Tag: tranexamic acid

Categories : Injury & TraumaTags :

Shining a New Light on Tranexamic Acid for Trauma Care

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A new study from Australia, New Zealand and Germany published in the New England Journal of Medicine raises important questions about the success or otherwise of using tranexamic acid in trauma. 

Tranexamic acid is commonly used to limit bleeding during surgery. However, its usefulness in emergency settings as a pre-emptive strike in life-threatening bleeding has been controversial, and recent studies have provided contradictory results about whether or not it saves lives or causes dangerous blood clotting. 

The Pre-hospital Antifibrinolytics for Traumatic Coagulopathy and Haemorrhage (PATCH-Trauma) Study was designed to solve this dilemma. Led by Monash University and the Australian and New Zealand Intensive Care Society Clinical Trials Group, it is one of the largest clinical trials ever conducted where treatment was given at the roadside, in an ambulance or in a helicopter prior to reaching hospital. 

It involved 1310 severely injured patients treated by 15 ambulance services and 21 trauma centres in Australia, New Zealand and Germany, taking eight years to complete. 

In addition to all the usual care, patients were randomly assigned to receive pre-hospital tranexamic acid or an inactive placebo. The results showed that for every 100 patients allocated to receive tranexamic acid, there were approximately four extra survivors at six months, but all were severely-disabled and highly-dependent on carers. 

The lead investigator, Professor Russell Gruen, now Dean of the College of Health and Medicine at the Australian National University, described this as a landmark study in trauma care. “It shows it’s not enough to find out only whether treatments save lives or not – quality of life and the long-term outcomes of care also matter,” Professor Gruen said.

Monash University Professor Stephen Bernard, Medical Advisor to Ambulance Victoria and lead for the Australian arm of the study, praised the ambulance services involved. “The PATCH-Trauma Study is further proof that ambulance professionals can conduct rigorous clinical trials in very sick patients and in extremely challenging circumstances,” he said. 

As to whether tranexamic acid should be used for trauma patients, Professor Gruen is circumspect. “Because the drug needs to be given before severely injured patients can make an informed decision, further work is needed to see if we can identify patients who are more likely to survive with a favourable functional outcome if they are given tranexamic acid,” he said. “However, the PATCH-Trauma Study gives us confidence that critical care is possible well before patients get to hospital.” 

Source: EurekAlert!

Categories : Injury & TraumaTags :

Could A Perfume Ingredient Stop Coagulopathy in Massive Bleeding?

On By ModernMedia

The chances of surviving massive blood loss from a traumatic injury such as a gunshot wound are around 50%. To survive, a patient urgently needs a large infusion of blood and coagulation at the wound to stop the bleeding.

The problem is one of these solutions prevents the other. Introducing a large amount of blood to those suffering a massive haemorrhage impairs the blood’s ability to clot, a condition known as coagulopathy.  

Now, Tulane University researchers have uncovered the cause of coagulopathy in trauma victims receiving a blood infusion. They also found that a synthetic compound called dimethyl malonate – often used in perfume manufacturing – has the potential to stop coagulopathy during a massive hemorrhage. The researchers’ findings are part of a new study published in Science Advances.

“Coagulopathy of trauma is a major contributor to mortality, but no treatment has shown to be fully effective,” said Olan Jackson-Weaver, PhD, assistant professor of surgery at Tulane University School of Medicine and corresponding author on the study. “We were getting 60 percent mortality with our animal model. With dimethyl malonate, we got zero percent mortality, and the coagulopathy completely went away.”

Recent studies have shown that coagulopathy during massive haemorrhage treatment is most likely caused by the shedding of the glycocalyx, a barrier of sugars that surrounds and protects cells. In blood vessels, the glycocalyx lines the vessel walls and prevents blood from clotting. However, this is the first study to identify the cellular events that cause the glycocalyx to be ripped apart.

The study found that a large infusion of blood creates a spike in cellular metabolism which causes a change in structure to the cell membrane. This exposes the glycocalyx, allowing it to be chewed up by enzymes and mixed into the bloodstream, where it prevents clotting.

“People have been trying to figure out ways to move the needle a little bit on the death rate from massive haemorrhage for the last 20 or so years and nothing has really worked,” Jackson-Weaver said. “We’re hopeful that understanding these cellular-level events can help to develop something that actually does make a big difference.”

