Major trauma is the sixth leading cause of death worldwide and the fifth leading cause of moderate and severe disability; in Europe, major trauma is the third cause of death after cardiovascular diseases and tumours. Bleeding is the first avoidable cause of death within the first 24 hours since a traumatic event, and it is the cause of death of about 40% of all trauma mortality. About 25-30% of MT patients present some degree of coagulation alteration in the very first phases after the traumatic event. Trauma Induced Coagulopathy (TIC) is a clinical syndrome caused by imbalance among clotting, anticoagulation, and fibrinolysis resulting from multiple pathological factors such as hemorrhage and tissue injury in the early stages of trauma; it can occur prior to treatment and is to be considered as a physiological consequence to major trauma. We conducted a prospective, monocentric, observational study of all patients referred to the Department of Emergency and Acceptance, IRCCS Fondazione Policlinico San Matteo, Pavia, for MT in 13 consecutive months (1 January 2018 - 30 January 2019), of which the primary focus was investigating TIC. All patients referred to the ER and registered in the hospital’s MT registry were enrolled (n°=503). This Thesis focuses on the following four findings which emerged from the gathered data, with particular attention on the first and second point: 1) The correlation between a greater number of body districts involved by the traumatic event and TIC development (p=0.000). We report 47% of the patients of Group 1 (with TIC) having three or more body districts involved compared to 23% of Group 2 (without TIC); in the current literature ISS is correlated with TIC, but there unfortunately seems to lack specificity about the exact number of body districts involved in trauma patients with multiple injuries developing TIC; nevertheless, we are confident that continuing researching the correlation between number of body districts involved by the traumatic event and TIC development will clarify our findings. 2) The correlation between head trauma and TIC development (p=0.000). Head trauma is identified as an independent risk factor for TIC and several studies also suggest low GCS as an independent risk factor. Unfortunately the exact mechanism is yet poorly understood, and albeit significant gaps remain in defining the possible pathophysiological pathways leading from brain injury to coagulopathy, progress has been made in understanding them, specifically it is reported that tissue factor rich neurological tissues play a role in TIC development. 3) The correlation between abdominal trauma and TIC development (p=0.057). Albeit further testing is needed to confirm the independent correlation between abdominal trauma and coagulopathy, our results suggest the possibility of such a link; in the reviewed literature this correlation has recently been brought forward also from a 2017 independent study by Derakhshanfar et al.; the presence of coagulopathy in abdominal trauma patients has proven significant enough to warrant several studies aimed at limiting or halting its development and improve our treatment procedures by including suggestions of coagulopathy management protocols. 4) The correlation between male sex and TIC development (p=0.018). The exact nature of this correlation requires greater depth of research to be determined, albeit several studies report similar clinical evidence, one of which suggesting sex hormones to play a role in the matter. It would be interesting to gather more gender-specific data, taking also into account menopausal state and exogenous hormone use, but given the dynamically life-threatening nature of the acute traumatic setting, it is understandable how difficult it is to conduct such in-depth studies on this possible correlation.
Il trauma maggiore è la sesta causa di morte nel mondo; in Europa, i traumi maggiori sono la terza causa di morte dopo le malattie cardiovascolari e i tumori. Il sanguinamento è la prima causa di morte evitabile entro le prime 24 ore da un evento traumatico ed è la causa di morte di circa il 40% di tutta la mortalità da trauma. Circa il 25-30% dei pazienti con trauma maggiore presenta un certo grado di alterazione della coagulazione nelle primissime fasi successive all'evento traumatico. La coagulopatia relata al trauma è una sindrome clinica causata da uno squilibrio tra coagulazione, anticoagulazione e fibrinolisi derivante da molteplici fattori patologici quali emorragia e lesioni tissutali nelle prime fasi del trauma; può verificarsi prima del trattamento ed è da considerarsi come conseguenza fisiologica di un trauma grave. Abbiamo condotto uno studio prospettico, monocentrico, osservazionale di tutti i pazienti indirizzati al Dipartimento di Emergenza e Accettazione, IRCCS Fondazione Policlinico San Matteo di Pavia, per trauma maggiore della durata di 13 mesi consecutivi (1 gennaio 2018 - 30 gennaio 2019), di cui il focus primario è stato studiare la coagulopatia relata al trauma. Sono stati arruolati tutti i pazienti indirizzati al pronto soccorso e registrati nel registro trauma grave dell'ospedale (n°=503). Questa Tesi si concentra sui seguenti quattro rilievi emersi dai dati raccolti: 1) La correlazione tra un maggior numero di distretti corporei coinvolti dall'evento traumatico e lo sviluppo di coagulopatia relata al trauma (p=0.000). Il 47% del Gruppo 1 (con coagulopatia) risulta avere tre o più distretti corporei coinvolti rispetto al 23% dei Gruppo 2 (senza coagulopatia); nella letteratura attuale l'ISS è correlato alla coagulopatia relata al trauma, ma sembra mancare specificità sul numero esatto di distretti corporei coinvolti in pazienti traumatizzati con lesioni multiple con coagulopatia; siamo fiduciosi che continuare a studiare la correlazione tra il numero di distretti corporei coinvolti dall'evento traumatico e lo sviluppo di coagulopatia chiarirà i nostri risultati. 