The Diagnosis and Treatment of Acute Traumatic Bleeding and Coagulopathy
Background: Uncontrolled bleeding with trauma-induced coagulopathy (TIC) is still the most common avoidable cause of death in multiple trauma. The aging of the population has led to an increasing number of bleeding trauma patients with pre-existing anticoagulation. Such patients are not treated uniformly, even in major trauma centers.
Methods: This review is based on a selective search of the literature (Medline/PubMed, Cochrane Reviews) and summarizes current treatment recommendations, including those of the newly revised European trauma guidelines.
Results: The treatment of traumatic hemorrhage begins at the site of the accident, with compression, tourniquets, pelvic binders, and rapid transport to a certified trauma center. The early use of tourniquets was shown to lessen the transfusion requirement (packed red blood cells: 2.0 ± 0.1 vs. 9.3 ± 0.6; p < 0.001; fresh frozen plasma concentrates: 1.4 ± 0.08 vs. 6.2 ± 0.4; p < 0.001), while external pelvic stabilization was shown to reduce mortality (19.1% vs. 33.3%). Upon the patient’s arrival in the hospital, steps are taken to measure, monitor, and support clotting function. Bleeding is controlled surgically according to the principles of damage control. Modern clotting management consists of goal-oriented, individualized therapy, including the use of point-of-care viscoelastic test procedures. Idarucizumab can be used as an antidote to the thrombin inhibitor dabigatran, andexanet alpha as an antidote to factor Xa inhibitors.
Conclusion: The evidence-based treatment of patients with hemorrhage from severe trauma, in accordance with the existing guidelines, can improve the clinical outcome. Corresponding algorithms, adapted to local logistics and infrastructure, must be developed and implemented.
In spite of improvements in the care of trauma patients, uncontrolled bleeding with coagulopathy as a complication remains a relevant clinical problem (1) and the most common avoidable cause of death after polytrauma (2). Death by bleeding out occurs rapidly—at a median of 1.65 hours after hospital admission (3)—and one in every four patients with severe trauma presents at admission to the shock room with laboratory-defined signs of coagulopathy (4). Systemic clotting problems may already be present at admission to the shock room or they may develop thereafter and rapidly get worse (5, 6). The therapeutic focus is on identifying acute bleeds and systemic clotting problems early and treating them in a targeted manner (7, 8). In the context of a subgroup analysis of the PROPPR study in the USA, each 15-min reduction of the time needed to control the bleed/correct the coagulopathy was associated with lowered mortality (relative risk [RR]: 0.97; 95% confidence interval [0.94; 0.99] and multiorgan failure (RR 0.94; [0.91; 0.97] (e1). The clinical care of bleeding trauma patients with accompanying coagulopathy is inconsistent, even in large trauma centers (e2-e4), although implementation of and adherence to standardized algorithms are associated with a better treatment result (e5-e7). The present article summarizes the current understanding of the pathophysiology and the recently updated treatment recommendations for the control of traumatic bleeding including complicating clotting problems.
This review article is based on a selective search of the recent literature in the databases Medline (PubMed) and Cochrane Reviews, using different combinations of the relevant search terms (“bleeding/hemorrhage,” “coagulopathy,” “management,” “mortality,” “outcome,” “transfusion,” “trauma”). Because of the topicality of the subject we considered primarily publications from the past 5 years. Additionally we considered the recently revised and updated European guideline on the management of major bleeding and coagulopathy following trauma: fifth edition (ET-GL 2019  with level of recommendation by number and level of evidence by character [recommendation / evidence level 1A–2C]). The recommendations given below follow the classification of Guyatt and colleagues with regard to their evidence levels (9).
