Tag: deep vein thrombosis

Scientists ‘Poke the Bear’ to Gain a Better Understanding of Blood Clotting

Photo by Mark Basarab on Unsplash

It’s generally good advice not to “poke the bear” as they say, but that’s exactly what a multinational team of scientists have been doing, to discover the secrets of blood clotting. Hibernating bears, paralysed humans, and pigs kept in small enclosures all avoid dangerous blood clots, despite being immobile for extremely long periods.

Their new study published in Science shows that reduction of a key protein inhibits the formation of blood clots in all three mammal species when they are immobile for days, months or even years.

Passengers on long haul flights run the risk of developing deep vein thrombosis if they do not take some time to walk around and use compression socks. Some people are predisposed to blood clots, due to genetic factors.

Yet, when humans – and other mammals such as bears – are immobilised for a much longer period than a flight, the researchers found that a protein known as Hsp47 is reduced by 55 times. This could lead to new medicines to help those who have inherited blood clotting disorders that put them at risk for pulmonary embolism, heart attack, and stroke.

Professor Jon Gibbins led the work at the University of Reading. He said: “It seems counterintuitive that people who have severe paralysis don’t appear to be at higher risk of blood clots. This tells us that something interesting is happening. And it turns out that reducing levels of Hsp47 plays a key role in preventing clots, not just in humans, but in other mammals, including bears and pigs.

“When we see something like this in multiple species, that reinforces its importance. Having Hsp47 must have been an evolutionary advantage.”

Hsp47 is released by platelets – the sticky blood cells that trigger blood clotting.  Usually clotting is an important response to an injury, to prevent blood loss, and Hsp47 is one of the necessary ingredients to enable platelets to do their job. Examining the role of Hsp47 in clotting function the team found that when released into the blood of bears, mice and humans that it promoted conditions that may give rise to deep vein thrombosis.

Professor Gibbins said, “We aren’t totally sure how, but it appears that there is something about movement that keeps Hsp47 at an appropriate level. It could be that the mechanical forces involved in moving around actually have an impact on gene expression, dramatically increasing the amount of Hsp47 that circulates in the blood.”

The team took blood samples from bears in winter, while hibernating, and in summer, while awake and moving around. They also compared people who were immobilised with those who can move and walk. And finally, pigs kept in small pens were compared with others that were free to move around in barns. In all three cases, proteomics experiments showed that the absence of movement was associated with having far less Hsp47.

Professor Gibbins continued: “Now we know that Hsp47 is so important, we can begin to look for new or existing medicines that might be able to inhibit the function of this protein in blood clotting and protect mobile people who are prone to clots.”

Source: University of Reading

Aspirin as Effective as Heparin for Clot Prevention in Bone Fracture Hospitalisation

Source: Mat Napo on Unsplash

Patients hospitalised with fractures typically receive low-molecular-weight heparin to prevent life-threatening blood clots. A new clinical trial, however, found that inexpensive over-the-counter aspirin is just as effective. The findings, published today in the New England Journal of Medicine, may lead surgeons to change their practice and administer aspirin to these patients.

With more than 12 000 patients, the multi-centre randomised clinical trial is the largest trial ever conducted on orthopaedic trauma patients. This multidisciplinary collaboration between orthopaedic surgeons and trauma surgeons points to the importance of evaluating techniques used to prevent post-surgical complications, like blood clots and infections, through high-quality, head-to-head comparison studies.

“Many patients with fractures will likely strongly prefer to take a daily aspirin over receiving injections after we found that both give them similar outcomes for prevention of the most serious outcomes from blood clots,” said the study’s principal investigator Robert V. O’Toole, MD. “We expect our findings from this large-scale trial to have an important impact on clinical practice that may even alter the standard of care.”

Patients who experience fractures that require surgery are at increased risk of developing blood clots, including life-threatening pulmonary embolisms. Current guidelines recommend prescribing low-molecular-weight heparin (enoxaparin) to prevent these clots, although smaller clinical trials in total joint replacement surgery suggested a potential benefit of aspirin as a less-expensive, widely available option.

The study enrolled 12 211 patients with leg or arm fractures that necessitated surgery or pelvic fractures regardless of the treatment. Half were randomised to 30mg of injectable enoxaparin twice daily. The other half received 81mg of aspirin twice daily. Patients were followed for 90 days to measure health outcomes from the two treatments.

The main finding of the study was that aspirin was “non-inferior,” or no worse than low molecular-weight heparin in preventing death from any cause – 47 patients in the aspirin group died, compared with 45 patients in the heparin group. For other important complications, the researchers also found no differences in pulmonary embolisms between the two groups. The incidence of bleeding complications, infection, wound problems, and other adverse events from the treatments was also similar in both groups.

Of all the outcomes studied, the only potential difference noted was in deep vein thrombosis. This condition was relatively uncommon in both groups as it occurred in 2.5% of patients in the aspirin group, and in 1.7% of patients in the heparin group.

“This relatively small difference was driven by clots lower in the leg, which are thought to be of less clinical significance and often do not require treatment,” said study co-principal investigator Deborah Stein, MD, MPH.

“Many patients don’t like giving themselves injections. It’s not fun in terms of giving the actual injection because it burns, and your stomach tends to bruise more easily compared to aspirin,” said Debra Marvel, a 53-year-old from Columbia, MD, who served as a patient advisor on the study. She received Lovenox (low-molecular-weight heparin) after her legs were crushed in a 2015 pedestrian accident, requiring multiple surgeries at the University of Maryland Shock Trauma Center. “Patients also prefer aspirin because Lovenox can be expensive based on insurance.”

“An estimated one million Americans are hospitalised each year with extremity fractures, and this new finding could help prevent potentially fatal blood clots in these patients using a medication that is cheaper and far easier to administer,” said Mark T. Gladwin, MD, Vice President for Medical Affairs, University of Maryland, Baltimore, and the John Z. and Akiko K. Bowers Distinguished Professor and Dean, University of Maryland School of Medicine. “Given these important results, we can expect the guidelines for the prevention of blood clots to be revised to include the option of aspirin for patients with traumatic bone fractures.”

Source: University of Maryland School of Medicine