Targeting PAR1 is another potential attractive approach that could counter the negative effects of both thrombin formation and activation of pro-inflammatory pathways by the coagulation system. Although PAR1 antagonists are unlikely to impact on VTE they could have beneficial effects in COVID-19 pneumonia through several potential mechanisms: 1) direct anti-platelet effect potentially reducing the incidence of coronary and cerebral artery thrombosis [103]; 2) inhibition of inflammatory signalling pathways downstream of thrombin resulting in attenuated inflammatory responses and inflammatory cell recruitment; 3) protection from the development of post-ARDS pulmonary fibrosis [104]; 4) maintaining integrity of the endothelial alveolar barrier, reducing pulmonary oedema; and 5) indirectly attenuating coagulation activation by reducing inflammation. Several PAR1 antagonists are in development but only one has been clinically approved, vorapaxar (Zontivity). Vorapaxar is a highly selective small molecule PAR1 antagonist but its long half-life (20 h) and inhibitory effects on platelets (24–48 h) [105, 106] call for cautious use in critically ill patients, particularly because a reversal agent does not exist. Trials in the secondary prevention of acute coronary syndromes have shown that there is also potential for bleeding, although in these trials patients were on dual anti-platelet medication. PAR1 antagonism could therefore represent a potential approach to halt progression of the disease in hospitalised patients at risk of critical illness. Future research and carefully designed trials in this area would be welcomed. Table 1 provides a summary of the effects of therapeutics targeting coagulation proteinases in pneumonia, lung injury and sepsis in preclinical and clinical studies.