New research from Emory University may revolutionize how stroke, heart attack, related blood-clotting conditions are treated

Blood clots are associated with life-threatening conditions such as sepsis, sickle cell disease, heart attack and stroke. However, new research from Emory University may revolutionize how clinicians understand and treat these harmful blood clots, or thrombi, a byproduct of a condition called thromboinflammation. In a groundbreaking study published in Nature, researchers have discovered the potential to provide life-saving medications to patients with blood clots at the right time, with the right dose, in novel combinations based on a new model.

To gain these insights, researchers developed a thromboinflammation-on-a-chip model that can sustain the clots for several months in a more accurate, human-like manner, leveraging 3D microvessels on a chip. This novel model allows the thrombi to exist in human blood and veins for months and resolve as they would naturally in a real patient. Researchers are then able to track the blood clot and measure the effectiveness of various treatment options. This model differs from existing models, which can only sustain blood clots for short periods. Additionally, this new model includes the real cells necessary for clot resolution, whereas other lab models do not.

Wilbur Lam, corresponding author of the study, professor at Emory University and Georgia Tech, and a clinician at Children’s Healthcare of Atlanta, explains that little is known about how blood clots are resolved in real life after one survives a stroke or heart attack, but replicating the process on a chip can reveal critical information in the application or development of new treatments.

“Because we created this system where we observe a blood clot on a chip over long periods of time, such as days to weeks, we can map out its entire resolution process, and that has never been done before,” says Lam, MD, PhD. “This is significant because animal models are challenging. While extremely difficult to closely observe a clot in a specific part of a mouse for weeks, we can now do it on a chip and are able to monitor it closely.”

Yongzhi Qiu, a corresponding author on the study, also emphasized the importance of the model’s life-like accuracy. “Our practical measure is so unique because it is hard to study thrombi in clinical settings due to the low spatial resolution of existing tools, so it’s harder to clearly see how these clots resolve,” says Qiu, PhD, and assistant professor in the Department of Pediatrics at Emory University School of Medicine. 

For this study, Qiu also developed the hydrogel for this model using human blood in a human vein, making it the only model to integrate 3D microvessels that can be stressed and monitored under physiologically relevant conditions.

Charting the future of blood clotting treatment

In addition to stroke or cardiac arrest, it’s noteworthy that hypertension, diabetes, severe trauma, burns and other infections are also factors in developing thromboinflammation, leaving much of the nation at risk.

Since this model opens the door to understanding how blood clots naturally resolve, researchers can now further study the timing, dosage, and impact of existing medical interventions, as well as possible new combinations. One such discovery from this study is the vital role of neutrophils, which both resolve thrombi and create inflammation — a double-edged sword, according to Lam.

Additionally, this study reveals that the treatment used after a stroke, tPA, or Tissue Plasminogen Activator, also directly repairs any vasculature, which was previously unknown.

The study also suggests that combining existing mediations may protect the endothelial function, or the opening and closing of arteries, in patients with sickle cell disease. Finally, this study notes that those experiencing bone marrow transplantation may benefit from certain drug combinations to protect against veno-occlusive disease, a condition resulting from high doses of chemotherapy that can cause liver damage by blocking small veins in the liver.

“One of the biggest things about being able to create thrombi under inflammatory conditions is that we are now able to map it out over time and develop hypotheses about which drugs would be most helpful, in which context, and importantly, when,” says Lam, making the study the cornerstone of future research and clinical trials in the quest to save lives.