In animal models, dimethyl malonate was effective at inhibiting excessive cellular metabolism, which prevented the glycocalyx from shedding and causing coagulopathy.

But Jackson-Weaver said more research needs to be done to determine if dimethyl malonate is safe for humans or if an equivalent drug that targets cellular metabolism can be developed.

“We’ve established this pathway that causes coagulopathy, so if we can target it therapeutically with a pre-hospital drug or injection, we can hopefully save some lives,” Jackson-Weaver said.

Source: Tulane University

Categories : Obstetrics & GynaecologyTags :

WHO Warns of Lethal Tranexamic Acid Mix-ups in Intrathecal Administration

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Intravenous IV drip in woman's hand
Photo by Anna Shvets on Pexels

The World Health Organization is alerting health care professionals about the risk of lethal administration errors that can potentially occur with tranexamic acid (TXA) injection. There have been reports of TXA being mistaken for obstetric spinal anaesthesia used for caesarean deliveries resulting in inadvertent intrathecal administration.

Intrathecal TXA is a potent neurotoxin and neurological sequelae are manifested, with refractory seizures and 50% mortality. The profound toxicity of intrathecal TXA was described in 1980. In a 2019 review, Patel et al. identified 21 reported cases of inadvertent intrathecal injection of TXA since 1988, of which 20 were life-threatening and 10 fatal. It appears that mortality risk is greater after caesarean delivery. Sixteen were reported between 2009 and 2018.

WHO recommends early use of intravenous TXA within three hours of birth in addition to standard care for women with clinically diagnosed postpartum haemorrhage (PPH) following vaginal births or caesarean section. TXA should be administered at a fixed dose of 1g in 10 ml (100 mg/ml) IV at 1 ml per minute, with a second dose of 1g IV if bleeding continues after 30 minutes. In South Africa, the incidence of maternal bleeding after caesarean delivery has been characterised as a national emergency, and obstetric haemorrhage remains the third most common cause of maternal mortality at 17%.

However, problems can arise as TXA is frequently stored in close proximity with other medicines, including injectable local anaesthetics indicated for spinal analgesia (eg, for caesarean section). The presentation of some of the local anaesthetics is similar to the TXA presentation (transparent ampoule containing transparent solution), which can be administered in error instead of the intended intrathecal anaesthetic, and resulting in serious undesirable adverse effects.

Obstetricians from several countries have recently reported inadvertent intrathecal TXA administration and related serious neurological injuries. In a South African clinical alert, Bishop et al. highlighted the different appearances of TXA used in state and private hospitals, with one example in private hospitals appearing very similar (white label, red text) at first glance to spinal bupivacaine and stored in the same container. Applicable recommendations were provided by the authors.

TXA is a lifesaving medicine, however, this potential clinical risk should be considered and addressed by all operating theatre staff. Reviewing of existing operating theatre drug handling practice is required in order to decrease this risk, such as storage of TXA away from the anaesthetic drug trolley, preferably outside the theatre.

Source: World Health Organization

Categories : Obstetrics & GynaecologyTags :

Tranexamic Acid Cuts Blood Loss in Myomectomies

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Photo by Piron Guillaume on Unsplash

The use of tranexamic acid (TXA) reduced blood loss during myomectomies in women with large uterine fibroids, a retrospective cohort study has found.

Patients who underwent a myomectomy to remove uterine fibroids with a total weight greater than 173 g had lower estimated blood loss after receiving TXA compared with those who did not (205.6 mL vs 405.4 mL), reported Rachel Cullifer, MD, at the virtual American Association of Gynecologic Laparoscopists (AAGL) annual meeting. Furthermore, patients whose largest fibroid was greater than 73 mm had lower levels of blood loss with TXA (229.2 mL vs 408.3 mL).

“TXA is a highly safe hemostatic agent that gynecologic surgeons can utilize during myomectomies,” Cullifer said. “There is a role for TXA in myomectomies performed with a minimally invasive approach,” she added, noting that the treatment should be strongly considered for patients suspected of having a large fibroid burden.

