McBane Robert D, Leadley Robert J, Baxi Sangita M, Karnicki Krzysztof, Wysokinski Waldemar
Section of Hematology Research, Mayo Clinic, 200 First Street, Rochester, MN 55905, USA.
Arterioscler Thromb Vasc Biol. 2008 Mar;28(3):413-8. doi: 10.1161/ATVBAHA.107.158691. Epub 2007 Dec 20.
The clinical use of venous stents is increasing dramatically. Although antiplatelet agents are required for arterial stent patency, optimal thrombo-prophylaxis after venous stenting remains undefined. To address this issue, PD0348292, a direct Factor Xa inhibitor, was compared with antiplatelet therapy in a porcine venous stent model.
Four hours before stent deployment, pigs (n=5 to 6 per group) received oral PD0348292 at 0.4, 0.9, 4.3 mg/kg, or 0.4 mg/kg plus aspirin (325 mg). Aspirin, clopidogrel (75 mg), aspirin plus clopidogrel, or vehicle (n=10) were administered daily for 2 days before the procedure. Two hours after stent placement, thrombi were quantified by autologous (111)In-platelet content and weights. Thrombus weight and platelet deposition were significantly reduced by PD0348292 at 0.4 (49+/-79 mg and 110+/-145x10(6)/cm2), 0.9 (5+/-6 mg and 107+/-128x10(6)/cm2), 4.3 mg/kg (0+/-0 mg and 87+/-125x10(6)/cm2), and PD348292 plus aspirin (20+/-40 mg and 157+/-70x10(6)/cm2) compared with vehicle (402+/-226 mg; 584+/-454x10(6)/cm2). Despite prolonging bleeding times and inhibiting platelet aggregation, neither aspirin (567+/-683 mg and 533+/-622x10(6)/cm2), clopidogrel (404+/-349 mg and 178+/-101x10(6)/cm2), nor aspirin plus clopidogrel (247+/-261 mg and 231+/-266x10(6)/cm2) significantly decreased stent thrombosis.
PD0348292 completely inhibited thrombosis after venous stenting. Platelet accretion in these venous thrombi appear to involve pathways distinct from arachidonate metabolism or ADP P2Y12 receptor activation.
静脉支架的临床应用正在急剧增加。虽然动脉支架通畅需要抗血小板药物，但静脉支架置入术后的最佳血栓预防方法仍不明确。为解决这一问题，在猪静脉支架模型中，将直接Xa因子抑制剂PD0348292与抗血小板治疗进行了比较。
在支架置入前4小时，猪（每组n = 5至6只）分别接受0.4、0.9、4.3mg/kg的口服PD0348292，或0.4mg/kg加阿司匹林（325mg）。在手术前2天，每天给予阿司匹林、氯吡格雷（75mg）、阿司匹林加氯吡格雷或赋形剂（n = 10）。支架置入后2小时，通过自体（111）In-血小板含量和重量对血栓进行定量。与赋形剂组（402±226mg；584±454x10(6)/cm2）相比，0.4mg/kg（49±79mg和110±145x10(6)/cm2）、0.9mg/kg（5±6mg和107±128x10(6)/cm2）、4.3mg/kg（0±0mg和87±125x10(6)/cm2）的PD0348292以及PD348292加阿司匹林组（20±40mg和157±70x10(6)/cm2）的血栓重量和血小板沉积均显著减少。尽管延长了出血时间并抑制了血小板聚集，但阿司匹林（567±683mg和533±622x10(6)/cm2）、氯吡格雷（404±349mg和178±101x10(6)/cm2）以及阿司匹林加氯吡格雷组（247±261mg和231±266x10(6)/cm2）均未显著降低支架血栓形成。
PD0348292完全抑制了静脉支架置入后的血栓形成。这些静脉血栓中的血小板积聚似乎涉及不同于花生四烯酸代谢或ADP P2Y12受体激活的途径。
