Tag: thrombin

Categories : Cardiovascular DiseaseTags :

Intensive Blood Pressure Reduction after Ischaemic Stroke Increases Disability

On By ModernMedia
Credit: American Heart Association

The largest ever randomised controlled trial of intensive blood pressure lowering after thrombectomy in ischaemic stroke patients found that it led to deterioration in surrounding brain tissue and higher rates of disability, compared to less intensive treatment.

The results of the ENCHANTED2/MT trial were presented in a late-breaking session at the World Stroke Congress and simultaneously published in The Lancet. The trial was stopped early due to the significance of the findings.

Professor Craig Anderson, Director of Global Brain Health at The George Institute for Global Health, said the rapid emergence of this effect suggested the more aggressive approach was compromising the return of blood flow to the affected area.

“Our study provides a strong indication that this increasingly common treatment strategy should now be avoided in clinical practice,” he said.

Endovascular thrombectomy is an increasingly used non-surgical treatment for ischaemic stroke, in which x-ray guided microcatheters are inserted into the blood clot to dissolve it.

“A potential downside of this now widely used and effective treatment is that the rapid return of blood supply to an area that has been deprived of oxygen for a while can cause tissue damage known as reperfusion injury,” said Professor Anderson.

“This has resulted in a shift in medical practice towards more intensive lowering of blood pressure after clot removal to try and minimise this damage, but without evidence to support the benefits versus potential harms.”

To this end, researchers recruited 816 adults with acute ischaemic stroke who had elevated blood pressure after clot removal from 44 centres in China between July 2020 and March 2022. They had an average age of 67 and just over a third were female.

Of these, 407 were assigned to more-intensive (target < 120mmHg) and 409 to the less-intensive (target 140–180mmHg) systolic blood pressure control, with the target to be achieved within one hour of entering the study and sustained for 72 hours.

Researchers looked at how well the patients in both groups recovered according to a standard measure of disability, ranging from 0–1 for a good outcome without or with symptoms but no disability, scores of 2–5 reflecting increasing disability levels, and 6 being death.

Patients in the more-intensively treated group had significantly worse scores on the scale compared to those allocated to those treated less intensively.

Compared to the less-intensive group, they had more early brain tissue deterioration and major disability at 90 days but there were no significant differences in brain bleeds, mortality, or serious adverse events.

Patients who had their blood pressure more intensively controlled also rated their quality of life as significantly worse due to limitations on their physical abilities resulting from their stroke.

Prof Anderson said that after scouring the medical literature the research team had been unable to find strong enough evidence to recommend the ideal target for blood pressure control after blood clot removal in patients with acute ischaemic stroke.

“While our study has now shown intensive blood pressure control to a systolic target of less than 120mmHg to be harmful, the optimal level of control is yet to be defined,” he said.

Source: George Institute for Global Health

Categories : Medical Research & TechnologyTags :

Thrombin’s Involvement with Coagulation Reconsidered

On By ModernMedia
Source: NIH

After 20 years of research, an established truth of how thrombin interacts with coagulation has been overturned.

“It has been said that an established truth in medicine lasts for about 10 years. It is probably the case that many truths last longer, but on the other hand, the time that different truths stand is constantly shrinking. This is because our perception of reality is changing rapidly, in step with new research,” said Tom Eirik Mollnes, Professor at the University of Oslo and Oslo University Hospital.

Based on more than 20 years of work to develop a whole blood model, Mollnes and colleagues have recently disproved an established truth about the immune system.

“There was an established truth in the literature for many years that a protein in the coagulation system called thrombin could activate a protein called C5 in the complement system,” Prof Mollnes said.

However, Prof Mollnes and his colleagues doubted whether the methods used in the studies were reliable.

“The notion that the protein thrombin could activate the protein C5 was only shown in so-called purified systems. That is, the proteins were taken out of their natural context,” he explained.

The researchers thought that the results would possibly be different if you looked at how the proteins work in their natural environment in the blood.

“The modified model made it possible to study the connection between the various proteins and defence systems as close to reality as possible,” Prof Mollnes explained. “Using the new model, we clearly showed that the previous findings were incorrect. We showed that the proteins changed structure and function during the purification, and that this was the reason for the former findings.”

When the proteins were in their natural environment in the blood, thrombin did not activate the protein in the complement system. Thus, the researchers had disproved the established truth.

“Many findings have been published in purified systems that are not representative of reality,” he said. “You can say that Gro Harlem Brundtland’s statement that “everything is connected to everything” is a very good description of how biology and the human body work. Therefore, it is important to use methods that make it possible to look at how different systems in the body interact and cooperate.”

The whole blood model makes such methods possible, and the model can be used widely. The whole blood model can, by and large, be used to study all the substances and biological systems in the blood.

Professor Mollnes therefore considers the model to have great potential.

“With the whole blood model, we have contributed to something that we will not only benefit from in our own laboratory, but that can be an asset to research groups in a number of fields,” he said.

It takes time to develop new models, and it was a long uphill battle for Prof Mollnes and his research group. Even so, the researchers have now received recognition for their work from the research community. The article got a recommendation by the editors of The Journal of Immunology, [PDF] in which it was published, as a ‘Top Reads Selection’.

“Changing so-called established truths is not easy, and we had to go through many rounds, with a number of experiments, to gain acceptance for our findings. That is why our work was especially recognised,” he concluded.

Source: University of Oslo