Mechanisms of acute trauma-induced coagulopathy
Although coagulopathy in the context of traumatic injuries was initially understood as a secondary development, more recent data indicate an independent, multifactorial, and primary entity (5, 6, 10). The updated German clinical practice guidelines on the treatment of polytrauma/severe injuries now acknowledge trauma-induced coagulopathy (TIC) as an independent pathology with a notable effect on survival (7). Figure 1 shows the current concept for the pathophysiological understanding of TIC. Especially systemic endotheliopathy, triggered by hemorrhagic shock and systemic inflammation, is now considered to be a central pathophysiological element (5, 6, 11). Initial thrombin deficiency is usually not present in a bleeding trauma patient (12). Platelet function defects have recently moved into the scientific focus (e8, e9). Plasma concentrations of most clotting factors fall only slowly during acute hemorrhages and are often—even in a scenario of halved plasma volume—still within their reference ranges. By contrast, fibrinogen as a substrate of the clotting process decreases significantly as early as during the prehospital treatment phase, depending on the severity of the injury, and is the first factor to reach critical concentrations (16). Fibrinogen concentrations lowered as a result of trauma have been measured in the prehospital setting and consistently found to be associated with increased mortality and a poor treatment result at hospital admission (17). Further administration of fluids will trigger the fatal triad of existing coagulopathy, hypothermia, and acidosis.
Prehospital measures to control traumatic bleeding
The treatment of traumatic bleeding and associated coagulopathy, including TIC, starts at the site of the accident (18). Depending on the extent of blood loss, the classic ABCDE scheme may well have to be abandoned and control of the C component (circulation/critical bleeding) prioritized even before securing the airway, in the sense of a modified C-ABCDE scheme (eTable). Adequate therapeutic options are available to control external bleeding, whereas internal bleeding can often not be managed during prehospital care. In such cases, immediate transport prioritization with rapid surgical intervention in hospital is the only reasonable option that holds any hope of success (19). The crucial prehospital measures for the treatment and control of critical traumatic bleeding are summarized in the left column of Table 1. In this setting, manual and direct compression of the wound surface and/or supplying blood vessels is the most important measure in achieving timely control of the bleeding (R2/1A). If the source of the bleeding is deep within the injured tissue, the wound should be packed with sterile dressing materials. In some cases, compression is combined with physically acting hemostatics or drugs to stabilize clotting.
Although wound compression should be preferred primarily, the use of tourniquets is a proven means of controlling severe bleeding from injuries of the extremities (R2/1B). The primary use of tourniquets is especially useful in life-threatening hemorrhage or multiple sources of bleeding on one limb, if the source of the bleeding is not accessible, if concomitant and critical A, B, or C problems arise, and in the context of a mass event with multiple casualties (18). The tourniquet should be applied under sufficient analgesia in as distal a position as possible, but at least a hand width proximal to the injury, and it should be kept tight until the bleeding ceases; the time of application should be documented. If indicated and appropriately applied, the use of a tourniquet was associated with improved stability of the circulation at admission to the shock room (BPsyst 120 ± 2 vs 112 ± 2 mm Hg, p = 0.003), a reduced need for transfusion (packed red blood cells [pRBC]: 2.0 ± 0.1 vs 9.3 ± 0.6, p < 0.001; fresh frozen plasma concentrates [FFP]: 1.4 ± 0.08 vs 6.2 ± 0.4, p < 0.001), and a non-increased risk for complications, e.g., nerve injuries and infections (e10).
