Kojima S, Shiba M, Kuramochi M, Yamamoto A
Department of Clinical Research, Tohsei National Hospital, Shizuoka, Japan.
Artif Organs. 1995 Feb;19(2):135-9. doi: 10.1111/j.1525-1594.1995.tb02302.x.
Dextran-sulfate (DS) cellulose used for low-density lipoprotein (LDL) apheresis seems to be a weak activator of the contact phase of the intrinsic coagulation pathway because the surface of this substance has negative charges. Heparin, a commonly used anticoagulant, has no effect on this process whereas the process is inhibited by a newly developed anticoagulant, nafamostat mesilate (NM). The effects on bradykinin generation were compared between heparin and NM. Five patients with severe hypercholesterolemia were treated with LDL apheresis using either heparin or NM on a different day. During apheresis with heparin, factor XII, high molecular weight kininogen, and prekallikrein were markedly decreased by passing through the DS column. A distinct generation of bradykinin was observed by passing plasma through the DS column, and this led to the rise of bradykinin levels from 12 +/- 5 (mean +/- SE) to 72 +/- 14 pg/ml after treatment of 1,000 ml of plasma. NM suppressed almost completely the rise of bradykinin levels. Although blood pressure was apt to decrease during apheresis with heparin, there was no significant difference in blood pressure between heparin and NM. Since an angiotensin-converting enzyme inhibitor may lead to a marked rise in blood levels of bradykinin by suppressing its degradation, the use of NM is recommended for apheresis in patients taking this drug.
用于低密度脂蛋白（LDL）单采术的硫酸葡聚糖（DS）纤维素似乎是内源性凝血途径接触相的弱激活剂，因为该物质表面带有负电荷。常用抗凝剂肝素对这一过程无影响，而一种新开发的抗凝剂甲磺酸萘莫司他（NM）可抑制该过程。比较了肝素和NM对缓激肽生成的影响。5例严重高胆固醇血症患者在不同日期分别使用肝素或NM进行LDL单采术治疗。在使用肝素进行单采术期间，因子Ⅻ、高分子量激肽原和前激肽释放酶通过DS柱后显著减少。血浆通过DS柱后可观察到明显的缓激肽生成，在处理1000ml血浆后，缓激肽水平从12±5（平均值±标准误）上升至72±14pg/ml。NM几乎完全抑制了缓激肽水平的升高。虽然在使用肝素进行单采术期间血压容易降低，但肝素和NM之间的血压无显著差异。由于血管紧张素转换酶抑制剂可能通过抑制缓激肽降解导致其血药浓度显著升高，因此建议在服用该药物的患者进行单采术时使用NM。
