential is clearly needed to optimise the management of coagulopathy. Routine laboratory tests such as prothrombin time (PT) and activated partial thromboplastin time (aPTT) are widely used, although they have not been developed to guide coagulation therapy. The PT and aPTT are too slow to provide prompt results, while pathologic values in these tests are rarely associated with acute, clinically relevant bleeding. In contrast, thromboelastometry ⁄ thromboelastography support an accurate and timely assessment, not only of coagulation initiation but also the clot formation process and clot stability. A set of reagents helps evaluate different aspects of coagulation, including the stability and amplitude of the fibrin-based clot (thromboelastometric FIBTEM test). Increasingly, point-of-care methods (thrombelastography or thromboelastometry) are recognised as offering more rapid diagnosis of coagulopathy than laboratory tests [2][3][4]. Since 2001, thromboelastometry (ROTEM Ò , Pentapharm, Munich, Germany) has been used in our department as a point-of-care monitoring tool. It plays an essential role in our strategy to avoid or reverse coagulopathy in polytrauma patients.Large amounts of fresh frozen plasma (FFP) are part of treatment protocols in most trauma centres, although the efficacy of this treatment is questionable [5]. At the same time, transfusion has been associated with increased morbidity and mortality [6,7]. The risks associated with FFP include transfusion-related lung injury (TRALI), pathogen transmission [8,9] and immunosupression [10].