With increasing severity of the overall injury, rates of complex pelvic injuries with bleeding mostly from the venous peritoneal plexus increase; only 10–15% of all pelvic bleeds are arterial (e11, e12). The use of pelvic binders has been found to be an effective measure to control bleeding in complex and unstable fractures of the pelvic ring (R2/1B). If these are applied correctly at the level of both trochanters, the pelvic volume is reduced and counterpressure to the bleed is established (eFigure). The patient’s trouser pockets should be emptied before the binder is applied, and the patient’s pulse should be monitored distally before and after application. Patients with initial pelvic stabilization by means of a pelvic binder subsequently required fewer blood transfusions (2462 ± 2215 mL vs. 4385 ± 3326 mL; p<0.01), spent fewer days in the acute setting and in intensive care (16.11 ± 12.54 vs. 19.55 ± 26.14 days and 5.33 ± 5.42 vs. 8.36 ± 11.52 days), and displayed a positive trend in terms of survival (e13). In a retrospective analysis of 104 hemodynamically unstable trauma patients with relevant single injury of the pelvis, external stabilization was undertaken in 45.2% of cases (e14). In the group receiving external pelvic stabilization, 19.1% of patients died, whereas mortality in the group not receiving external stabilization was 33.3%. In view of the low sensitivity and specificity of manual checks for pelvic stability, the indication for applying a binder should be defined generously. Severe bleeding in the oromaxillofacial region, especially in the context of falls or physical violence, can be controlled either by compressing the nostrils—in most cases, more effectively by packing—or, in case of emergency, by using blocked bladder catheters (18). The prehospital administration of blood products depends on the context, risks, and logistical challenges (e15–e18). In a retrospective analysis of >55 000 US military datasets from the Iraq and Afghanistan conflicts (2001–2017), a reduction in mortality by 44% over time was associated primarily with three key interventions (e19):
- Application of tourniquets
- Reduction of prehospital transport time to less than 60 min
- Early use of blood products
Treatment in specialized centers
A white paper of the German Trauma Society (Deutsche Gesellschaft für Unfallchirurgie, DGU) set out recommendations for the structure, organization, and equipment for the care of severely injured patients in Germany, and their implementation was initiated in the context of the project TraumaNetwork DGU (20). The ET-GL 2019 recommends the direct admission of bleeding trauma patients to an appropriate trauma center (R1/1B). The TraumaNetwork DGU ensures the vertical transfer after primary stabilization in a trauma center providing a basic level of care. If a bleeding trauma patient’s circulation cannot be stabilized during the prehospital phase then the measures at the site of the accident will have to be discontinued in favor of immediate transport to a suitable trauma center (18), in order to keep the interval between injury and control of bleeding as short as possible (R1/1A). To prevent further blood loss, permissive hypotension with systolic target pressures of 80–90 mm Hg (mean target pressure 50–60 mm Hg) in patients without traumatic brain injury is an option until bleeding is controlled (R12/1C). In patients with traumatic brain injury, mean arterial pressure ≥ 80 mm Hg is recommended in order to compensate for the cerebral perfusion pressure (R12/1C). Volume replacement in hypotensive and bleeding trauma patients still consists of isotonic balanced crystalloids (R15/1A); in life-threatening bleeding and shock, administration of vasopressors should be considered to achieve the target pressure (R14/1C).
Acute management of bleeding at the trauma center
Clinical assessment and immediate surgical treatment
The extent of traumatic bleeding should be assessed by using a combination of clinical assessment of the patient’s physiology at admission, the anatomical injury pattern, and the mechanism of the injury suffered (R4/1C). The Advanced Trauma Life Support (ATLS) classification of hemorrhagic shock has limitations regarding risk stratification (e20), but has been upgraded in the latest edition of the manual by the inclusion of base deficit as an additional criterion (21, 22). The bolus response to defined fluid administration in the context of “permissive hypotension” up to control of the bleeding is subject to criticism (R13/1B). The importance of imaging methods to detect free fluids in thorax and abdomen as well as to locate possible bleeding sources is still emphasized (FAST ultrasound [R7/1C], contrast-enhanced whole-body computed tomography [R7/1B]). Patients with an obvious bleeding source and patients in severe hemorrhagic shock and a suspected bleeding source should immediately be put through a procedure to control the bleeding (R5/1C), employing the usual damage control methods (T18/1B) with closure and stabilization of the pelvic ring (R19/1B) and packing (T20/1B). The assumption is that around 10% of extremely severely injured patients will benefit from this approach; there are no individual predictive factors for therapeutic success (e21). Where the relevant infrastructure exists, angiographic embolization techniques should be considered (R20/1B); to gain time under extreme conditions in life-threatening pelvic bleeding, retrograde endovascular balloon occlusion of the aorta (REBOA) is an option until definitive care can be given (R20/2C).
