Mauron T, Lämmle B, Wuillemin W A
Central Haematology Laboratory, Inselspital, University Hospital, Bern, Switzerland.
Thromb Haemost. 1998 Jul;80(1):82-6.
We investigated the influence of low molecular weight dextran sulfate (LMWdxs) and low molecular weight heparins (LMWH: dalteparin, enoxaparin and nadroparin) on the inhibition of FXIa by C1-inhibitor, alpha1-antitrypsin, alpha2-antiplasmin and antithrombin in a purified system and in plasma. The second order rate constant for inactivation of FXIa by C1-inhibitor, alpha1-antitrypsin, alpha2-antiplasmin, and antithrombin was 1.23, 0.056, 0.33 and 0.59 x 10(3) M(-1) s(-1), respectively. LMWdxs and LMWH dose-dependently increased the second order rate constant of the inactivation of FXIa by C1-inhibitor up to 39-fold. The second order rate constant of the inactivation of FXIa by antithrombin was increased up to 6-fold by LMWH, whereas LMWdxs had no effect. In plasma, FXIa was inactivated to about 50% by C1-inhibitor, while the other serpins contributed together to the remaining 50% of plasma's inhibitory capacity towards FXIa. In the presence of LMWdxs or LMWH, FXIa was inactivated in plasma to more than 90% by C1-inhibitor. LMWH at maximal therapeutic plasma levels enhanced the contribution of antithrombin to the inactivation of FXIa in plasma up to 5-fold. In conclusion, we found that the tested low molecular weight glycosaminoglycans dalteparin, enoxaparin and nadroparin and LMWdxs stimulate inactivation of FXIa by C1-inhibitor in a system using purified proteins as well as in plasma. Furthermore, LMWH but not LMWdxs slightly enhanced FXIa inhibition by antithrombin.
我们研究了低分子量硫酸葡聚糖（LMWdxs）和低分子量肝素（LMWH：达肝素、依诺肝素和那屈肝素）在纯化系统和血浆中对C1抑制剂、α1抗胰蛋白酶、α2抗纤溶酶和抗凝血酶抑制因子XIa（FXIa）的影响。C1抑制剂、α1抗胰蛋白酶、α2抗纤溶酶和抗凝血酶使FXIa失活的二级速率常数分别为1.23、0.056、0.33和0.59×10³ M⁻¹ s⁻¹。LMWdxs和LMWH呈剂量依赖性地将C1抑制剂使FXIa失活的二级速率常数提高至39倍。LMWH使抗凝血酶使FXIa失活的二级速率常数提高至6倍，而LMWdxs则无此作用。在血浆中，C1抑制剂使FXIa失活约50%，而其他丝氨酸蛋白酶抑制剂共同发挥作用，使血浆对FXIa的抑制能力达到其余的50%。在LMWdxs或LMWH存在的情况下，C1抑制剂在血浆中将FXIa失活至90%以上。最大治疗血浆水平的LMWH使抗凝血酶对血浆中FXIa失活的贡献增强至5倍。总之，我们发现，所测试的低分子量糖胺聚糖达肝素、依诺肝素、那屈肝素和LMWdxs在使用纯化蛋白的系统以及血浆中均能刺激C1抑制剂使FXIa失活。此外，LMWH而非LMWdxs能轻微增强抗凝血酶对FXIa的抑制作用。
