With World Thrombosis Day just passed, we would like to look back over five publications, using #CellixTech, that have forwarded the world's knowledge of thrombosis. Thrombosis is often an integral part of the pathology of the world's most deadly cardiovascular diseases. This makes it currently responsible for one in four deaths around the world.
Cellix has had a close relationship with thrombosis research for a long time now as our microfluidic pumps and biochips have proven to be exceptionally useful in modelling blood flow in the body. The Vena8 Fluoro+, in particular, has allowed the scientific community to take great strides towards understanding the cardiovascular system in health and disease.
Although thrombosis is still a significant burden on the world, research in the field has changed our perspective on the conditions it causes. We now see the formation of thrombosis (and the diseases it causes) as largely preventable. To raise awareness of the brilliant work being done on thrombosis research we are going to take a look at some of the best publications using Cellix technology to come out within the last year.
Researchers believe it may be possible to look at a person's individual ability to break down clots as a factor in predicting their risk of cardiovascular disease.
Impaired Spontaneous/Endogenous Fibrinolytic Status as New Cardiovascular Risk Factor?
One of our favorite publications to ever come out using Cellix tech was “Microfluidic Modeling of Thrombolysis” by Stéphane Loyau et. al in 2018. Here they used the Vena8 Fluoro+ chip to grow a platelet/fibrin-rich thrombus — also known as a blood clot — before passing specific drugs down the microfluidic channel to see how they affected the clot. The main aim was to look at the effects of drugs that broke apart the fibrin part of the clot. Hoping to see if the breakdown affected the platelet parts as well. Surprisingly, it turned out that the platelet parts continued to grow even when the fibrin parts were broken down.
More recently though, this research was then incorporated into a review of the body’s own ability to break down the fibrin part of blood clots — endogenous fibrinolysis. By using Cellix tech to understand the mechanisms involved in breaking down clots, it is now possible to assess whether these mechanisms are working correctly in patients dealing with thrombosis. The review found that impairments in a person's endogenous fibrinolysis system could be a prevalent risk factor in acute coronary syndrome. It’s exciting research as it can inform people of possible risks of cardiovascular problems in their future. With this information, proactive steps can be taken and lives will be saved.
Graphic from the review above - Gorog DA, Lip GYH.
Scientists have discovered a novel coating that can lower the chances of infection from medical devices.
A Novel Medical Device Coating Prevents Staphylococcus aureus Biofilm Formation on Medical Device Surfaces
In this paper, the researchers were able to discover drugs that could prevent the possibility of infection from the use of medical devices such as intravascular catheters — one of the most important devices in treating cardiovascular pathology.
Here again, the Vena8 Fluoro+ chip was used to simulate blood flow through a channel and then the bacterium Staphylococcus aureus was added to see if it took hold and caused an infection. After adding the pathogen, researchers could see the growth of a bacterial layer on the cells seeded within the chip (S. aureus is the most common bacterium associated with medical device infections).
The theory was that these bacteria needed small clots or thrombi to attach to. So they added thrombin inhibitors to the Vena8 chip to see if it stopped the infection. It was exciting to see that these inhibitors had a significant impact on the chances of S.aureus attaching to the cells within the chip.
This research indicates that thrombin inhibitors can be used during procedures involving medical devices to lower the chances of an infection. With the use of medical devices becoming more common now in medicine, this information will have a significant impact on the number of infections people receive which is currently a known and very dangerous complication.
A specific bacteria has been found able to reduce the chances of an allergic reaction to anti-clotting medication.
Cleavage of anti-PF4/Heparin IgG by a Bacterial Protease and Potential Benefit in Heparin-Induced Thrombocytopenia
One of the biggest problems dealing with thrombosis is the possibility of heparin-induced thrombocytopenia (HIT). Heparin is used in patients with a high risk of forming a blood clot such as in acute coronary syndrome. But it has been discovered that some patients develop an allergic response to the drug which can actually result in a significant increase in clotting instead of a reduction.
This group used the Vena8 Fluoro+ to simulate the immunocomplex that forms during an allergic reaction to heparin and discovered that the addition of the bacterial protease (an enzyme produced by bacteria to break antibodies) from Streptococcus pyogenes can hinder the body's immune response and stop the occurrence of HIT.
Although the most severe symptoms of HIT only occur in a small population, it has been discovered that quite a significant number of people have an allergic response (up to 40%). So it is evidently important to be looking into HIT to maintain control over and hopefully lower the number of complications.
A blood clot under scanning electron microscopy.
Researchers have created 'microbubbles' that can find clots and allow them to be viewed easier under ultrasound.
Functionalized Polymer Microbubbles as New Molecular Ultrasound Contrast Agent to Target P-selectin in Thrombus
In this study, researchers looked at combining polymer microbubbles with a novel compound that binds activated platelet cells. It is known that these microbubbles can be seen with ultrasound and so the idea here was to create a system that can visualise the activated platelets in thrombi and provide a diagnosis. Current diagnosis often involves venography (injecting a radioactive dye through the foot and then having an X-ray) but this is a very invasive method that can impair the patient.
The researchers took fucoidan, a molecule known to attach to activated platelet cells, and added it to their polymer microbubble. They then tested the fucoidan-microbubble’s ability to bind the activated platelets under flow conditions in the Vena8 Fluoro+ chips.
It turns out that the new fucoidan-microbubbles are very good at finding clumps of activated platelets and the researchers were able to view them with ultrasound imaging. This has significant scope as ultrasound imaging is one of the least invasive forms of viewing the body and it could lead to improved comfort and decreased stress in patients receiving a diagnosis of thrombosis.
Scientists have discovered a specific protein presentation that could predict the chances of a bleeding complication from thrombosis treatment.
Platelet CD40 Ligand and Bleeding During P2Y12 Inhibitor Treatment in Acute Coronary Syndrome
One of the biggest complications in treating thrombosis or other coronary syndromes is the possibility of increased or uncontrolled bleeding. Thrombi are the result of over-activation and aggregation of platelets but this system is still required for normal blood clotting. Without it, blood may flow freely out of the cardiovascular system with no way of stopping itself.
This team used the Vena8 Fluoro+ chip to simulate blood flow in the body and assess the relationship between a P2Y12 antiplatelet therapy and the expression of specific cell receptors. They found that levels of the receptor CD40L presented on platelets were significantly associated with the chance of a bleeding occurrence, whereas levels of CD40L being released by platelets were not associated with bleeding.
This information can be used as a new way of assessing bleeding risk in patients being treated with P2Y12 antiplatelet therapy. A tool that could save many lives in the future.
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