Abstract 511: Novel Thrombolytic Agent Showing Unique Lysis Of Platelet-Rich Thrombi

Background: Acute arterial thrombosis, formed primarily by platelets and vWF under high shear, causes significant morbidity and mortality by occluding end-organ blood flow. These platelet thrombi are often resistant to thrombolysis by tPA and other therapeutics due to minimal fibrin. We have recently discovered a new compound N,N'-diacetyl-L-cystine (DiNAC) that effectively lyses platelet-rich blood clots. Objective: The purpose of this study is to evaluate the efficacy of DiNAC as a lytic agent against platelet-rich occlusive thrombi made from human whole blood. Methods: Occlusive thrombi were made from heparinized human whole blood, collected from healthy volunteers, in an in-vitro flow loop. Blood was perfused using a syringe pump through a glass stenosis coated with fibrillar collagen and observed through a microscope with continuous recording. Pressure was measured continuously upstream and downstream of the stenosis. After thrombosis occurred, a 10mM DiNAC solution was perfused. Lysis was measured using image capture and pressure differential recording. Thrombolytic response of DiNAC was compared with saline control and analyzed for significance. Results: Perfusion with 10 mM DiNAC created effective thrombolysis of the clot with visual flow restoration. The pre-stenosis backpressure returned to pre-occlusion levels and thrombus surface area was reduced by 70% (n=10). In contrast, saline control had no appreciable effect on surface area or pressure (n=10, p<0.01). Conclusion: DiNAC is a novel compound with the ability to lyse platelet-rich arterial thrombi, repeatably restoring flow after occlusive platelet thrombus formation in-vitro with human blood. These promising results pave the way for clinical studies evaluating the effectiveness and safety of DiNAC for arterial thrombolysis.