The search for new antithrombotic mechanisms and therapies that may spare hemostasis

Edward F. Plow, Yunmei Wang and Daniel I. Simon


Current antithrombotic drugs, including widely used antiplatelet agents and anticoagulants, are associated with significant bleeding risk, which increases morbidity and mortality. Nevertheless, there is emerging experimental evidence that suggests that the molecular and cellular mechanisms of hemostasis and thrombosis can be separated, thereby raising the possibility of new antithrombotic therapeutic targets with reduced bleeding risk. We summarize some recently emerging examples of agents with antithrombotic activities that seem to spare hemostasis. Specific activities within each of the two major pathways leading to thrombus formation, from within the platelet and the coagulation system, give credence to the notion that physiologic hemostasis and pathologic thrombosis are mechanistically distinct and can be selectively inhibited. Targeting these differences may be the forerunning of a new generation of antithrombotic therapy. Among the less widely appreciated targets, we highlight the interaction between integrin αMβ2 (Mac-1, CD11b/CD18) on leukocytes and GPIbα on platelets that appears to distinguish thrombosis from hemostasis. This specific receptor: counter-receptor pairing not only emphasizes the role of leukocytes in thrombosis, but also identifies a novel interaction that could be targeted and might ultimately lead to a safer antithrombotic strategy.

  • Submitted October 11, 2017.
  • Accepted February 13, 2018.