Patient's question triggers important study about blood thinners

Physicians around the world now have guidance that can help them determine the best oral blood thinners to use for their patients suffering from blood clots in their veins, thanks to a patient of The Ottawa Hospital who asked his physician a question he couldn't answer. This new guidance is found in a study published today by JAMA, the Journal of the American Medical Association.

"Right there in the clinic, he identified an important knowledge gap for clinicians. We decided to act on it and find the answer," says hematologist Dr. Marc Carrier, who also a scientist at The Ottawa Hospital and associate professor at the University of Ottawa.

Dr. Carrier was treating Jamie Dossett-Mercer for major blood clotting in his leg veins, called deep vein thrombosis, that reached from his ankle to his groin. If one of these clots were to break off, it could travel to the lung and cause a pulmonary embolism, which is often fatal. These two common medical conditions are known together as venous thromboembolism and form the third leading cause of cardiovascular death.

In recent years, a number of new oral anticoagulants have been approved for use. Faced with eight possible therapies, Dossett-Mercer asked, "How do all these different blood thinners compare head to head?"

Dr. Carrier went looking for the answer. Although he found dozens of trials that studied the effect of different agents separately, none had analyzed all the results together.

His team reviewed 45 randomized trials (involving nearly 45,000 patients) using a process called network meta-analysis, which allows them to set a baseline treatment and compare all the other treatments to that. All the clinical trials they found compared the newer treatments to the standard of care, which is low-molecular-weight heparin (LMWH) with vitamin K antagonists.

Using the LMWH-vitamin K antagonist combination as the central node of the network, they compared safety and effectiveness with seven other anticoagulant therapies for venous thromboembolism: unfractionated heparin (UFH) with vitamin K antagonists; fondaparinux with vitamin K antagonists; LMWH with dabigatran; LMWH with edoxaban; rivaroxaban; apixaban; and LMWH alone.

While they found no major differences in effectiveness and safety, there were some notable variations.

• Patients taking the UFH-vitamin K antagonist combination had a higher percentage who experienced a recurrent blood clot within three months.
• Patients taking rivaroxaban and apixaban had a lower percentage who experienced a major bleeding event within three month.

"This will help physicians tailor their care according to patient characteristics," says Dr. Carrier. "For example, if I am worried about recurrent clotting, but I'm not too worried about the risk of bleeding, then I can select the drug with the best safety profile."

"I was already impressed with Dr. Carrier's exceptional care," says Dossett-Mercer. "But that he would do this research based on a patient question is just astounding."

Source: Ottawa Hospital Research Institute

Computer model predicts red blood cell flow

Rendering of stream of blood cells. Credit: © Witold Krasowski / Fotolia

Adjacent to the walls of our arterioles, capillaries, and venules -- the blood vessels that make up our microcirculation -- there exists a peculiar thin layer of clear plasma, devoid of red blood cells. Although it is just a few millionths of a meter thick, that layer is vital. It controls, for example, the speed with which platelets can reach the site of a cut and start the clotting process.

"If you destroy this layer, your bleeding time can go way up, by 60 percent or more, which is a real issue in trauma," said Eric Shaqfeh, the Lester Levi Carter Professor and a professor of chemical engineering and mechanical engineering at Stanford University. Along with his colleagues, Shaqfeh has now created the first simplified computer model of the process that forms that layer -- a model that could help to improve the design of artificial platelets and medical treatments for trauma injuries and for blood disorders such as sickle cell anemia and malaria.

The model is described in a paper appearing in the journal Physics of Fluids.

The thin plasma layer, known as the Fåhræus-Lindqvist layer, is created naturally when blood flows through small vessels. In the microcirculation, the layer forms because red blood cells tend to naturally deform and lift away from the vessel walls. "The reason they don't just continually move away from the wall and go far away is because, as they move away, then also collide with other red blood cells, which force them back," Shaqfeh explained. "So the Fåhræus-Lindqvist layer represents a balance between this lift force and collisional forces that exist in the blood."

Because the deformation of red blood cells is a key factor in the Fåhræus-Lindqvist layer, its properties are altered in diseases, such as sickle cell anemia, that affect the shape and rigidity of those cells. The new model, which is a scaled-down version of an earlier numerical model by Shaqfeh and colleagues that provided the first large-scale, quantitative explanation of the formation of the layer, can predict how blood cells with varying shapes, sizes, and properties -- including the crescent-shaped cells that are the hallmark of sickle cell anemia -- will influence blood flow.

The model can also help predict the outcome of -- and perfect -- treatments for trauma-related injuries. One common thing to do during treatment for trauma injuries is to inject saline, which among other things reduces the hematocrit, the blood fraction of red blood cells. With our model, Shaqfeh said, "we can predict how thick the Fåhræus-Lindqvist layer will be with a given hematocrit, and therefore how close the platelets will be to the periphery of the blood vessels -- and how quickly clotting will occur.

Source: American Institute of Physics (AIP)

Technique for cardiovascular diagnostics shows promise

Researcher Elira Maksuti is involved in developing and testing a promising method for diagnosing atherosclerosis, or hardening of the arteries. Credit: Staffan Larsson

A new technique developed at Sweden's KTH Royal Institute of Technology shows promise for early diagnosis and treatment of cardiovascular disease.

