The activation of tissue factor by high intensity focused ultrasound - A pathway to acoustic-biochemical hemostasis

High intensity focused ultrasound (HIFU) is believed to have great potential for inducing hemostasis in severely bleeding trauma victims. The addition of HIFU-activated biomolecular substances to the blood during treatment could significantly reduce the time required to achieve hemostasis, but such substances must remain inactive everywhere except at the site of injury. The integral-membrane protein, tissue factor (TF), is by far the most potent known trigger for the blood clotting cascade. We propose to employ liposomes with the extracellular domain of TF facing the lumen ("encrypted TF") to allow the TF molecules to be introduced into the blood stream without causing systemic activation of coagulation. HIFU sonication at the site of injury will be used to break up the liposomes and thereby expose TF to the plasma, thus combining the hemostatic potential of HIFU along with an increase in the rate of clot formation triggered by TF. In our initial studies we have produced a range of concentrations of liposomes containing encrypted TF in a buffer solution and exposed them to ultrasound at a number of different intensity levels and duty cycles. Clotting assays were performed to determine the level of the desired effect of the ultrasound. The results suggest that HIFU can be effective in exposing active TF from the encrypted liposomes to accelerate blood clotting at the site of exposure.