Disseminated intravascular coagulation with a fibrinolytic phenotype at an early phase of trauma predicts mortality

Sawamura, Atsushi; Hayakawa, Mineji; Gando, Satoshi; Kubota, Nobuhiko; Shinoda, Masahiro; Wada, Takeshi; Katabami, Kenichi

doi:10.1016/j.thromres.2009.06.034

Cited by 164 publications

(172 citation statements)

References 23 publications

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“…The CRASH-2 trial underscored the central role of fibrinolysis in ATC by demonstrating a one-third reduction in death due to haemorrhage in trauma patients given tranexamic acid (TXA), which inhibits activation of plasminogen to plasmin [36,37]. Other clinical studies have reported that fibrinolytic activation is correlated with transfusions [38] and mortality [38][39][40][41][42]. The plasmin-antiplasmin complex (PAP) is perhaps the most sensitive indicator of fibrinolytic activation, and its levels are increased in approximately 60% of trauma patients [43].…”

Section: Pathophysiologymentioning

confidence: 99%

“…A net production of PAI-1 over t-PA further leads to shutdown of fibrinolysis [4,25,45]. This may explain why antifibrinolytic treatment at this stage may worsen outcome [40].…”

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confidence: 99%

“…In some ways, the initial changes of ATC are similar to DIC [40,64]. However, in most trauma patients, there is no evidence of inappropriate disseminated clot formation on histological examination [65], so early ATC is not DIC.…”

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confidence: 99%

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The pathogenesis of traumatic coagulopathy

2014

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SummaryOver the last 10 years, the management of major haemorrhage in trauma patients has changed radically. This is mainly due to the recognition that many patients who are bleeding when they come in to the emergency department have an established coagulopathy before the haemodilution effects of fluid resuscitation. This has led to the use of new terminology: acute traumatic coagulopathy, acute coagulopathy of trauma shock or trauma‐induced coagulopathy. The recognition of acute traumatic coagulopathy is important, because we now understand that its presence is a prognostic indicator, as it is associated with poor clinical outcome. This has driven a change in clinical management, so that the previous approach of maintaining an adequate circulating volume and oxygen carrying capacity before, as a secondary event, dealing with coagulopathy, has changed to haemostatic resuscitation as early as possible. While there is as yet no universally accepted assay or definition, many experts use prolongation of the prothrombin time to indicate that there is, indeed, a coagulopathy. Hypoxia, acidosis and hypothermia and hormonal, immunological and cytokine production, alongside consumption and blood loss, and the dilutional effects of resuscitation may occur to varying extents depending on the type of tissue damaged, the type and extent of injury, predisposing to, or amplifying, activation of coagulation, platelets, fibrinolysis. These are discussed in detail within the article.

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Section: Pathophysiologymentioning

confidence: 99%

“…A net production of PAI-1 over t-PA further leads to shutdown of fibrinolysis [4,25,45]. This may explain why antifibrinolytic treatment at this stage may worsen outcome [40].…”

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confidence: 99%

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The pathogenesis of traumatic coagulopathy

2014

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“…8 Similar results were recorded in a 2009 study from Japan that measured fi brin degradation product and D-dimers in 314 severe trauma patients. 10 If this early increased fi brinolysis exacerbates bleeding and increases the risk of death, then we might expect that an antifi brinolytic drug such as tranexamic acid would be most eff ective in this period.…”

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confidence: 99%

“…However, patients in the late phase of trauma can develop thrombotic disseminated intravascular coagulation, and antifi brinolytics could be contraindicated in this period. 10,11 Although disseminated intravascular coagulation is characterised by fi brin formation and coagulation, the rapid consumption of coagulation proteins can lead to their exhaustion, resulting in uncontrolled bleeding. The need to avoid giving an antifi brinolytic in this late phase was why we restricted trial inclusion to patients who were within 8 h of injury.…”

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The importance of early treatment with tranexamic acid in bleeding trauma patients: an exploratory analysis of the CRASH-2 randomised controlled trial

et al. 2011

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The importance of early treatment with tranexamic acid in bleeding trauma patients: an exploratory analysis of the CRASH-2 randomised controlled trialThe CRASH-2 collaborators* SummaryBackground The aim of the CRASH-2 trial was to assess the eff ects of early administration of tranexamic acid on death, vascular occlusive events, and blood transfusion in trauma patients with signifi cant haemorrhage. Tranexamic acid signifi cantly reduced all-cause mortality. Because tranexamic acid is thought to exert its eff ect through inhibition of fi brinolysis, we undertook exploratory analyses of its eff ect on death due to bleeding.Methods The CRASH-2 trial was undertaken in 274 hospitals in 40 countries. 20 211 adult trauma patients with, or at risk of, signifi cant bleeding were randomly assigned within 8 h of injury to either tranexamic acid (loading dose 1 g over 10 min followed by infusion of 1 g over 8 h) or placebo. Patients were randomly assigned by selection of the lowest numbered treatment pack from a box containing eight numbered packs that were identical apart from the pack number. Both participants and study staff (site investigators and trial coordinating centre staff ) were masked to treatment allocation. We examined the eff ect of tranexamic acid on death due to bleeding according to time to treatment, severity of haemorrhage as assessed by systolic blood pressure, Glasgow coma score (GCS), and type of injury. All analyses were by intention to treat. The trial is registered as ISRCTN86750102, ClinicalTrials.gov NCT00375258, and South African Clinical Trial Register/Department of Health DOH-27-0607-1919.Findings 10 096 patients were allocated to tranexamic acid and 10 115 to placebo, of whom 10 060 and 10 067, respectively, were analysed. 1063 deaths (35%) were due to bleeding. We recorded strong evidence that the eff ect of tranexamic acid on death due to bleeding varied according to the time from injury to treatment (test for interaction p<0·0001). Early treatment (≤1 h from injury) signifi cantly reduced the risk of death due to bleeding (198 Interpretation Tranexamic acid should be given as early as possible to bleeding trauma patients. For trauma patients admitted late after injury, tranexamic acid is less eff ective and could be harmful.Funding UK NIHR Health Technology Assessment programme, Pfi zer, BUPA Foundation, and J P Moulton Charitable Foundation. IntroductionThe CRASH-2 trial showed that administration of tranexamic acid to adult trauma patients with, or at risk of, signifi cant haemorrhage, within 8 h of injury, signi fi cantly reduces all-cause mortality (relative risk [RR] 0·91, 95% CI 0·85-0·97; p=0·0035) with no apparent increase in vascular occlusive events.1 As a consequence of this trial, tranexamic acid has been incorporated into trauma treatment protocols worldwide.Results from the CRASH-2 trial raise some important questions. The trial was motivated by the evidence that tranexamic acid reduces bleeding in patients undergoing elective surgery, and the hypothesised mechanism was inhi...

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