Effects of a high-dose 24-h infusion of tranexamic acid on death and thromboembolic events in patients with acute gastrointestinal bleeding (HALT-IT): an international randomised, double-blind, placebo-controlled trial (2020)

Type of publication:
Randomised controlled trial

The HALT-IT Trial Collaborators (including *John Jones and *Charlotte Owen)

Lancet, 2020; Vol. 395: pp. 1927–36

Background: Tranexamic acid reduces surgical bleeding and reduces death due to bleeding in patients with trauma. Meta-analyses of small trials show that tranexamic acid might decrease deaths from gastrointestinal bleeding. We aimed to assess the effects of tranexamic acid in patients with gastrointestinal bleeding.
Methods: We did an international, multicentre, randomised, placebo-controlled trial in 164 hospitals in 15 countries. Patients were enrolled if the responsible clinician was uncertain whether to use tranexamic acid, were aged above the minimum age considered an adult in their country (either aged 16 years and older or aged 18 years and older), and had significant (defined as at risk of bleeding to death) upper or lower gastrointestinal bleeding. Patients were randomly assigned by selection of a numbered treatment pack from a box containing eight packs that were identical apart from the pack number. Patients received either a loading dose of 1 g tranexamic acid, which was added to 100 mL infusion bag of 0·9% sodium chloride and infused by slow intravenous injection over 10 min, followed by a maintenance dose of 3 g tranexamic acid added to 1 L of any isotonic intravenous solution and infused at 125 mg/h for 24 h, or placebo (sodium chloride 0·9%). Patients, caregivers, and those assessing outcomes were masked to allocation. The primary outcome was death due to bleeding within 5 days of randomisation; analysis excluded patients who received neither dose of the allocated treatment and those for whom outcome data on death were unavailable. This trial was registered with Current Controlled Trials, ISRCTN11225767, and ClinicalTrials.gov, NCT01658124.
Findings: Between July 4, 2013, and June 21, 2019, we randomly allocated 12 009 patients to receive tranexamic acid
(5994, 49·9%) or matching placebo (6015, 50·1%), of whom 11952 (99·5%) received the first dose of the allocated
treatment. Death due to bleeding within 5 days of randomisation occurred in 222 (4%) of 5956 patients in the
tranexamic acid group and in 226 (4%) of 5981 patients in the placebo group (risk ratio [RR] 0·99, 95% CI 0·82–1·18).
Arterial thromboembolic events (myocardial infarction or stroke) were similar in the tranexamic acid group and
placebo group (42 [0·7%] of 5952 vs 46 [0·8%] of 5977; 0·92; 0·60 to 1·39). Venous thromboembolic events (deep vein
thrombosis or pulmonary embolism) were higher in tranexamic acid group than in the placebo group (48 [0·8%] of
5952 vs 26 [0·4%] of 5977; RR 1·85; 95% CI 1·15 to 2·98).
Interpretation: We found that tranexamic acid did not reduce death from gastrointestinal bleeding. On the basis of our
results, tranexamic acid should not be used for the treatment of gastrointestinal bleeding outside the context of a
randomised trial.

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Three-Year delayed presentation of femoral pseudoaneurysm after penetrating limb trauma (2015)

Type of publication:
Journal article

Butterworth J.W., *Butterworth W.A., Wu R.

Annals of Vascular Surgery, February 2015, vol./is. 29/2(362.e11-362.e15)

Background Delayed presentations of lower limb pseudoaneurysms secondary to penetrating trauma are particularly rare. Methods After presentation of this rare case report, we review relevant published literature. Results We report a rare case of a 55-year-old man with a progressively enlarging mass measuring 15 cm by 15 cm on his right anteromedial thigh 3 years after penetrating trauma. Computer tomography angiogram revealed this to be a large pseudoaneurysm supplied by a side branch artery from the right superficial femoral artery. Using an open approach, the pseudoanerysm was successfully repaired with the side branch oversewn, and the patient made a good recovery being discharged from hospital 4 days later. Conclusions Surgeons must retain pseudoaneurysm as a prominent differential for a patient presenting with a progressively enlarging, expansile mass of an extremity after penetrating trauma to ensure urgent investigation and prompt vascular intervention. Both open surgical ablation and endovascular embolization of pseudoaneurysms of the extremities are effective techniques with low rates of complications and morbidity reported in published literature.


Use of a massive haemorrhage protocol in a UK district general hospital is associated with a reduction in mortality (2014)

Type of publication:
Conference abstract

Lambert L.,Taylor B.,Alistair W.

Intensive Care Medicine, September 2014, vol./is. 40/1 SUPPL. 1(S208), 0342-4642 (September 2014) (also published in Anaesthesia, June 2014, vol./is. 69/(118), 0003-2409 (June 2014))

INTRODUCTION. Massive haemorrhage is associated with significant morbidity and mortality. In the context of major trauma managed in a large centre, the use of a massive haemorrhage protocol emphasizing early haemostatic resuscitation reduces mortality (1). However, it is not clear if these models are effective in non-trauma patients (2). There is some concern that these protocols may increase the wastage of blood products which might be a concern in smaller hospitals. (3) OBJECTIVES. To audit the activation of and compliance with a massive haemorrhage protocol in a UK district general hospital. To assess if compliance with the protocol resulted in a difference in mortality, morbidity, length of ICU stay, or use of blood products. METHODS. Retrospective audit over 12 months analyzing the case notes of all patients who had suffered a massive haemorrhage against a massive haemorrhage protocol which emphasizes early haemostatic resuscitation. RESULTS. The protocol was activated in 9 patients, but unfortunately notes were unavailable for one as he was undergoing outpatient treatment. A further 9 patients were identified as having had a massive transfusion, without activation of the protocol, from blood bank data as having been issued emergency uncrossmatched group O blood, or having had more than 10 units of any blood products in a 24 h period. Where a massive haemorrhage protocol was used, 1/8 patients (12.5 %) died. Where a major transfusion was conducted without activation of the protocol, 7/9 patients died (77.8 %). This finding was statistically significant (p = 0.0152) using a 2-tailed fishers exact test. Fewer units of red cells (p = 0.0011) and FFP (p = 0.0034) were used in patients managed according to the protocol, but there was no difference in the use of platelets or cryoprecipitate. Two patients in the group where the protocol had not been activated were given cryoprecipitate despite normal fibrinogen levels, and a further two in this group were not given cryoprecipitate despite fibrinogen levels under 1 g/l CONCLUSIONS. Use of a massive haemorrhage protocol which focuses on rapid haemorrhage control, haemostatic resuscitation and early use of blood is associated with a lower mortality than management of major bleeds without the protocol. This appears to apply in predominantly non-trauma patients in a non-specialist centre. This was a retrospective audit, and the group in whom the protocol was not activated had a higher expected mortality, therefore the results warrant further research.

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