Case report
Tranexamic acid use in severely injured patients, is it always appropriate?
Ácido tranexámico en el paciente politraumatizado grave, ¿está siempre indicado?
P. Duque
, L. Gonzalez-Zarco, R. Martínez, S. Gago, J.A. Varela
Corresponding author
Anestesiología, Hospital General Universitario Gregorio Marañón, Madrid, Spain
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"tieneTextoCompleto" => true "paginas" => array:1 [ 0 => array:2 [ "paginaInicial" => "301" "paginaFinal" => "303" ] ] "autores" => array:1 [ 0 => array:4 [ "autoresLista" => "P. Duque, L. Gonzalez-Zarco, R. Martínez, S. Gago, J.A. Varela" "autores" => array:5 [ 0 => array:4 [ "nombre" => "P." "apellidos" => "Duque" "email" => array:1 [ 0 => "patriduque@gmail.com" ] "referencia" => array:1 [ 0 => array:2 [ "etiqueta" => "*" "identificador" => "cor0005" ] ] ] 1 => array:2 [ "nombre" => "L." "apellidos" => "Gonzalez-Zarco" ] 2 => array:2 [ "nombre" => "R." "apellidos" => "Martínez" ] 3 => array:2 [ "nombre" => "S." "apellidos" => "Gago" ] 4 => array:2 [ "nombre" => "J.A." "apellidos" => "Varela" ] ] "afiliaciones" => array:1 [ 0 => array:2 [ "entidad" => "Anestesiología, Hospital General Universitario Gregorio Marañón, Madrid, Spain" "identificador" => "aff0005" ] ] "correspondencia" => array:1 [ 0 => array:3 [ "identificador" => "cor0005" "etiqueta" => "⁎" "correspondencia" => "Corresponding author." ] ] ] ] "titulosAlternativos" => array:1 [ "es" => array:1 [ "titulo" => "Ácido tranexámico en el paciente politraumatizado grave, ¿está siempre indicado?" ] ] "textoCompleto" => "<span class="elsevierStyleSections"><p id="par0005" class="elsevierStylePara elsevierViewall">Severe injury is associated with hypocoagulability and hyperfibrinolysis secondary to the endothelial release of activated protein C and tissue plasminogen activator (tPA), respectively. Given the risk of hyperfibrinolysis, guidelines recommend administering 1 g IV tranexamic acid as soon as possible in all patients presenting with bleeding or at risk of bleeding, and repeating the dose every 8 h (evidence 1 A).<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a></p><p id="par0010" class="elsevierStylePara elsevierViewall">We report the case of an 82-year-old man who presented with severe injuries after being hit by a bus. Upon arrival at the outpatient department, he was conscious (Glasgow 15), eupnoeic, and haemodynamically stable (BP = 140/70 mmHg, in sinus rhythm at 85 bpm). He presented catastrophic injuries to the lower left limb on which a tourniquet had been placed, but showed no signs of shock or hypoperfusion. He was given 1 g tranexamic acid, 500 ml crystalloids together with analgesic and anaesthesia induction agents. Intubation was uneventful and he was transferred to the referral hospital, where the injured limb was amputated. A Colles fracture of the left radius was also diagnosed and closed reduction was performed. After emergency surgery, a complete CT scan was performed in which a fracture was observed in the lateral wall of the left maxillary sinus with haemosinus. His injuries were therefore classified as severe, with a New Injury Severity Score (NISS) of 38. The CT scan was significant for the presence of a filling defect straddling both main pulmonary arteries and extending to the segmental branch of the left lower lobe and the segmental branch of the right upper lobe, consistent with acute pulmonary thromboembolism (PE). The patient’s medical history included hypertension and hypertensive heart disease in treatment with amlodipine and ameride. We administered thromboembolic prophylaxis with low molecular weight heparin (enoxaparin 40 mg/day subcutaneously). The patient remained stable at all times and made good progress. He was extubated the following day and transferred to the ward 3 days after the accident.</p><p id="par0015" class="elsevierStylePara elsevierViewall">Immediate PE, defined as PE diagnosed within the first 6 h, has been associated with severe trauma. It is generally asymptomatic, usually central, and rarely requires therapeutic anticoagulation.<a class="elsevierStyleCrossRef" href="#bib0010"><span class="elsevierStyleSup">2</span></a> Virchow described the classic triad that contributes to thrombosis: venous stasis, endothelial damage, and hypercoagulability. Venous stasis is unlikely to play a major role in immediate PE. However, the usual central and bilateral radiological pattern suggests an embolic origin. Endothelial activation could be assumed to be decisive, although it is striking that our patient did not present chest trauma, a characteristic in common with most of the cases described in the literature. This suggests the presence of a hypercoagulable pattern, where the determining factor is the activation of coagulation as the body's defence to life-threatening bleeding.