2) La correlazione tra trauma cranico e sviluppo di coagulopatia relata al trauma (p=0.000). Il trauma cranico è identificato come fattore di rischio indipendente per coagulopatia e diversi studi suggeriscono anche un basso punteggio GCS come fattore di rischio indipendente. Sfortunatamente il meccanismo esatto è ancora poco compreso e, sebbene permangano lacune significative nella definizione dei possibili percorsi fisiopatologici che portano dalla lesione cerebrale alla coagulopatia, abbiamo fatto progressi nel comprenderli. 3) La correlazione tra trauma addominale e sviluppo di coagulopatia relata al trauma (p=0,057). Sebbene siano necessari ulteriori test per confermare la correlazione indipendente tra trauma addominale e coagulopatia, i nostri risultati suggeriscono la possibilità di un tale collegamento; nella letteratura recensita questa correlazione è stata recentemente portata avanti anche da uno studio indipendente del 2017 di Derakhshanfar et al.; la presenza di coagulopatia nei pazienti con trauma addominale si è dimostrata abbastanza significativa da giustificare diversi studi volti a limitare o arrestare il suo sviluppo e migliorare le nostre procedure di trattamento includendo suggerimenti di protocolli di gestione della coagulopatia. 4) La correlazione tra sesso maschile e sviluppo di TIC (p=0,018). L'esatta natura di questa correlazione richiede un maggiore approfondimento di ricerca per essere determinata, anche se diversi studi riportano simili risultati clinici, uno dei quali suggerendo che gli ormoni sessuali giochino un ruolo in materia. Sarebbe interessante raccogliere dati di genere più specifici, ma data l'innata pericolosità tempo-dipendente del trauma grave acuto, è comprensibile quanto sia difficile condurre un tale approfondimento su questa possibile correlazione.
Trauma Induced Coagulopathy: Clinical and Anatomical Findings of a Prospective Observational Study
GEROSA, SEBASTIANO
2019/2020
Abstract
Major trauma is the sixth leading cause of death worldwide and the fifth leading cause of moderate and severe disability; in Europe, major trauma is the third cause of death after cardiovascular diseases and tumours. Bleeding is the first avoidable cause of death within the first 24 hours since a traumatic event, and it is the cause of death of about 40% of all trauma mortality. About 25-30% of MT patients present some degree of coagulation alteration in the very first phases after the traumatic event. Trauma Induced Coagulopathy (TIC) is a clinical syndrome caused by imbalance among clotting, anticoagulation, and fibrinolysis resulting from multiple pathological factors such as hemorrhage and tissue injury in the early stages of trauma; it can occur prior to treatment and is to be considered as a physiological consequence to major trauma. We conducted a prospective, monocentric, observational study of all patients referred to the Department of Emergency and Acceptance, IRCCS Fondazione Policlinico San Matteo, Pavia, for MT in 13 consecutive months (1 January 2018 - 30 January 2019), of which the primary focus was investigating TIC. All patients referred to the ER and registered in the hospital’s MT registry were enrolled (n°=503). This Thesis focuses on the following four findings which emerged from the gathered data, with particular attention on the first and second point: 1) The correlation between a greater number of body districts involved by the traumatic event and TIC development (p=0.000). We report 47% of the patients of Group 1 (with TIC) having three or more body districts involved compared to 23% of Group 2 (without TIC); in the current literature ISS is correlated with TIC, but there unfortunately seems to lack specificity about the exact number of body districts involved in trauma patients with multiple injuries developing TIC; nevertheless, we are confident that continuing researching the correlation between number of body districts involved by the traumatic event and TIC development will clarify our findings. 2) The correlation between head trauma and TIC development (p=0.000). Head trauma is identified as an independent risk factor for TIC and several studies also suggest low GCS as an independent risk factor. Unfortunately the exact mechanism is yet poorly understood, and albeit significant gaps remain in defining the possible pathophysiological pathways leading from brain injury to coagulopathy, progress has been made in understanding them, specifically it is reported that tissue factor rich neurological tissues play a role in TIC development. 3) The correlation between abdominal trauma and TIC development (p=0.057). Albeit further testing is needed to confirm the independent correlation between abdominal trauma and coagulopathy, our results suggest the possibility of such a link; in the reviewed literature this correlation has recently been brought forward also from a 2017 independent study by Derakhshanfar et al.; the presence of coagulopathy in abdominal trauma patients has proven significant enough to warrant several studies aimed at limiting or halting its development and improve our treatment procedures by including suggestions of coagulopathy management protocols. 4) The correlation between male sex and TIC development (p=0.018). The exact nature of this correlation requires greater depth of research to be determined, albeit several studies report similar clinical evidence, one of which suggesting sex hormones to play a role in the matter. It would be interesting to gather more gender-specific data, taking also into account menopausal state and exogenous hormone use, but given the dynamically life-threatening nature of the acute traumatic setting, it is understandable how difficult it is to conduct such in-depth studies on this possible correlation.È consentito all'utente scaricare e condividere i documenti disponibili a testo pieno in UNITESI UNIPV nel rispetto della licenza Creative Commons del tipo CC BY NC ND.
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https://hdl.handle.net/20.500.14239/12882