Thirdhand smoke (THS), the persistent residue of tobacco smoke that remains after a cigarette is extinguished, materialized as a threat for human health over the last decade. There is growing body of evidence documenting THS-induced health risks, including cardiovascular disease (CVD). Nonetheless, there remains skepticism regarding THS existence, and much less is known or has been investigated with regard to its toxicity. The goal of my research studies is to investigate the mechanistic impact of THS exposure and its toxicants in the context of platelet function, and whether sex plays any role in these effects. Two specific aims are proposed: Specific Aim 1. Investigate the impact of THS-exposure on platelet-dependent disease states. This aim will investigate the consequences of exposure to THS on platelet dependent disease states. In light of the fact that hyperactive platelets result in a prothrombotic state, subsequent studies will, similarly, examine whether THS participates in the development of thrombotic disorders. Finally, given that the coagulation system may contribute to the THS phenotype, its effects on plasma levels of thrombosis markers (e.g., thrombin), TAT and other elements will also be examined. These studies will be conducted in a dose-, time-, and gender-dependent fashion, given the importance of these issues for understanding the THS effects. Specific Aim 2. Investigate the mechanism by which THS-exposure modulates platelet function. This aim will investigate the ability of THS exposure to enhance platelet function, spreading, calcium homeostasis, biochemical markers of platelet activation, isoprostanes levels, and whether effects are receptor mediated. We will also determine the major route of THS exposure, all of which in a dose, time and sex dependent manner.