</p><p id="par0020" class="elsevierStylePara elsevierViewall">The benefit of administering tranexamic acid in patients with severe trauma is currently a subject of debate in the literature,<a class="elsevierStyleCrossRef" href="#bib0015"><span class="elsevierStyleSup">3</span></a> since different patterns of fibrinolytic activation can occur, ranging from hyperfibrinolysis to decreased fibrinolysis, which can potentially cause a prothrombotic pattern.</p><p id="par0025" class="elsevierStylePara elsevierViewall">In 2014, Moore et al.,<a class="elsevierStyleCrossRef" href="#bib0020"><span class="elsevierStyleSup">4</span></a> defined 3 fibrinolysis profiles from a sample of 180 severe multiple trauma patients: hyperfibrinolysis, physiological fibrinolysis, and fibrinolysis shutdown. They found that fibrinolysis shutdown occurred in the majority of patients (63.8%), that mortality was higher in these patients compared with patients with physiological fibrinolysis, and that mortality was mainly due to multiple organ dysfunction, which was attributed to the deposit of small thrombi in the microcirculation. The same group obtained similar results in a much larger sample (n = 2,540). These results have been replicated in other studies in adult and paediatric multiple trauma patients. Persistence of fibrinolysis shutdown for more than 1 week increases the risk of mortality regardless of age, sex, severity and mechanism of injury.<a class="elsevierStyleCrossRef" href="#bib0025"><span class="elsevierStyleSup">5</span></a></p><p id="par0030" class="elsevierStylePara elsevierViewall">Given the existence of different fibrinolysis profiles, some authors suggest using viscoelastic methods (VEM) to guide the administration of tranexamic acid. However, one type of hyperfibrinolysis with a poor prognosis is diagnosed by increased plasmin-antiplasmin levels, and remains occult to VEM.<a class="elsevierStyleCrossRefs" href="#bib0030"><span class="elsevierStyleSup">6–8</span></a> Using VEM to guide the administration of tranexamic acid is specifically discouraged in the latest clinical guidelines,<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> and plasmin-antiplasmin tests are not available in routine clinical practice.</p><p id="par0035" class="elsevierStylePara elsevierViewall">We recently reported that severe tissue trauma can trigger a prothrombotic response aimed at stopping bleeding, and that shock and the associated adrenergic response shifts the haemostatic response from a procoagulant to a hypocoagulable and hyperfibrinolytic state, the objective of which is to maintain the patency of the microcirculation and promote tissue perfusion.<a class="elsevierStyleCrossRef" href="#bib0045"><span class="elsevierStyleSup">9</span></a> In vitro, tissue ischaemia and hypoxia of any origin cause hyperfibrinolysis.</p><p id="par0040" class="elsevierStylePara elsevierViewall">Given the existence of fibrinolysis shutdown, and that administering tranexamic acid in this situation could predispose the patient to thrombosis, in the absence of reliable clinical diagnostic methods a growing number of authors recommend restricting tranexamic acid to patients in shock.<a class="elsevierStyleCrossRefs" href="#bib0010"><span class="elsevierStyleSup">2,9,10</span></a> Following this recommendation, tranexamic acid would not have been indicated in our patient, because he did not present shock or hypoperfusion at any time (his shock index [SI] at admission was < 0.9) and did not fulfil ABC criteria for massive bleeding. However, according to recent European clinical guidelines,<a class="elsevierStyleCrossRef" href="#bib0005"><span class="elsevierStyleSup">1</span></a> tranexamic acid was indicated in our patient due to bleeding.</p><p id="par0045" class="elsevierStylePara elsevierViewall">We cannot establish a causal relationship between the administration of tranexamic acid and the appearance of acute PE. We can, however, confirm that our patient presented severe injury (NISS = 38) without shock (SI = 0.6) and with prothrombotic risk factors (lower limb injury with associated vascular injury).