Biomechanical profiling of in vitro blood clots: sensitivity to sex, age, and blood composition in a healthy adult population.

Abstract

Blood clots' mechanical properties are important in both their physiological role and in the initiation and progression of thromboembolic diseases. Because studying blood clot properties in vivo is difficult, many prior studies have investigated the properties of in vitro clots instead. However, much remains to be understood about in vitro clots, especially those derived from human blood. For example, the association between subject-specific factors and clot mechanical properties is currently unknown. Our objective is to fill this knowledge gap and study the sensitivity of in vitro blood clots to subject-specific factors, including sex, age, and blood composition. We drew blood from healthy adults aged 19-46, coagulated clots into mechanical test specimens, and characterized their properties. Specifically, we quantified clot stiffness, fracture toughness, contractility, and hysteresis. We then quantified the relative dependence of those properties on subject-specific factors, including sex, age, and blood composition. We found that there is significant variation in clot properties within healthy subjects. Clots from female subjects' blood are stiffer, more resistant to fracture, and show more hysteresis compared to clots from male subjects. However, we found no association between clot properties and age and only a weak association with clot composition, e.g., hematocrit. Finally, even together, sex, age, and blood composition only moderately explain the observed variability in clot mechanical properties. Our work therefore suggests that in vitro clots may capture relevant information not reflected in standard clinical data. Future studies should investigate in vitro clots' potential as biomarkers for thrombotic risk and treatment response.