Hardening of the arteries, or atherosclerosis, is a common disorder that occurs when fat, cholesterol, and other substances build up in the walls of arteries and form hard structures called plaques. The condition can lead to heart attacks and strokes.

To diagnose atherosclerosis, doctors today rely on ultrasonic grayscale images to visually assess vascular function and how very large arteries move. The less mobility, the more developed the case of atherosclerosis.

But it is an indirect measurement. Better diagnoses can be made when the stiffness of the blood vessels can be analysed, explains Elira Maksuti, a researcher at the Department of Medical Imaging Technology at KTH.

"You need a doctor who is an expert and has extensive experience in order to get a good diagnosis," she says.

But by combining the technologies of shear wave elastography and ultrasound, Maksuti and researcher Erik Widmanh, have developed an inexpensive and non-invasive method not only for checking the stiffness of blood vessels, but for analysing the type of plaque present in the artery.

Maksuit says their method not only offers a potentially more effective way to diagnose atherosclerosis, but the ultrasound technology that it relies on is less expensive -- and safer -- than other imaging alternatives, such as magnetic resonance imaging (MRI) or computed tomography (CT).

The technique was tested on artificial blood vessels, or "phantom" vessels, which allowed the researchers to experiment with not only vascular stiffness, but also pressure and flow.

Maksuti says that with the success of tests on these phantoms, the next step is testing the technique with blood vessels from pigs. "These tests also look very promising," she says.

"We see two major future applications before us," she says. "The first is to determine when a patient's blood vessels are becoming rigid, that is, when the atherosclerosis process begins.

"The second application is to be able to diagnose the type of calcification -- or plaque -- present in the blood vessel." Not all plaque is the same: it ranges from hard to soft. If the plaque is soft and has a thin, hard shell, it is more likely to come loose inside the blood vessel.

It's a difficult distinction to determine. But the information is critical in deciding whether to open the artery surgically. "Today it is rather a matter of guessing. A doctor cannot know," she says. And to complicate matters, such operations can also generate strokes.

Source: KTH The Royal Institute of Technology

Odor that smells like blood: Single component powerful trigger for large carnivores

African wild dogs compete for a log impregnated with blood or a single component. Both were equally attractive. Credit: Linköping University

People find the smell of blood unpleasant, but for predatory animals it means food. When behavioural researchers at Linköping University in Sweden wanted to find out which substances of blood trigger behavioural reactions, they got some unexpected results.

Matthias Laska is professor of zoology, specialising in the sense of smell. For some time his focus has been on scents that directly affect the behaviour of animals.

"For predators, food scents are particularly attractive, and much of this has to do with blood. We wanted to find out which chemical components create the scent of blood," he says.

The study, conducted at Kolmården Wildlife Park, found that for the animals, one particular component of blood odour was just as engaging as the blood odour itself.

"It's a completely new discovery that raises interesting questions on evolution," says Prof Laska.

The study has been published in the scientific journal PLOS ONE.

When Prof Laska did a search for the contents of volatile substances in mammalian blood, he found nothing. Human blood has been analysed for disease markers, but we have very little information on the substances that give blood its characteristic scent.

A master's student was sent to Friedrich-Alexander-Universität in Erlangen Germany, to analyse mammalian blood with the help of gas chromatography and mass spectrometry, methods used for separating and identifying chemical compounds in a sample. The machine detected some 30 substances, of which some are decomposition products from fats. But the machine lost the job to the human scent experts who had also been engaged. They identified scents that the gas chromatograph missed completely.

One substance stood out: an aldehyde called trans-4,5-epoxy-(E)-2-decenal, which emits the typical metallic scent that humans associate with blood.

Once the researchers had identified a scent candidate that the predators should be attracted to, they wanted to test whether the predators were actually attracted to it in reality. So they designed a study to be conducted at Kolmården Wildlife Park, involving four predator species. How would the four predators -- Asian wild dogs, African wild dogs, South American bush dogs and Siberian tigers -- react when they caught a whiff of the scent?

Half-metre long wooden logs were impregnated with four different liquids: lab-produced aldehyde, horse blood, fruit essence, and a near-odourless solvent. The animals were exposed to one scent per day in their regular enclosure, while a group of students carefully observed their behaviour.

The results were unequivocal. The logs containing aldehyde were just as attractive stimuli as those containing blood, while the two other logs aroused little interest. The commonest behaviours were sniffing, licking, biting, pawing and toying. The tiger was the most persistent, while the South American bush dogs lost interest more quickly than the other species.

The study is the first to show that a single component can be just as attractive as the complex odour.

"How this has developed through evolution is an interesting question. Perhaps there is a common denominator for all mammalian blood," says Prof Laska.

He has plans for several follow-ups of the study, including how prey animals such as mice react to blood odour.

For the wildlife park, the study provided results that can be used in its daily operations. Animals in captivity require stimulation, so as not to deteriorate or become fat. The odourised logs can be a popular addition to the animal's environment.

Source: Linköping University