Plasma contact factors as therapeutic targets

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

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

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)
JournalBlood Reviews
DOIs
StateAccepted/In press - Jan 1 2018

Fingerprint

Hemostasis
Hemorrhage
Anticoagulants
Thrombosis
Factor XI
Prekallikrein
Factor Xa
Fibrinolytic Agents
Partial Thromboplastin Time
Blood Coagulation
Warfarin
Drug Delivery Systems
Protease Inhibitors
Thrombin
Biochemistry
Therapeutics
Population
Proteins

Keywords

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

ASJC Scopus subject areas

  • Hematology
  • Oncology

Cite this

Plasma contact factors as therapeutic targets. / Tillman, Benjamin F.; Gruber, Andras; McCarty, Owen; Gailani, David.

In: Blood Reviews, 01.01.2018.

Research output: Contribution to journalArticle

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