New Technology Enables Early Monitoring and Therapy for tPA-Resistant Blood Clots

Current Methods Offer Limited Effectiveness

The most commonly used thrombolytic treatment today involves the administration of intravenous thrombolytics—most often alteplase or tenecteplase. Both substances are tissue plasminogen activators (tPA) and lead to the breakdown of the fibrin clot by converting plasminogen into plasmin.

However, intravenous thrombolysis also has numerous disadvantages. It can only be applied within a narrow time window (usually up to 4.5 hours from the formation of the clot), has numerous contraindicating factors, or risks intracerebral and systemic bleeding. A significant drawback, however, is the relatively common resistance of clots to tPA thrombolytics, which increases with the size of the vessels. In medium-sized vessels, successful recanalization is achieved in about 42% of cases, while in large vessels, its success rate is less than 30%.

For occlusions of large arteries and tPA-resistant clots, invasive endovascular thrombectomy is therefore used. Although it provides a longer time window and can be combined with other procedures, it primarily depends on the physician's experience and the hospital's equipment. Here, too, a number of complications and contraindications may occur.

What Causes Clot Resistance?

The research team led by Dr. Wen Zeng from Chongqing University focused on tPA-resistant clots and attempted to design a more effective solution. Initially, the scientists investigated the principle causing the resistance of blood clots. Based on several experiments and previous studies, they found that the insolubility of clots is due to neutrophil extracellular traps (NETs) combined with isopeptide bonds and fibrin aggregates.

Based on these findings, they then designed an integrated theranostic platform that operates on the principle of ultrasound, which is currently also used as one of the main imaging methods in diagnosing vascular thrombosis.

The principle by which the new device can dissolve a blood clot is based on the thermal effect of ultrasound waves, which can disrupt the internal structure of the clot. In vitro experiments on mouse models subsequently confirmed that the use of ultrasound significantly reduced the amount of NETs and isopeptide bonds, leading to successful recanalization in more than 90% of cases.

Diagnostic and Therapeutic Simultaneously

In addition to therapy, the new platform will enable the combination of several medical procedures. Thus, it could find application both in diagnostics and in dissolving the clot through sonodynamic mechanical thrombolysis. The entire process will also be able to be flexibly monitored and adjusted in real-time thanks to ultrasound imaging.

However, the scientists admit that the effectiveness of the new method is currently significantly limited, and its enhancement will require a combination of more powerful methods and technologies. For example, deep vein thromboses, which are protected by the solid structure of surrounding tissues and bones, make the non-invasive ultrasound approach challenging. Therefore, further research and optimization of the ultrasound beam propagation will be important.

Editorial Team, Medscope.pro

Source:

Lin L., Ba Z., Tian H. et al. Ultrasound-responsive theranostic platform for the timely monitoring and efficient thrombolysis in thrombi of tPA resistance. Nat Commun 2024; 15 (1): 6610, doi: 10.1038/s41467-024-50741-y.