When looking at all myomectomies not stratified by fibroid characteristics, there was not no significant difference in estimated blood loss between patients who received TXA and those who did not (184 mL vs 266 mL). Fibroids are the primary indication for hysterectomy in the US, Dr Cullifer noted, but myomectomy provides a safe alternative for those who want to preserve their fertility.

“Despite advances in laparoscopic techniques, blood loss and blood transfusions still remain higher in myomectomies when compared with hysterectomy,” Dr Cullifer pointed out, adding that elevated plasmin levels during surgery can result in prolonged bleeding. TXA lowers plasmin function and productivity, reducing blood loss, she stated.

Dr Cullifer and colleagues focused on fibroid characteristics to find out which patients might benefit most from TXA.

The researchers analysed patients who had a myomectomy from 2015 to 2020, compared myomectomy cases treated with TXA versus those that were not, and measured estimated blood loss, blood transfusion administration, and operative time. Of the 71 patients who had a myomectomy, 26 received TXA and 45 did not. The average estimated blood loss was 236 mL, and almost all patients underwent minimally invasive procedures, with 53% undergoing laparoscopic surgery and 40% undergoing robot-assisted procedures.

Save for age, all demographic characteristics were similar between the two groups. Patients who received TXA were an average of two and a half years younger than those who did not. Fibroid characteristics were also similar between the two groups. Additionally, adverse events were similar between the two groups. There was one case of thromboembolism in the cohort who did not receive TXA.

Source: MedPage Today

Categories : Injury & TraumaTags :

Positive Safety Evaluation for Tranexamic Acid

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A large meta-analysis upheld the safety of tranexamic acid (TXA), even at higher doses.

TXA is an antifibrinolytic agent with a short half-life that is used for bleeding prevention and treatment, as in causes of trauma with open wounds. Current TXA is applied with caution due to perceived increased risk of seizures, MI, and other thrombotic complications.

The meta-analysis looked at 216 randomised trials involving 125 550 participants. The investigators found that the incidence of thromboembolic events, which included venous thrombosis, pulmonary embolism, venous thromboembolism, myocardial infarction (MI) or ischaemia, and cerebral infarction or ischaemia, was 2.1% of people receiving IV TXA and a similar 2.0% of peers getting placebo or another control, which was a non-significant difference.

TXA’s safety was inconclusive in those with neurological conditions, who showed increased heterogeneity and asymmetry in funnel plots, according to Patrick Meybohm, MD, of University Hospital Wuerzburg in Germany, and colleagues.

The review confirmed that TXA was linked to a significant reduction in overall mortality and bleeding mortality, but not nonbleeding mortality.

“The results of this study suggest that use of intravenous TXA may have utility in all medical fields, with some uncertainty for patients with neurological conditions,” the investigators concluded.

“Notably, we did not detect any dose-dependent association of TEs [thromboembolic events],” they stated. The included studies had participants with IV TXA administration at doses ranging 0.5-5g or 10-100mg/kg.

“There is little doubt that when used appropriately in the various patient populations evaluated with randomized clinical trials, TXA is effective. However, reasonable questions about thrombotic complications remain,” wrote John Holcomb, MD, of University of Alabama at Birmingham, and colleagues, in an invited commentary.

“Further research must focus on how to identify, as early as possible, the patients most likely to benefit from administration of TXA,” they urged.

One limitation mentioned by the investigators was the inclusion trials that evaluated thromboembolic events without ultrasound, so asymptomatic cases may have been excluded. Furthermore, many studies did not provide much information on thrombosis prophylaxis.

For Holcomb’s group, study’s main caveat was that it included “a notably heterogeneous population”, including a range of demographics and clinical conditions. Since the pooled studies were not “clinically homogeneous”, they violated “one of the cardinal tenets of systematic reviews and meta-analyses.”

Source: MedPage Today

Journal information (primary article): Taeuber I, et al “Association of intravenous tranexamic acid with thromboembolic events and mortality: a systematic review, meta-analysis, and meta-regression” JAMA Surg 2021; DOI: 10.1001/jamasurg.2021.0884.

Journal information (commentary): Holcomb JB, et al “Tranexamic acid and safety in the right patient” JAMA Surg 2021; DOI: 10.1001/jamasurg.2021.0929.