Clemens R, Lorenz R, Pukrittayakamee S, Punpoowang B, Vanijanonta S, Charoenlarp P
Faculty of Tropical Medicine, Mahidol University, Bangkok, Thailand.
Southeast Asian J Trop Med Public Health. 1995 Mar;26(1):143-8.
The procoagulant activities of Russell's viper venom were assessed in an in vitro whole blood model. Sequential samplings showed that the generation of fibrinopeptide A (FPA), a marker of thrombin activity, and platelet factor 4 (PF4), a marker of platelet activity, exhibited bi-phasic kinetics with an initial slow phase followed by a rapid phase of secretion. In the presence of Russell's viper venom, the generation of both FPA and PF4 was accelerated with the bi-phasic kinetics of PF4 being maintained while that of FPA completely disappeared. Administration of either antivenom (1,600 ng) or 10 IU antithrombin III (AT-III) had no antagonistic effect against the venom but combination of both resulted in a significant prolongation of both FPA and PF4 release (p < 0.05). High dose AT-III (20 IU) resulted in normalization of both FPA and PF4 kinetics and serial levels of both parameters were lower than those treated with the combined regimen, although these were not statistically significant. Unlike the untreated venom activated whole blood, there was no clot formation following treatment with either the combined regimen or high dose AT-III. The results of this study suggested that the effect of Russell's viper venom on the clotting cascade is more potent and direct than that on platelet activity. There were complementary effects between antivenom and AT-III is controlling of both FPA and PF4 release induced by the venom. Furthermore, in this in vitro experiment, AT-III alone when administered in a sufficient dose, abolished the procoagulant effects of Russell's viper venom.
在体外全血模型中评估了锯鳞蝰蛇毒的促凝血活性。连续取样显示，凝血酶活性标志物纤维蛋白肽A（FPA）和血小板活性标志物血小板因子4（PF4）的生成呈现双相动力学，初始为缓慢阶段，随后是快速分泌阶段。在锯鳞蝰蛇毒存在的情况下，FPA和PF4的生成均加速，PF4的双相动力学得以维持，而FPA的双相动力学则完全消失。给予抗蛇毒血清（1600 ng）或10 IU抗凝血酶III（AT-III）对蛇毒均无拮抗作用，但两者联合使用可显著延长FPA和PF4的释放时间（p < 0.05）。高剂量AT-III（20 IU）可使FPA和PF4的动力学恢复正常，且这两个参数的系列水平均低于联合治疗组，尽管差异无统计学意义。与未处理的蛇毒激活的全血不同，联合治疗组或高剂量AT-III治疗后均未形成凝块。本研究结果表明，锯鳞蝰蛇毒对凝血级联反应的影响比对血小板活性的影响更强烈、更直接。抗蛇毒血清和AT-III在控制蛇毒诱导的FPA和PF4释放方面具有互补作用。此外，在本体外实验中，单独给予足够剂量的AT-III可消除锯鳞蝰蛇毒的促凝血作用。
