General mechanisms of coagulation and targets of anticoagulants (Section I) Academic Article uri icon

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abstract

  • SummaryContrary to previous models based on plasma, coagulation processes are currently believed to be mostly cell surface-based, including three overlapping phases: initiation, when tissue factor-expressing cells and microparticles are exposed to plasma; amplification, whereby small amounts of thrombin induce platelet activation and aggregation, and promote activation of factors (F)V, FVIII and FXI on platelet surfaces; and propagation, in which the Xase (tenase) and prothrombinase complexes are formed, producing a burst of thrombin and the cleavage of fibrinogen to fibrin. Thrombin exerts a number of additional biological actions, including platelet activation, amplification and self-inhibition of coagulation, clot stabilisation and anti-fibrinolysis, in processes occurring in the proximity of vessel injury, tightly regulated by a series of inhibitory mechanisms. ″Classical″ anticoagulants, including heparin and vitamin K antagonists, typically target multiple coagulation steps. A number of new anticoagulants, already developed or under development, target specific steps in the process, inhibiting a single coagulation factor or mimicking natural coagulation inhibitors.

authors

  • Husted, Steen
  • Wallentin, Lars
  • Andreotti, Felicita
  • Arnesen, Harald
  • Bachmann, Fedor
  • Baigent, Colin
  • Huber, Kurt
  • Jespersen, Jørgen
  • Kristensen, Steen
  • Lip, Gregory YH
  • Morais, João
  • Rasmussen, Lars
  • Siegbahn, Agneta
  • Verheugt, Freek WA
  • Weitz, Jeffrey
  • De Caterina, Raffaele

publication date

  • 2013