期刊
CURRENT OPINION IN HEMATOLOGY
卷 25, 期 5, 页码 382-388出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/MOH.0000000000000452
关键词
anticoagulation; aptamer; cardiopulmonary bypass; contact pathway; hemostasis
类别
资金
- NIH [HL-065222, F30 HL-127977, T32 GM-007171]
Purpose of reviewSince the selection of the first thrombin-binding aptamer in 1992, the use of nucleic acid aptamers to target specific coagulation factors has emerged as a valuable approach for generating novel anticoagulant and procoagulant therapeutics. Herein, we highlight the most recent discoveries involving application of aptamers for those purposes.Recent findingsLearning from the successes and pitfalls of the FIXa-targeting aptamer pegnivacogin in preclinical and clinical studies, the latest efforts to develop antidote-controllable anticoagulation strategies for cardiopulmonary bypass that avoid unfractionated heparin involve potentiation of the exosite-binding factor X (FX)a aptamer 11F7t by combination with either a small molecule FXa catalytic site inhibitor or a thrombin aptamer. Recent work has also focused on identifying aptamer inhibitors of contact pathway factors such as FXIa and kallikrein, which may prove to be well tolerated and effective antithrombotic agents in certain clinical settings. Finally, new approaches to develop procoagulant aptamers to control bleeding associated with hemophilia and other coagulopathies involve targeting activated protein C and tissue plasminogen activator.SummaryOverall, these recent findings exemplify the versatility of aptamers to modulate a variety of procoagulant and anticoagulant factors, along with their capacity to be used complementarily with other aptamers or drugs for wide-ranging applications.
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