Department of Hematology, Xiangya Hospital, Central South University, Changsha, 410008, China.
Department of Nephropathy, Xiangya Hospital, Central South University, Changsha, 410008, China.
J Mater Sci Mater Med. 2018 May 9;29(5):66. doi: 10.1007/s10856-018-6054-4.
Anticoagulation therapy plays a vital role in the prevention of blood clot formation during hemodialysis and hemofiltration, especially for critical care patients. Here, we synthesized a novel argatroban (Arg)-modified polysulfone (PSf) membrane for anticoagulation. Arg was grafted onto the PSF membrane via chemical modification to increase membrane hydrophilicity. Protein adsorption, coagulation, as well as activation of platelets and complement systems were greatly reduced on the Arg-modified PSf membrane. Thus, the recalcification time and the activated partial thrombin time (APTT) were increased after the modification. In comparison with the pristine PSf membrane, the Arg-modified PSf membrane showed better hemocompatibility and anticoagulation properties, indicating its potential for applications in hemodialysis and hemofiltration. Modification of the PSf membrane has been investigated in attempts to further enhance the anticoagulation properties of the hemodialysis membranes, including a heparin-modified PSf membrane. However, heparin can inhibit plasma-free thrombin, and cause the occurrence of heparin-induced thrombocytopenia (HIT), which increases the risk of bleeding during dialysis in critical care patients. To address this problem, we modified PSf membrane with as a novel direct thrombin inhibitors, argatroban (Arg). It can reversibly bind to thrombin, inhibiting not only the plasma-free thrombin in the blood, but also clot-bound thrombin.
抗凝治疗在血液透析和血液滤过中防止血液形成血栓中起着至关重要的作用，尤其是对重症监护患者而言。在这里，我们合成了一种新型的阿加曲班（Arg）修饰的聚砜（PSf）膜用于抗凝。Arg 通过化学修饰接枝到 PSF 膜上以增加膜的亲水性。Arg 修饰的 PSf 膜上的蛋白质吸附、凝血以及血小板和补体系统的激活大大减少。因此，修饰后复钙时间和活化部分凝血活酶时间（APTT）增加。与原始 PSf 膜相比，Arg 修饰的 PSf 膜具有更好的血液相容性和抗凝性能，表明其在血液透析和血液滤过中的应用潜力。已经研究了 PSf 膜的修饰，以进一步增强血液透析膜的抗凝性能，包括肝素修饰的 PSf 膜。然而，肝素可以抑制血浆游离的凝血酶，并导致肝素诱导的血小板减少症（HIT）的发生，这增加了重症监护患者在透析过程中出血的风险。为了解决这个问题，我们用一种新型的直接凝血酶抑制剂阿加曲班（Arg）修饰了 PSf 膜。它可以可逆地与凝血酶结合，不仅抑制血液中的血浆游离凝血酶，还抑制结合在凝块上的凝血酶。
