Case Scenario: Management of Trauma-induced Coagulopathy in a Severe Blunt Trauma Patient

COAGULOPATHY-RELATED diffuse bleeding, which is complex and difficult to manage, is observed in around 20–30% of all severe trauma patients.1,2 Its management remains critical to patient survival; however, the optimal approach to treatment remains a matter of debate.3 Early recognition and adequate aggressive management of this Trauma-induced Coagulopathy (TIC) has been shown to substantially reduce mortality and improve outcomes in severely injured bleeding patients.3,4 To date, the use of fresh frozen plasma (FFP) is an integral part of massive transfusion protocols in most trauma centers and its early use has been advocated.2–4 Moreover, the use of FFP is associated with well-established risks such as multiple organ failure or transfusion-related acute lung injury (TRALI), and there is insufficient evidence to guide the optimal use of this resource.5–7 To overcome these weaknesses, several European authors advocate the use of fibrinogen concentrates and/or prothrombin complex concentrates (PCC),4,8 with preliminary clinical studies suggesting an increased efficiency based on biological parameters and a reduction of mortality.9,10 Hence, recent European guidelines recommend the use of fibrinogen concentrates and suggest increasing the fibrinogen target level to 1.5–2.0 g/l.3The purpose of this case scenario is to identify key points essential for the treatment of TIC.A 26-yr-old man, without significant medical history and weighting around 100 kg, sustained a severe motorbike collision. He was initially admitted to a general hospital after being transported by a fire rescue team. On the first clinical examination, the patient was hemodynamically stable and alert. X-rays showed multiple fractures (open humerus and closed femur diaphysis, wrist). A whole-body computed tomography showed a traumatic rupture of the aortic arch, a bilateral pulmonary contusion with small hemothorax, a renal contusion, and multiple pelvic fractures (left acetabulum, and bilateral inferior and superior ramus of the pubic bone) without contrast extravasation. Progressively the patient became hemodynamically unstable, 3 units of packed erythrocytes were given together with 1 g of tranexamic acid (TXA, 10 mg/kg) and 1000 ml hydroxyethyl starch (Voluven®, Fresenius, Germany). Pelvic stabilization was done with a pelvic belt (SAM Pelvic Sling II, SAM Medical Products, Tualatin, OR). General anesthesia was induced after rapid sequence induction, with etomidate and succinylcholine, and mechanical ventilation was started. General anesthesia was maintained with an association of midazolam and sufentanyl. The patient was therefore sent to our trauma center. During helicopter transport, hemodynamic control had necessitated both fluid infusion (normal saline and Voluven® [1000 ml]) and continuous infusion of norepinephrine (1 mg/h). One gram of TXA was also injected during the transport.At admission, patient’s hemodynamic status was as follows: systolic blood pressure, 110 mmHg; heart rate, 100 beats/min. Because of the absence of severe traumatic brain injury, norepinephrine was immediately decreased to 0.5 mg/h to reduce blood loss. The initial admission hemoglobin was 9.7 g/dl and the International Normalized Ratio determined by the Coaguchek® (Roche, Meylan, France) was 0.9. Despite the results of the Coagucheck®, rotational thromboelastometry (ROTEM®, Tem International GmbH, Munich, Germany) showed a typical pattern of coagulopathy with decreased clot amplitude on EXTEM (fig. 1A) and FIBTEM (fig. 1B), suggesting, respectively, an increase in prothrombin time (PT) and a decrease in fibrinogen level. Twenty U/kg of PCCs (2000 U, Kanokad®, LFB Laboratoire, Courtaboeuf, France) and 45 mg/kg of fibrinogen (4.5 g, Clottafact®, LFB Laboratoire) were therefore administered to the patient and resulted to the correction of coagulation abnormalities on EXTEM (fig. 1C) and FIBTEM channels (fig. 1D).Laboratory parameter analysis from blood sample drawn at admission subsequently confirmed the coagulopathy (fibrinogen, 1.1 g/l; PT, 18 s; platelets, 102,000/ml) which was associated with a moderate metabolic acidosis (lactate, 3.1 mm; base excess, −6.3). Interestingly, it should be observed that the results of blood sample analysis done at admission were available only after completion of the second ROTEM® analysis. As observed with the ROTEM® analysis, hemostasis parameters improved with the administration of factor concentrates (fibrinogen, 2.2 g/l; PT, 14.8 s).The patient was taken to the operating room for plate fixation of left humerus and intramedullary femur nailing. Two orthopedic surgeons did the procedures simultaneously to reduce surgery time, as part of the damage control surgery principle. During orthopedic surgery, an additional 2 packed erythrocytes units were given together with 669 ml of blood saver restitution (Cell Saver 5, Haemonetics, Braintree, MA) and 1 g of TXA. Then, after a period of stabilization and rewarming in the postanesthesia care unit, the patient was sent to the cardiac surgery unit and a stent was inserted in the aortic arch (Medtronic Valiant, Santa Rosa, CA).No platelet administration or additional blood product was necessary during the first 24 h. Platelet count remained always up to 100,000/ml. Blood gas analysis which was repeated by 2 h during the first 12 h showed that metabolic acidosis remained moderate (maximum lactate level, 5.0 mm and maximum base