无需抗凝治疗，通过抑制炎症来预防静脉血栓形成。

Venous thrombosis prophylaxis by inflammatory inhibition without anticoagulation therapy.

作者信息

Wakefield T W, Strieter R M, Schaub R, Myers D D, Prince M R, Wrobleski S K, Londy F J, Kadell A M, Brown S L, Henke P K, Greenfield L J

机构信息

Jobst Vascular Surgery Laboratory, Section of Vascular Surgery, Department of Surgery, University of Michigan Medical Center, Ann Arbor, MI 48109-0329, USA.

出版信息

J Vasc Surg. 2000 Feb;31(2):309-24. doi: 10.1016/s0741-5214(00)90162-9.

DOI:10.1016/s0741-5214(00)90162-9

PMID:10664500

Abstract

OBJECTIVE

This study was performed to determine the effectiveness of recombinant P-selectin glycoprotein ligand Ig (rPSGL-Ig) pretreatment to decrease thrombosis and inflammation in experimental venous thrombosis. rPSGL-Ig, a unique mucin-like glycoprotein, has a high affinity for P-selectin.

METHODS

Twelve juvenile baboons underwent inferior vena cava (IVC) thrombosis with temporary 6-hour IVC balloon occlusion. Before balloon placement, the animals received rPSGL-Ig (4 mg/kg; n = 8) or saline solution for control (n = 4). The animals underwent evaluation with duplex ultrasound scan imaging, magnetic resonance venography (MRV), phlebography, coagulation profile, and tissue analysis at death for cytokines and vein wall leukocyte morphometrics. With the MRV results, thrombus development, thrombus resolution, and inflammation (gadolinium; square millimeters of enhancement) were assessed.

RESULTS

Each animal provided two time points for evaluation (days 2 and 6 after balloon occlusion). A significant decrease in IVC thrombosis between balloons was found in the rPSGL-Ig animals (1 of 16) versus the control animals (5 of 8; P <.01). The MRV results showed significantly less enhancement in the rPSGL-Ig animals at days 2 and 6 (P <.05). Spontaneous thrombus resolution (including balloon sites) was significantly greater from day 2 to day 6 in the rPSGL-Ig animals versus the control animals (23% vs 2%; P <.001), without pulmonary embolism. Lower interleukin-8, platelet factor IV, and monocyte chemotactic protein-1 levels were found in rPSGL-Ig vein walls without significant differences in vein wall leukocyte morphometrics. There were significantly lower D-dimer levels in the rPSGL-Ig-treated animals (P <.05), but there were no differences in measurements of coagulation. Adequate circulating rPSGL-Ig levels were documented.

CONCLUSION

Pretreatment with rPSGL-Ig results in: (1) a significant inhibition of thrombosis and vein wall inflammation; (2) a decrease in vein wall cytokine expression; and (3) a promotion of thrombus resolution. Inflammatory inhibition by rPSGL-Ig without anticoagulation therapy provides effective venous thrombosis prophylaxis in experimental venous thrombosis.

摘要

目的

本研究旨在确定重组P-选择素糖蛋白配体Ig（rPSGL-Ig）预处理对减少实验性静脉血栓形成和炎症的有效性。rPSGL-Ig是一种独特的黏蛋白样糖蛋白，对P-选择素有高亲和力。

方法

12只幼年狒狒通过下腔静脉（IVC）6小时临时球囊闭塞形成IVC血栓。在放置球囊前，动物接受rPSGL-Ig（4mg/kg；n = 8）或生理盐水作为对照（n = 4）。动物在死亡时接受双功超声扫描成像、磁共振静脉造影（MRV）、静脉造影、凝血指标评估以及组织分析，以检测细胞因子和静脉壁白细胞形态学。根据MRV结果，评估血栓形成、血栓溶解和炎症（钆；增强的平方毫米数）情况。

结果

每只动物提供两个评估时间点（球囊闭塞后第2天和第6天）。与对照动物（8只中的5只）相比，rPSGL-Ig处理的动物在球囊间IVC血栓形成显著减少（16只中的1只；P <.01）。MRV结果显示，rPSGL-Ig处理的动物在第2天和第6天的增强明显较少（P <.05）。与对照动物相比，rPSGL-Ig处理的动物从第2天到第6天的自发血栓溶解（包括球囊部位）显著更多（23%对2%；P <.001），且无肺栓塞。rPSGL-Ig处理的静脉壁中白细胞介素-8、血小板因子IV和单核细胞趋化蛋白-1水平较低，静脉壁白细胞形态学无显著差异。rPSGL-Ig处理的动物D-二聚体水平显著较低（P <.05），但凝血指标测量无差异。记录到足够的循环rPSGL-Ig水平。