期刊
BLOOD REVIEWS
卷 32, 期 6, 页码 433-448出版社
CHURCHILL LIVINGSTONE
DOI: 10.1016/j.blre.2018.04.001
关键词
Factor XI; Factor XII; Prekallikrein; Thrombosis; Contact activation
类别
资金
- National Institutes of Health [HL81326, HL58837, HL140025, HL101972, GM116184, AI088937]
- NATIONAL HEART, LUNG, AND BLOOD INSTITUTE [R35HL140025, R01HL058837, R01HL101972, R01HL081326] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES [R43AI088937, R44AI088937] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES [R01GM116184] Funding Source: NIH RePORTER
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.
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