excess, −8.2).Thromboembolism prophylaxis was started on day 2 with enoxaparin (40 mg/day). Extubation was done on day 5 and he was transferred to the ward the days after. No thromboembolic complication was observed during the course. The patient was finally discharged from the hospital to a rehabilitation care unit on postinjury day 28.Severe trauma with direct injury to major blood vessels and organs can induce hypovolemic shock and exsanguination if treatment is not provided immediately. The genesis of TIC is complex and multifactorial.1,2,11 It involves initially an endogenous coagulopathy (acute traumatic coagulopathy) resulting from the combination of tissue trauma and systemic hypoperfusion, characterized by systemic anticoagulation and hyperfibrinolysis, putatively through endothelial activation of protein C.12,13 Acidosis and hypothermia with dilution induced by fluid resuscitation contribute to a further impairment of coagulation that will exacerbate the acute traumatic coagulopathy, resulting in TIC (fig. 2).2,11,14One of the key challenges during the management of trauma remains the early recognition of TIC.2 Urgent diagnostic and therapeutic decisions are often necessary to avoid multiorgan failure resulting from prolonged hemorrhagic shock.3,4 In addition to the vital signs (arterial pressure and heart rate) and visual estimation of blood loss, these decisions often require serial measurements of blood coagulation parameters to react promptly to persistent or recurrent bleeding. Clinically, the treatment of coagulopathic bleeding is compromised by current coagulation monitoring test that can take from 45 to 60 min.15 The entire blood volume of the bleeding patient may have been exchanged several times during this time interval, making the results of the laboratory test obsolete. Different point-of-care devices have been developed to rapidly determine PT (and/or International Normalized Ratio, Coaguchek®, INRatio® [Alere, San Diego, CA]),12,15 or to describe viscoelastic continuous profiles of whole blood clot formation by utilizing the ROTEM® (Tem International GmbH) or the TEG® (Haemonetics Corp.; fig. 3).16,17 Point-of-care PT can help in the triage process; however, the potential for false-negative results remains, as described in the case section.12,15 ROTEM® and TEG® both utilize the principles of thrombelastography. The primary difference between instruments is that the TEG® operates by moving a cup filled with blood in a limited arc. This blood engages a pin/wire which transduces the increase in viscosity as clot formation occurs. The ROTEM®, on the contrary, has an immobile cup containing blood. Here, the pin/wire oscillates and captures the changing viscosity with clotting.11 The computer-processed signal from either thrombelastography is presented as a tracing of clot formation (figs. 3 and 4). The two instruments can identify accurately coagulopathic patients early, often within 5 min.12,17 Hence, in coagulopathic patients, ROTEM® analysis shows that 5 min after activating coagulation with tissue factor (EXTEM) or inhibiting platelets with cytochalasin D (FIBTEM), clot amplitude is decreased and coagulation time is increased (fig. 1) compared to a normal tracing (fig. 4). Good correlation has been shown between standard coagulation parameters and ROTEM® or TEG® parameters; for example, between the clot amplitude at 15 min (EXTEM) and the PT or the fibrinogen level and the amplitude of the clot (FIBTEM) at 10 min.16 ROTEM® and TEG® may also be effective in predicting the need for massive transfusion.12,17In addition to global coagulation parameter monitoring, it is now also possible with the ROTEM® or the TEG® to specifically target coagulation defects that have been traditionally difficult to quantify at the bedside, including hyperfibrinolysis (fig. 5), or a fibrinogen deficit.18,19 However, it should be mentioned that according to a recent report, the TEG® (using kaolin) was not able to distinguish coagulopathies caused by dilution from that caused by thrombocytopenia.20TIC is observed in up to 30% of severe trauma patients at admission in the trauma bay and increases mortality.1,2 Early correction of TIC is, therefore, an important goal of the resuscitation process together with the correction of the other components of the lethal triad (i.e., hypothermia and acidosis). Recent European guidelines emphasize the need for early diagnosis of TIC together with rapid correction through early replacement of FFP and platelets, with specific recommended targets for hemoglobin, platelets, PT, and fibrinogen (table 1).3Regarding platelet transfusion, European guidelines recommend that platelets be administered to maintain a platelet count above 50 × 109/l and suggest maintaining a platelet count above 100 × 109/l in patients with multisystem trauma who are severely bleeding.3 Recent studies have concluded that platelet transfusion decreases mortality during massive transfusion and that a high ratio of platelet to packed erythrocytes was correlated with improved survival.21Recent military and civilian experiences indicate that for patients requiring massive transfusion, an initial plasma (P) to erythrocytes (E) unit ratio (P:E ratio) approaching 1:1 is independently associated with improved survival.2–5,22 However, most of the data are derived from retrospective studies that have missing data and analytical biases, limiting the conclusions that can be drawn from these results.6,23 The most important source of bias comes