Early diagnosis of coagulopathies
Targeted measures to establish, monitor, and support the clotting function should be initiated immediately after hospital admission (R23/1B). Initially lowered hemoglobin can be used as an indicator for a severe hemorrhage with accompanying coagulopathy (R8/1B); repeated measurements are required, however, since an initial result within the reference levels can mask an existing hemorrhage (R8/1B). Sensitive parameters for the establishment and monitoring of shock depth and severity of the bleed are lactate and base deficit (BD) (R9/1A). The routine diagnostic work-up for coagulopathies should—because of their dynamics—be undertaken early and repeated at short intervals, taking account of the standard variables of clotting function (prothrombin time [PT; Quick], platelet count, and fibrinogen concentration) and/or point-of-care PT/international normalized ratio (INR) (R10/1C) and/or functional viscoelastic testing methods (R10/1C). For the first time, the updated European trauma guidelines consider the standard parameters of clotting function and viscoelastic testing as equivalent during diagnostic evaluation (8). By using the latter, the functional clotting properties of the patient’s blood in terms of formation, firmness, and dissolution of the clot can be documented at the bedside, providing a relevant time advantage (e22, e23). In suspected platelet dysfunction, additional point-of-care approaches are recommended to investigate platelet function (R11/2C).
Acute coagulation-stabilizing treatment
Acute treatment in a setting where a massive transfusion is to be expected includes on the one hand the empirical administration of FFP and pRBC at a predefined ratio of at least 1:2 (R24/1C) in the sense of the damage control resuscitation (DCR) concept or, alternatively, administration of fibrinogen concentrate and pRBC (R24/1C). These strategies should, as early as possible, give way to a targeted and individualized therapeutic concept, guided by the usual (above-mentioned) standard parameters of clotting function or on the basis of viscoelastic testing (R25/1B). Regarding the latter, studies have shown a positive trend in terms of survival and also a reduction in the need for allogenic blood products (23). In contrast to the conventional standard parameters of clotting function (Quick/INR and aPTT) limited to the initiation phase and minimum thrombin generation, viscoelastic testing yields immediate treatment-relevant information about the dynamics and sustainability of the clot structure and stability, including (hyper-)fibrinolysis. Viscoelastic testing can be carried out in the shock room/operating theater with no delay, and the results can immediately be considered in the therapeutic decision (24). Figure 2 shows the current recommendations for guiding treatment with coagulation-stabilizing substances and blood products in bleeding trauma patients, using POC rotational thrombelastometry (ROTEM) on the basis of consensus-based thresholds (24). In the course of clotting management based on FFP, the use of FFP should be guided by the standard parameters PT and aPTT (>1.5 of normal) and/or viscoelastic signs of a lack of clotting factors (R26/1C). Giving FFP to patients without massive hemorrhages (R26/1B) or to treat hypofibrinogenemia is expressly not recommended (R26/1C). In consideration of the standard values, the threshold for fibrinogen substitution is ≤ 1.5 g/L as measured according to Clauss (R28/1C).
The recommendation based on the CRASH-2 trial is early use of the antifibrinolytic tranexamic acid (TXA) in bleeding trauma patients or in the presence of a risk for significant hemorrhage: TXA should be given as a bolus within 3 h after the injury (1 g intravenously over 10 min), followed by an infusion (1 g over 8 h) (R22/1A). Administration of TXA can be considered even before transfer to the hospital (R22/1C). Substitution of clotting factor XIII to stabilize the clot can be considered, but currently no detailed recommendations exist (R27/2C). The use of recombinant factor VIIa as first-line treatment is not recommended (R31/1B); it can be considered if bleeding continues despite the deployment of the listed and conventional strategies and after correction of acidosis, temperature, fibrinogen level, and platelet count (R31/2C). The threshold values for transfusion of pRBC with an Hb target value of 7–9 g/L (R16/1C) and platelet concentrates with a target of > 50 × 109/L (R29/1C), or > 100 × 109/L in sustained bleeding or traumatic brain injury (R29/2C), remain valid. It is self-evident that acidosis and hypothermia should be avoided (R17/1C) and that monitoring and correction of lowered calcium concentrations should be performed in the context of a massive transfusion (R30/1C). The crucial immediate measures to control the bleeding and stabilize coagulation in the setting of shock room treatment are summarized in the right-hand column of Table 1.
