P- 选择素/ PSGL-1 抑制剂与依诺肝素在静脉血栓溶解中的比较：一项荟萃分析。
P-selectin/ PSGL-1 inhibitors versus enoxaparin in the resolution of venous thrombosis: a meta-analysis.
机构信息
Jobst Vascular Surgery Research Laboratory, Section of Vascular Surgery, Cardiovascular Center, University of Michigan, Ann Arbor, Michigan 48109, USA.
出版信息
Thromb Res. 2010 Apr;125(4):e138-42. doi: 10.1016/j.thromres.2009.10.022. Epub 2009 Dec 4.
BACKGROUND
P-selectin antagonism has been shown to decrease thrombogenesis and inflammation in animal models of deep venous thrombosis (DVT).
OBJECTIVE
To determine the effectiveness of P-selectin inhibitors versus saline and enoxaparin in venous thrombus resolution in nonhuman primate models of venous thrombosis.
METHODS
Studies reporting vein re-opening, inflammation expressed as Gadolinium enhancement and coagulation parameters were searched in the literature and pooled into a meta-analysis using an inverse variance with random effects.
RESULTS
Five studies were identified comparing P-selectin/ PSGL-1 inhibitors versus saline or enoxaparin regarding venous thrombosis resolution. Vein re-opening was significantly higher on P-selectin/ PSGL-1 compounds, when compared to saline (Inverse Variance [IV] 95% CI; 44.37 [17.77-70.96], p=0.001, I(2)=97%) and similar to enoxaparin (IV 95% CI; 5.03 [-8.88-18.95], p=0.48, I(2)=41%). Inflammation, reflected as Gadolinium enhancement at magnetic resonance venography (MRV), was significantly decreased in the P-selectin treated group when compared to saline (IV 95% CI; -17.84 [-14.98-(-8.30)], p<0.00001, I(2)=80%). No significant differences on vein wall inflammation were observed between P-selectin/ PSGL-1 inhibitors and enoxaparin treated animals (IV95% CI; -3.59 [-10.67-3.48], p=0.32, I(2)=66%). In addition, there was no differences in the coagulation parameters (aPTT, TCT, BT, D-Dimer, fibrinogen, platelets) between P-selectin/ PSGL-1 inhibitors and enoxaparin (IV 95% CI; -1.12[-2.36-0.11], p=0.07, I(2)=92%), although there was a trend showing less of a prolongation in TCT with P-selectin/PSGL-1 inhibitors compared to enoxaparin (p<0.0001).
CONCLUSION
P-selectin antagonism successfully paralleled the low-molecular-weight-heparin enoxaparin, for the treatment of DVT in nonhuman primate models, by decreasing both thrombus burden and inflammation without causing any bleeding complications and without increasing coagulation times.
背景
已有研究表明，P-选择素拮抗作用可减少深静脉血栓形成（DVT）动物模型中的血栓形成和炎症反应。
目的
确定 P-选择素抑制剂与生理盐水和依诺肝素在非人类灵长类动物静脉血栓模型中对静脉血栓溶解的效果。
方法
检索文献中关于静脉再通、以钆增强表示的炎症以及凝血参数的研究，并使用逆方差随机效应进行荟萃分析。
结果
共确定了 5 项比较 P-选择素/ PSGL-1 抑制剂与生理盐水或依诺肝素在静脉血栓溶解方面的研究。与生理盐水相比，P-选择素/ PSGL-1 化合物组静脉再通率显著升高（逆方差[IV]95%置信区间；44.37 [17.77-70.96]，p=0.001，I(2)=97%），与依诺肝素相似（IV 95%置信区间；5.03 [-8.88-18.95]，p=0.48，I(2)=41%）。在 P-选择素治疗组，反映在磁共振静脉造影（MRV）上的钆增强炎症显著降低，与生理盐水相比（IV 95%置信区间；-17.84 [-14.98-（-8.30）]，p<0.00001，I(2)=80%）。与依诺肝素治疗动物相比，P-选择素/ PSGL-1 抑制剂对静脉壁炎症无显著影响（IV95%置信区间；-3.59 [-10.67-3.48]，p=0.32，I(2)=66%）。此外，与依诺肝素相比，P-选择素/ PSGL-1 抑制剂对凝血参数（aPTT、TCT、BT、D-二聚体、纤维蛋白原、血小板）无显著影响（IV 95%置信区间；-1.12[-2.36-0.11]，p=0.07，I(2)=92%），尽管有趋势表明 P-选择素/ PSGL-1 抑制剂与依诺肝素相比，TCT 的延长程度较低（p<0.0001）。
结论
P-选择素拮抗作用通过降低血栓负荷和炎症反应，成功地与低分子肝素依诺肝素相媲美，用于治疗非人类灵长类动物模型中的 DVT，而不会引起任何出血并发症，也不会增加凝血时间。
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