from the impact of survival because patients who survive are more likely to receive FFP than patients who die, creating an artifactual association of survival with higher P:E ratios.6,23 A very recent work, however, suggests that the observed mortality benefit associated with high component transfusion ratios is unlikely owing to survivor bias and that early attainment of high transfusion ratios may significantly lower the risk of mortality in patients receiving massive transfusion.22 These data support the importance of immediate recognition of patients with TIC, patients who can then benefit from an early and massive transfusion.FFP administration exposes patients to side effects, including increased susceptibility to infection, transfusion-associated circulatory overload, transfusion-related immunomodulation, and TRALI.5,6 In the United Kingdom, the Serious Hazards of Transfusion (SHOT) database documented 162 cases of TRALI over an 8-year study period including 36 deaths and 93 cases of major morbidity, and identified TRALI as the most prominent cause of transfusion-related morbidity and mortality.24 FFP from female donors has been particularly implicated in the pathogenesis of TRALI, and antileukocyte antibodies are found in 15–17% of female donors and 25% of multiparous donors but are rare in male donors.25 To reduce this risk, blood centers have adopted policies to produce plasma components primarily from male donors.26 Increasing the aggressive use of emergency plasma replacement also leads to the transfusion of ABO nonidentical units. These adverse events can be observed in all patients receiving FFP, and not only in those receiving a massive transfusion.27 In trauma patients specifically, a similar negative outcome was seen with exposure to ABO nonidentical plasma being associated with increasing complications including acute respiratory distress syndrome and sepsis.28Acting quickly is critical because coagulopathy appears immediately after trauma at the site of the injury.29 The efficacy of plasma transfusion plays out in the first few hours of resuscitation, and there is a temporal relationship between aggressive plasma transfusions and survival.30 Reducing the delay to transfusion requires the implementation of massive transfusion protocols, which incorporate local agreements with blood banks and trauma packs. As FFP is not immediately available due to the thawing process, other solutions have to be considered.31 Thawed AB group or low titer group A which can be for 5 and plasma immediate of plasma in the first trauma by immediate thawing of FFP for the centers will maintain a plasma immediate to the of data the use of high the of these will also need to be in to the possible resuscitation to these injured patients within the The goal of increasing the ratio is to use component to to whole blood in to rapidly or avoid of coagulopathy during the initial resuscitation of an of massive transfusion protocols, than treatment based on the of leads to early of blood which may in a more rapid control of The use of a massive transfusion had been to a decrease in blood product use and mortality with of blood immediate of blood is based on immediately available factor concentrates has been more approach to the correction of TIC has been by a few European specific coagulation factor concentrates according to identified by fibrinogen concentrates and are in several European for the treatment of and and have been given with to trauma and in other is a key protein for hemostasis and clot During fibrinogen is by and acidosis fibrinogen hypothermia fibrinogen and hydroxyethyl starch infusion of fibrinogen is, therefore, of the first blood components to decrease to early during the of trauma fibrinogen is recommended in patients with massive bleeding to maintain plasma fibrinogen above 1.5–2.0 may be administered as a part of a massive transfusion administration of 3 g 50 mg/kg) after erythrocytes based on standard laboratory results or by as a part of early coagulation to control by increasing clot use of has been for use in trauma is a of and to and to the of In the United these are as PCCs in with additional factor LFB are and clinical data suggest that PCCs may be effective in however, high level of evidence is and it is not possible to support use in clinical However, it should also be mentioned that all of the data a benefit with the use of PCCs in trauma has been done with of factor concentrates in the of trauma is because are immediately the time delay associated with and transfusion of may also be by and the potential risks associated with blood Moreover, the process at of reduction or which the risk of data from the of have that cases of have been with to an in has an important on but only on clot of has been described in association with fibrinogen concentrates with the administration of both by the ROTEM® as part of an early coagulation management (fig. this have the of TIC without FFP with In a second retrospective have that may reduce the exposure of trauma patients to blood a These data are very and support further which are necessary for the use of its complications are the major risk of The thromboembolic risk also on the of the in the between and the absence of and the of or protein and protein in have been in the have been taken the potential of these the of PCCs should the recommended by the European Medical such as the of in addition to with factor and factor and low factor and factor increase in the risk of and coagulation