Specific and common mechanisms of hypercoagulability and thromboinflammation in MPN and COVID-19. Mechanisms of hypercoagulability in MPN and COVID-19 share common pathways. Major differences among the 2 diseases rely on the type of trigger of clotting activation, which in COVID-19 is due to the action of acute infection by SARS-CoV-2 on the prothrombotic characteristics of various hemostatic compartments. A maladaptive hyperactivation of innate immune systems in COVID-19 is also responsible for the activation of the complement cascade and endothelial dysfunction. Differently, in MPN, the systemic hypercoagulability results from the exposure to a long-term (chronic) subinflammatory condition, caused by the abnormal and clonal proliferation of JAK2-mutated myeloid cells.