期刊
THROMBOSIS AND HAEMOSTASIS
卷 109, 期 4, 页码 569-579出版社
GEORG THIEME VERLAG KG
DOI: 10.1160/TH12-10-0772
关键词
Anticoagulants; coagulation; tissue factor; heart disease; coronary heart disease; heart failure; atrial fibrillation
资金
- AstraZeneca
- Bayer
- Boehringer-Ingelheim
- Bristol-Myers Squibb
- Daiichi Sankyo
- Lilly
- Boehringer Ingelheim
- Sanofi-Aventis
- Pfizer
- Athera
- Behring
- Evolva
- Portola
- Roche Diagnostics
- GlaxoSmithKline
- Merck
- Schering-Plough
- Daiichi-Sankyo
- Eli Lilly
- Medicines Company
- Astellas
- Biotronik
- Jaba Recordati
- MSD
- Lilly Portugal
- Johnson Johnson
- Janssen Pharmaceuticals
- MRC [MC_U137686849] Funding Source: UKRI
- Medical Research Council [MC_U137686849] Funding Source: researchfish
Contrary 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.
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