Bleeding trauma patients receiving anticoagulation
Demographic change means that the number of bleeding trauma patients who are taking anticoagulant drugs can be expected to rise (25). If previous treatment is known or suspected, laboratory chemical screening (R10/1C) is recommended, and in the case of a sustained bleed it is advised to neutralize the effects (R32/1C). Although the anticoagulant effect of vitamin K-dependent antagonists can be detected by measuring the INR and can be neutralized by emergency administration of prothrombin complex concentrates (PCC) and oral vitamin K (R33/1A), the current trend is towards prescribing direct and non-vitamin K-dependent oral anticoagulants (apixaban, dabigatran, edoxaban, and rivaroxaban) in the setting of various underlying cardiological and neurological disorders. In the setting of acute bleeding emergencies, idarucizumab is an antidote for the thrombin inhibitor dabigatran (5 g intravenously [R35/1B]), and clotting activity levels can be estimated by using thrombin time ([R35/2C] for the qualitative estimate), ecarin clotting time, and diluted thrombin time [R35/2C]) (25); factor-Xa inhibitors (apixaban, edoxaban, and rivaroxaban) by using calibrated chromogenic anti-factor-Xa activity tests (R34/2C) (25). These methods are not universally available, react differently depending on the anticoagulant in use, and often do not detect the entire therapeutic range, so that demonstration of presence and neutralization of effects remain a challenge, especially in the emergency setting (25). In the event of life-threatening bleeding in patients treated with factor-Xa inhibitors, the recommended treatment is TXA 15 mg/kg (or 1 g) intravenously and PCC (25–50 units/kg) (R34/2C).
In March 2019 the European Medicines Agency (EMA) recommended approval of the factor-Xa antidote andexanet alfa; the substance has been available in Germany since 1 September 2019. Sustained bleeding in patients treated with platelet function inhibitors and in documented inhibition should be treated with platelet concentrates (R36/2C); this should be considered in particular in patients with intracranial bleeds who require neurosurgery (R36/2B). Administration of desmopressin can also be considered (R36/2C). Close collaboration with a hemostaseologist is strongly advised. Table 2 summarizes the current recommendations for dealing with anticoagulants in the context of bleeding trauma patients.
Adherence to ethical guidelines
For this article, the author did not undertake studies in humans or animals. For the cited studies, the respective reported ethical guidelines apply.
Conflict of interest statement
Marc Maegele has received lecture honoraria, fees for participating in expert and advisory panels, and financial funding for participating tin conferences and undertaking scientific projects from Abbott Laboratories, Astra Zeneca, Bayer, Biotest, CSL Behring, IL-Werfen/TEM-International, LFB Biomedicaments France, and Portola.
Manuscript received on 13 June 2019, revised version accepted on
6 September 2019
Translated from the original German by Birte Twisselmann, PhD
Prof. Dr. med. Marc Maegele
Klinik für Orthopädie, Unfallchirurgie und Sporttraumatologie
Klinikum Köln-Merheim, Kliniken der Stadt Köln gGmbH
Institut für Operative Medizin (IFOM)
Ostmerheimer Str. 200
51109 Köln, Germany
Cite this as:
Maegele M: The diagnosis and treatment of acute
traumatic bleeding and coagulopathy. Dtsch Arztebl Int 2019; 116: 799–806. DOI: 10.3238/arztebl.2019.0799
► Supplementary material
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