Plasma contact factors as therapeutic targets

Benjamin F. Tillman, Andras Gruber, Owen J.T. McCarty, David Gailani

Research output: Contribution to journalReview articlepeer-review

49 Scopus citations


Direct oral anticoagulants (DOACs) are small molecule inhibitors of the coagulation proteases thrombin and factor Xa that demonstrate comparable efficacy to warfarin for several common indications, while causing less serious bleeding. However, because their targets are required for the normal host-response to bleeding (hemostasis), DOACs are associated with therapy-induced bleeding that limits their use in certain patient populations and clinical situations. The plasma contact factors (factor XII, factor XI, and prekallikrein) initiate blood coagulation in the activated partial thromboplastin time assay. While serving limited roles in hemostasis, pre-clinical and epidemiologic data indicate that these proteins contribute to pathologic coagulation. It is anticipated that drugs targeting the contact factors will reduce risk of thrombosis with minimal impact on hemostasis. Here, we discuss the biochemistry of contact activation, the contributions of contact factors in thrombosis, and novel antithrombotic agents targeting contact factors that are undergoing pre-clinical and early clinical testing.

Original languageEnglish (US)
Pages (from-to)433-448
Number of pages16
JournalBlood Reviews
Issue number6
StatePublished - Nov 2018


  • Contact activation
  • Factor XI
  • Factor XII
  • Prekallikrein
  • Thrombosis

ASJC Scopus subject areas

  • Hematology
  • Oncology


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