</p><p id="par0050" class="elsevierStylePara elsevierViewall">In conclusion, when treating a patient with severe injury with no shock or hypoperfusion, it is important to consider the possible existence of thrombophilia.</p><span id="sec0005" class="elsevierStyleSection elsevierViewall"><span class="elsevierStyleSectionTitle" id="sect0025">Conflict of interests</span><p id="par0055" class="elsevierStylePara elsevierViewall">The authors have no conflict of interest to declare.</p></span></span>" "textoCompletoSecciones" => array:1 [ "secciones" => array:6 [ 0 => array:3 [ "identificador" => "xres1526140" "titulo" => "Abstract" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abst0005" ] ] ] 1 => array:2 [ "identificador" => "xpalclavsec1383591" "titulo" => "Keywords" ] 2 => array:3 [ "identificador" => "xres1526141" "titulo" => "Resumen" "secciones" => array:1 [ 0 => array:1 [ "identificador" => "abst0010" ] ] ] 3 => array:2 [ "identificador" => "xpalclavsec1383590" "titulo" => "Palabras clave" ] 4 => array:2 [ "identificador" => "sec0005" "titulo" => "Conflict of interests" ] 5 => array:1 [ "titulo" => "References" ] ] ] "pdfFichero" => "main.pdf" "tienePdf" => true "PalabrasClave" => array:2 [ "en" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Keywords" "identificador" => "xpalclavsec1383591" "palabras" => array:5 [ 0 => "Multiple trauma" 1 => "Tranexamic acid" 2 => "Hyperfibrinolysis" 3 => "Fibrinolysis shutdown" 4 => "Pulmonary embolism" ] ] ] "es" => array:1 [ 0 => array:4 [ "clase" => "keyword" "titulo" => "Palabras clave" "identificador" => "xpalclavsec1383590" "palabras" => array:5 [ 0 => "Politraumatizado" 1 => "Ácido tranexámico" 2 => "Hiperfibrinólisis" 3 => "Fibrinólisis disminuida" 4 => "Tromboembolismo pulmonar" ] ] ] ] "tieneResumen" => true "resumen" => array:2 [ "en" => array:2 [ "titulo" => "Abstract" "resumen" => "<span id="abst0005" class="elsevierStyleSection elsevierViewall"><p id="spar0005" class="elsevierStyleSimplePara elsevierViewall">Recently, it has been suggested that tranexamic acid should be administered only in those patients with hyperfibrinolysis determined using viscoelastic assays, as severely injured patients may present with fibrinolytic shutdown. However the last European guidelines on management of major bleeding and coagulopathy following trauma endorse the use of tranexamic acid to the trauma patient who is bleeding or at risk of significant hemorrhage as soon as possible without waiting for viscoelastic results. We present a severely blunt trauma patient treated with on-scene administration of tranexamic acid that developed immediate pulmonary embolism.</p></span>" ] "es" => array:2 [ "titulo" => "Resumen" "resumen" => "<span id="abst0010" class="elsevierStyleSection elsevierViewall"><p id="spar0010" class="elsevierStyleSimplePara elsevierViewall">Recientemente se ha sugerido la administración de ácido tranexámico sólo en aquellos pacientes con hiperfibrinólisis documentada con métodos viscoelásticos, ya que los pacientes politraumatizados graves pueden presentar una disminución de la fibrinólisis. Sin embargo, las últimas guías clínicas sobre el manejo de la hemorragia y coagulopatía tras un trauma recomiendan el uso de ácido tranexámico en todo paciente sangrante, o con posibilidad de sangrar, lo más precozmente posible sin esperar los resultados de los métodos viscoelásticos. Presentamos el caso de un trauma cerrado grave que recibió ácido tranexámico prehospitalariamente y desarrolló un embolismo pulmonar inmediato.</p></span>" ] ] "NotaPie" => array:1 [ 0 => array:2 [ "etiqueta" => "☆" "nota" => "<p class="elsevierStyleNotepara" id="npar0005">Please cite this article as: Duque P, Gonzalez-Zarco L, Martínez R, Gago S, Varela JA. Ácido tranexámico en el paciente politraumatizado grave, ¿está siempre indicado? Rev Esp Anestesiol Reanim. 2021;68:301–303.</p>" ] ] "bibliografia" => array:2 [ "titulo" => "References" "seccion" => array:1 [ 0 => array:2 [ "identificador" => "bibs0005" "bibliografiaReferencia" => array:10 [ 0 => array:3 [ "identificador" => "bib0005" "etiqueta" => "1" "referencia" => array:1 [ 0 => array:2 [ "contribucion" => array:1 [ 0 => array:2 [ "titulo" => "The European guideline on management of major bleeding and coagulopathy following trauma: fifth edition" "autores" => array:1 [ 0 => array:2 [ "etal" => true "autores" => array:6 [ 0 => "D.R. Spahn" 1 => "B. Bouillon" 2 => "V. Cerny" 3 => "J. Duranteau" 4 => "D. Filipescu" 5 => "B.J. 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