Uncovering Thrombosis Mechanisms Through Simulated Mosquito Bite Injury Study
Researchers of the Computational Science Lab are making strides in understanding the complexities of thrombosis, a condition that poses a significant risk of heart attacks and strokes. Their approach involves simulating a small injury (mosquito puncture) to learn how the healing mechanism can mistrigger, leading to life-threatening thrombotic diseases.
Thrombosis, the pathological formation of blood clots within blood vessels, is a medical condition that remains a subject of high clinical significance. While blood thinners have been effective in reducing the risk of thrombosis-related complications, they come with substantial side effects.
Christian Spieker, Gábor Závodszky, and Alfons Hoekstra of the Computational Science Lab (CSL), are investigating the mechanisms underlying hemostasis and thrombosis to identify new targets for the next generation of side-effect free antithrombotic therapies.
Understanding the Crucial Difference
The body’s physiological mechanism, hemostasis, involves triggering the blood clotting process in response to bleeding injuries. In contrast to this, thrombosis occurs when the clotting process is mistakenly activated without any external injury, leading to the formation of a clot called a thrombus. These thrombi can narrow blood vessel diameters or completely block them, resulting in life-threatening conditions like heart attacks and strokes. Distinguishing between the healthy and pathologic triggering of hemostatic processes is vital for the development of targeted therapies.
To address this challenge, the group focuses on understanding the fundamental differences between hemostasis and thrombosis by employing sophisticated simulation techniques to replicate the early stages of clot formation in case of a small injury, a mosquito bite.
A Combination of Simulation and Experiment
The researchers employed a cell-resolved blood flow model (HemoCell), developed within their lab, to mimic the initial stages of blood clot formation. Their approach replicated the flow within a vessel that had been punctured by an injury roughly the size of a mosquito bite. Complementary microfluidic experiments were conducted, with precise control of blood flow and pressure, allowing for direct observation of the clotting. The experiments in this work reveal that a necessary step of the clotting process—the aggregation of platelets—is strongly influenced by the local flow environment. This exact flow environment cannot be measured with the currently available technology, however, it can be extracted from the simulations.
Towards Safer Blood Thinners
From the work it is concluded that characteristic flow conditions appear at the site of an injury, that are linked to cellular properties of the blood and enable clot formation. These flow conditions appearing inside a vessel without an injury seem to be a fundamental trigger for thrombosis. Therefore, they might serve as targets for future mechano-selective therapies.