has been in an of hemorrhagic shock high of were The between and may be for these that were not observed standard of U/kg were the of has been this time, the most effective for the management of TIC remains It is that the of coagulation factor replacement and early diagnosis of factor are is in severe trauma and is to the of injury and of In to a a is which may in cases fig. such as is effective in a clot that is to However, clot of may be because may also a in coagulation through the of prothrombin to activation of and the of on In have also been with which therefore is to multiple organ failure or acid is a of the that by the on It blood in patients with both normal and to surgery and has been for more than for blood in In the of an in has that if given early TXA mortality in trauma of the patients were not severely injured or bleeding, making the of the study difficult to However, with of more than patients in this TXA as an effective treatment for traumatic It should be observed that the reduction of mortality to bleeding was than and there were significant in transfusion between suggesting of other than on as In a recent described the use of TXA in a of in the study was the authors found in patients receiving at unit of erythrocytes an association of TXA with survival on Moreover, the benefit was more prominent in patients requiring massive In addition to the of these TXA is and in these a thromboembolic complication the ratio is in of given during the first 3 h after a during the factor a for or bleeding in patients with has been for trauma However, its efficacy with to mortality outcomes has been It is also and may patients to an increased risk for A by who that the administration of was shown to reduce blood product administration with an of the thromboembolic risk should be in the management of primarily in all to control bleeding have and and is not a for the aggressive use of blood first goal of this is to bleeding by the of or As severe trauma patients not prolonged effective control is with the of damage control surgery initial by procedures immediately after surgery is after the patient has been in the care second is to reduce further and organ was to fluid infusion and then to reduce coagulopathy and hypothermia as as all the events to aggressive resuscitation with including acute respiratory distress multiple organ and However, if the and of and that can be a target systolic pressure of is in the absence of severe brain injury, bleeding is goal is to the which the TIC, including and the dilution of after administration of and for these may improve trauma a normal is a effective to improve hemostasis during massive an important in coagulation and a higher than 30% may be to starch solutions induce coagulopathy caused by fibrinogen The clinical of this side remains but should be hydroxyethyl starch is within in hemodynamically plasma a volume with high and coagulation for comes from the management of trauma patients the that specifically target either factor or use is recommended for after surgery, such as as as for the treatment of pulmonary and for the of and systemic in The first with use comes from the absence of an to quantify the anticoagulation level. monitoring is not in clinical such as bleeding, or the anticoagulation level may be laboratory are as a to determine normal from coagulation or to the of the in time and/or the time suggest the of a normal time out the of a of in a but be to the an that plasma has been developed and may an optimal for plasma this is not of an available to the of these is of to trauma and emergency the only is emergency for However, a rapid in severely injured and bleeding patients remains, in the most trauma a In this it is that 2 h of will of with or a severe trauma should receive the bleeding resuscitation, including FFP is also likely to the of coagulation according to a recent is for the The use of coagulation has been including and induced a decrease in the bleeding time in or but it not the of the PCCs have been shown to the in who but did not the time or time in who In a recent study suggests that factor and to be able to the of and However, there is study the of these coagulation in the bleeding the use of PCCs will be effective in critical bleeding in this remains to be with case not only the by which coagulopathy in a patient with severe but also the of diagnosis and treatment of have seen the of for the rapid of hemostasis which not only the early diagnosis of TIC but also the of which specific component is in the coagulopathic is the fibrinogen which can be with the ROTEM® or the However, it remains to be that the use of this point-of-care will improve outcomes or in a reduction of blood the therapeutic level, will have to with studies that a high ratio is associated with an in outcome without increase in adverse events such as TRALI or In a of two blood product ratios the Platelet and has been and is in the process of In to avoid potential adverse events to these blood but also because the of blood product is European authors have specific coagulation These coagulation (fibrinogen, prothrombin and are immediately available with a very of these may decrease the specific adverse to the use of blood However, evidence and small clinical studies are available with clinical studies are Because of a risk of thromboembolic complication coagulation are will be in these will have to on the of early diagnosis of coagulopathy together with the use of both factor concentrates and/or high