An official website of the United States government
Thromboembolism – that is, clot formation and the subsequent fragmentation of clot – is a leading cause of death worldwide. Clots’ mechanical properties are critical determinants of both the embolization process and the pathophysiological consequences thereof. Thus, understanding and quantifying the mechanical properties of clots is important to our ability to treat and prevent thromboembolic disease. However, assessing these properties from in vivo clots is experimentally challenging. Therefore, we and others have turned to studying in vitro clot mimics instead. Unfortunately, there are significant discrepancies in the reported properties of these clot mimics, which have been hypothesized to arise from differences in experimental techniques and blood sources. The goal of our current work is therefore to compare the mechanical behavior of clots made from the two most common sources, human and bovine blood, using the same experimental techniques. To this end, we tested clots under pure shear with and without initial cracks, under cyclic loading, and under stress relaxation. Based on these data, we computed and compared stiffness, strength, work-to-rupture, fracture toughness, relaxation time constants, and prestrain. While clots from both sources behaved qualitatively similarly, they differed quantitatively in almost every metric. We also correlated each mechanical metric to measures of blood composition. Thereby, we traced this inter-species variability in clot mechanics back to significant differences in hematocrit, but not platelet count. Thus, our work suggests that the results of past studies that have used bovine blood to make in vitro mimics – without adjusting blood composition – should be interpreted carefully. Future studies about the mechanical properties of blood clots should focus on human blood alone.
more »
« less
Nonlinear, dissipative phenomena in whole blood clot mechanics
When a thrombus breaks off and embolizes it can occlude vital vessels such as those of the heart, lung, or brain. These thromboembolic conditions are responsible for 1 in 4 deaths worldwide. Thrombus resistance to embolization is driven by its intrinsic fracture toughness as well as other, non-surface-creating dissipative mechanisms. In our current work, we identify and quantify these latter mechanisms toward future studies that aim to delineate fracture from other forms of dissipation. To this end, we use an in vitro thrombus mimic system to produce whole blood clots and explore their dissipative mechanics under simple uniaxial extension, cyclic loading, and stress-relaxation. We found that whole blood clots exhibit Mullins-like effect, hysteresis, permanent set, strain-rate dependence, and nonlinear stress-relaxation. Interestingly, we found that performing these tests under dry or submerged conditions did not change our results. However, performing these tests under room temperature or body temperature conditions yielded differences. Importantly, because we use venous blood our work is most closely related to venous in vivo blood clots. Overall, we have demonstrated that whole blood clots show several dissipative phenomena – similarly to hydrogels – that will be critical to our understanding of thrombus embolization.
more »
« less
- PAR ID:
- 10317573
- Date Published:
- Journal Name:
- Soft Matter
- Volume:
- 16
- Issue:
- 43
- ISSN:
- 1744-683X
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
More Like this
-
-
Thrombus formation in blood-contacting medical devices is a major concern in the medical device industry, limiting the clinical efficacy of these devices. Further, a locally formed clot within the device has the potential to detach from the surface, posing a risk of embolization. Clot embolization from blood-contacting cardiovascular devices can result in serious complications like acute ischemic stroke and myocardial infarction. Therefore, clot embolization associated with device-induced thrombosis can be life-threatening and requires an enhanced fundamental understanding of embolization characteristics to come up with advanced intervention strategies. Therefore, this work aims to investigate the adhesive characteristics of blood clots on common biocompatible materials used in various cardiovascular devices. This study focuses on characterizing the adhesion strength of blood clots on materials such as polytetrafluoroethylene (PTFE), polyurethane (PU), polyether ether ketone (PEEK), nitinol, and titanium, frequently used in medical devices. In addition, the effect of incubation time on clot adhesion is explored. Results from this work demonstrated strongest clot adhesion