Kinetics and mechanics of blood clot contraction

Valerie J. Tutwiler

doi:10.17918/etd-7792

Thrombotic conditions such as heart attacks and strokes are leading causes of death and disability worldwide. Clot contraction, which is the volume shrinkage of the blood clot, has been implicated to play a role in hemostasis, wound healing, and the restoration of blood flow past otherwise obstructive thrombi. Despite these clinical implications, clot contraction is the least studied area of the coagulation process, which can be largely attributed to a previous lack of methodology. To address this need, we developed a novel optical tracking system that allows for the quantitative assessment of clot contraction. These studies revealed that clot contraction is a three-phase process that can be differently affected by platelets, fibrin, and erythrocytes. Platelet count and function have the ability to enhance the extent of clot contraction while increased erythrocytes and fibrin dampen the extent of clot contraction. We developed a three-element active poroviscoelastic model to improve the understanding of how composition of the clot, particularly the presence of erythrocytes, affects the process of clot contraction. We determined that erythrocytes influence clot contraction through both a tensile and compressive resistance, which resulted in a decrease in the extent of contraction coupled with an apparently paradoxical increase in generation of contractile force. The knowledge that blood composition can influence clot contraction coupled with the clinical importance of thrombotic conditions such as stroke and heart attack revealed a need for studies of clot contraction in patients with (pro)-thrombotic conditions. We examined clot contraction in the blood of patients with ischemic stroke, sickle cell disease, and deep vein thrombosis. Interestingly, in all three pathologies we have observed a significant reduction in the extent of clot contraction. With respect to ischemic stroke and deep vein thrombosis, this reduction in clot contraction correlates with a lower platelet count and platelet dysfunction. Whereas, the reduction in contraction in sickle cell disease patients can be attributed to their increased erythrocyte rigidity. Ultimately after a clot is formed it needs to be resolved, which occurs through the enzymatic process of fibrinolysis. Here we examined influence of clot contraction on rate of physiologic or internal fibrinolysis and clinical thrombolysis or external fibrinolysis. Interestingly, clot contraction enhanced the rate of internal fibrinolysis while decreasing the rate of external fibrinolysis. Collectively, these findings provide new information about basic mechanisms of clot contraction and point to its importance with respect to thrombotic conditions, and have the potential to lead to the development of diagnostic assays or therapeutic targets.

Kinetics and mechanics of blood clot contraction

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Kinetics and mechanics of blood clot contraction

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