Liu Ling, Ling Jing, Ma Zhenni, Yuan Quan, Pan Jun, Yang Huilin
Department of Orthopedics, Clinical Medical Research Center of Jiangsu Province, The First Affiliated Hospital of Soochow University, Suzhou, Jiangsu 215006, P.R. China.
Department of Hematology and Oncology, Children's Hospital of Soochow University, Suzhou, Jiangsu 215003, P.R. China.
Mol Med Rep. 2015 Apr;11(4):3015-20. doi: 10.3892/mmr.2014.3041. Epub 2014 Dec 3.
The glycoprotein, von Willebrand factor (VWF) is a carrier protein for factor VIII. When bound to platelets and the extracellular matrix, it promotes aggregation or adhesion of platelets to areas of vascular damage. A disintegrin and metalloproteinase with thrombospondin motif, member 13 (ADAMTS13) cleaves between the tyr1605 and met1606 residues in the central A2 domain of VWF decreasing its activity. The levels of ADAMTS13 and VWF are positively correlated with the risk of developing thrombosis and inversely correlated with the risk of bleeding. A total of 93 patients were observed, who underwent total hip arthroplasty or total knee arthroplasty. Blood samples were collected preoperatively and on postoperative days (PODs) 1, 2, 3, 5 and 7. Plasma levels of the ADAMTS13 antigen were determined using western blotting. The proteolytic activity was validated with the FRETS‑VWF73 assay. VWF:Ag and VWF:RCo activity were measured using an enzyme‑linked immunosorbent assay. Prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT), antithrombin III and plasma fibrinogen levels were measured on a Sysmex® CA500 system with corresponding reagents. D‑dimer levels were measured on a STA‑R fully automated coagulation analyzer. The results demonstrated that, the levels of VWF antigen and activity in the patient increased from postoperative day (POD) 1. By contrast, the level of the ADAMTS13 antigen and its activity in the patients decreased significantly. Starting on POD1, fibrinogen and D‑dimer levels increased. No significant changes were observed in PT, APTT and TT. It was concluded that the ADAMTS13 and VWF levels exhibited a marked association with thrombosis risk. The levels of ADAMTS13 and VWF may be potentially useful as markers for predicting thrombotic complications following arthroplasty and inhibiting the activity of VWF may be a novel prophylaxis to reduce postoperative deep venous thrombosis and pulmonary embolism.
糖蛋白血管性血友病因子(VWF)是因子VIII的载体蛋白。当与血小板和细胞外基质结合时,它促进血小板聚集或黏附于血管损伤部位。含血小板反应蛋白基序的解聚素和金属蛋白酶13(ADAMTS13)在VWF中央A2结构域的tyr1605和met1606残基之间切割,降低其活性。ADAMTS13和VWF的水平与血栓形成风险呈正相关,与出血风险呈负相关。共观察了93例行全髋关节置换术或全膝关节置换术的患者。术前及术后第1、2、3、5和7天采集血样。采用蛋白质印迹法测定血浆ADAMTS13抗原水平。用FRETS-VWF73检测法验证其蛋白水解活性。采用酶联免疫吸附测定法测定VWF:Ag和VWF:RCo活性。在Sysmex®CA500系统上使用相应试剂测定凝血酶原时间(PT)、活化部分凝血活酶时间(APTT)、凝血酶时间(TT)、抗凝血酶III和血浆纤维蛋白原水平。在STA-R全自动凝血分析仪上测定D-二聚体水平。结果表明,患者VWF抗原和活性水平从术后第1天开始升高。相比之下,患者ADAMTS13抗原水平及其活性显著降低。从术后第1天开始,纤维蛋白原和D-二聚体水平升高。PT、APTT和TT未观察到显著变化。得出结论,ADAMTS13和VWF水平与血栓形成风险显著相关。ADAMTS13和VWF水平可能作为预测关节置换术后血栓并发症的标志物,抑制VWF活性可能是预防术后深静脉血栓形成和肺栓塞的新方法。