to titanium with 3 h of incubation resulting in 1.06 ± 0.20 kPa detachment stresses. The clot adhesion strength on titanium was 51.5% higher than PEEK, 35.9% higher than PTFE, 63.1% higher than PU, and 35.4% higher than nitinol. Further, adhesion strength increases with incubation time for all materials. The percentage increase in detachment stress over incubation time (ranging from 30 min to 3 h) for polymers ranged from at least 108.75% (PEEK), 140.74% (PU), to 151.61% (PTFE). Whereas, for metallic surfaces, the percentage rise ranged from 70.21% (nitinol) to 89.28% (titanium). Confocal fluorescence imaging of clot remnants on the material surfaces revealed a well-bounded platelet-fibrin network at the residual region, representing a comparatively higher adhesive region than the non-residual zone of the surface.more » « less
-
Abstract Despite recent advances in the development of computational methods of modeling thrombosis, relatively little effort has been made in developing methods of modeling blood clot embolization. Such a model would provide substantially greater understanding of the mechanics of embolization, as in-vitro and in-vivo characterization of embolization is difficult. Here, a method of computationally simulating embolization is developed. Experiments are performed of blood clots formed in a polycarbonate tube, where phosphate-buffered saline is run through the tube at increasing flow rates until the clot embolizes. The experiments revealed embolization can be initiated by leading edge and trailing edge detachment or by non-uniform detachment. Stress-relaxation experiments are also performed to establish values of constitutive parameters for subsequent simulations. The embolization in the tube is reproduced in silico using a multiphase volume-of-fluid approach, where the clot is modeled as viscoelastic. By varying the constitutive parameters at the wall, embolization can be reproduced in-silico at varying flow rates, and a range of constitutive parameters fitting the experiments is reported. Here, the leading edge embolization is simulated at flow rates consistent with the experiments demonstrating excellent agreement in this specific behavior.more » « less
-
Endovascular sonothrombolysis has gained significant attention due to its benefits, including direct targeting of the thrombus with sonication and reduced side effects. However, the small aperture of endovascular transducers restricts the improvement of their potential clinical efficiency due to inefficient acoustic radiation. Hence, in an earlier study, we used vortex ultrasound with an endovascular ultrasound transducer to induce shear stress and enhance the clot lysis. In this study, the vortex acoustic transduction mechanism was investigated using numerical simulations and hydrophone tests. Following this characterization, we demonstrated the performance of the vortex ultrasound transducer in thrombolysis of retracted clots in in vitro tests. The test results indicated that the maximum lysis rates were 79.0% and 32.2% with the vortex ultrasound for unretracted and retracted clots, respectively. The vortex ultrasound enhanced the efficiency of the thrombolysis by approximately 49%, both for retracted and unretracted clots, compared with the typical non-vortex ultrasound technique. Therefore, the use of endovascular vortex ultrasound holds promise as a potential clinical option for the thrombolysis of retracted clots.more » « less
-
Abstract Studying and quantifying the mechanics of blood clots is essential to better diagnosis and prognosis of, as well as therapy for, thromboembolic pathologies such as strokes, heart attacks, and pulmonary embolisms. Unfortunately, mechanically testing blood clots is complicated by their softness and fragility, thus making the use of classic mounting techniques, such as clamping, challenging. This is particularly true for mechanical testing under large deformation. Here, we describe protocols for creating in vitro blood clots and securely mounting these samples on mechanical test equipment. To this end, we line 3D‐printed molds with a hook‐and‐loop fabric that, after coagulation, provides a secure interface between the sample and device mount. In summary, our molding and mounting protocols are ideal for performing large‐deformation mechanical testing, with samples that can withstand substantial deformation without delaminating from the apparatus. © 2021 Wiley Periodicals LLC. Basic Protocol 1: Cube‐shaped blood clot preparation Basic Protocol 2: Sheet‐shaped blood clot preparationmore » « less
- Free Publicly Accessible Full Text
-
Accepted Manuscript1.0
- Journal Article:
- https://doi.org/10.1039/D0SM01317J
