New devices in anticoagulant therapy for massive hepatic necrosis through sinusoidal fibrin deposition

大面积肝坏死是暴发性病毒性肝炎的特征，由于枯否细胞和窦状隙内皮细胞之间的凝血平衡紊乱而导致微循环障碍。与其他器官的血管相比，肝血窦中的抗凝活性降低，这是由于内皮细胞上组织因子途径抑制物（TFPI）和血栓调节蛋白（TM）的表达无或极低的结果。因此，TFPI和TM的替代可能是一个强大的治疗这种肝损伤。当大鼠静脉注射重组人TFPI时，TFPI在注射后迅速从循环中消失，并在窦内皮细胞和肝细胞微绒毛表面检测到TFPI，这表明TFPI可能仅在窦壁上起抗凝作用。TM被设计为通过甘露糖受体作为靶向基因表达来增强其对窦状内皮细胞的作用。门静脉内注射表面含有甘露糖和FITC的miscell在窦壁的衬里上产生荧光产物。这些针对肝窦壁的抗凝装置可能是暴发性病毒性肝炎的治疗候选者，一般出血的不良反应最小。

Massive hepatic necrosis, characteristic of fulminant viral hepatitis, occurs as a result of microcirculatory disturbance due to deranged blood coagulation equilibrium between Kupffer cells and sinusoidal endothelial cells. Anticoagulant activity in the hepatic sinusoids was decreased compared to the vessels in other organs as a consequence of no or extremely reduced expressionof tissue factor pathway inhibitor (TFPI) and thrombomodulin (TM) on endothelial cells. Thus, the replacement of TFPI and TM might be a powerful therapy for such liver injury. When rats received recombinant human TFPI intravenously, TFPI disappeared from the circulation rapidly after the injection, and were detected on the surface of sinusoidal endothelial cells and microvilli of hepatocytes, suggesting that TFPI may act as an anticoagulant exclusively on the sinusoidal walls. TM was designed to exert its action enhanced on sinusoidal endothelial cells by expression as a targeting gene through mannose receptors. Intraportal injection of miscells containing mannose and FITC on the surface produced fluorescence products on the lining of sinusoidal walls. These anticoagulant devices targeting hepatic sinusoidal walls may be therapeutic candidates for fulminant viral hepatitis with minimal adverse effects of general bleeding.