Impairment of vascular integrity is a hallmark of inflammatory diseases. In inflammatory bleeding, leukocyte diapedesis causes endothelial leakage with spillover of red blood cells and plasma contents. Previous work has emphasized the crucial role of neutrophils in causing endothelial microdefects, which are subsequently sealed by single platelets. We have recently provided evidence that platelet migration and haptotaxis are essential for platelet-mediated vascular homeostasis in inflammation and the prevention of both inflammatory bleeding and microbial dissemination. However, it is unclear how platelets – falling short of neutrophil size – exert this function locally. Here, we show that single procoagulant platelets are induced by inflammation in-vivo. Using a novel lactadherin-based compound to identify procoagulant activation (PA), we detect phosphatidylserine (PS)-positive single platelets in the inflamed vasculature that form fibrin(ogen)-positive microthrombi adherent to the endothelium. Prevention of this microthrombus formation by anticoagulation aggravates inflammatory bleeding in-vivo. In-vitro, we show that migrating platelets become procoagulant when sensing collagen fibers in a process mediated by GPIIBIIIA and GPVI signaling and the PA factors Cyclophilin D (CypD) or TMEM16F. In line, platelet-specific genetic loss of either CypD or TMEM16F, both of which are crucial for platelet PA, aggravates inflammatory bleeding. In-vitro, platelet CypD deficiency desensitizes migrating platelets to PA and prolongs the time to supramaximal calcium plateaus. Finally, targeting of platelet PA by combined pharmacological blockade of GPVI and GPIIBIIIA reduces circulating procoagulant platelets in-vivo and exacerbates alveolar hemorrhage. Our findings provide evidence for an essential role of procoagulant platelets in the prevention of inflammatory bleeding.