Nossel H L, Rubin H, Drillings M, Hsieh R
J Clin Invest. 1968 May;47(5):1172-80. doi: 10.1172/JCI105806.
A method for studying inhibitors of the contact stages of blood coagulation is described. A number of positively charged substances were shown to inhibit the contact stages. The inhibitory substances include spermine, cytochrome c, ribonuclease, and lysozyme. The inhibitory effect of these substances was neutralized by the addition of an activated plasma thromboplastin antecedent, factor XI, (PTA) fraction. Other positively charged substances including protamine, hexadimethrine, polylysine, polyornithine, methylene blue, and ortho-toluidine blue also inhibited the contact stages of coagulation, but the inhibitory effect on coagulation was not neutralized by the activated PTA fraction. Negatively charged substances such as heparin and insulin did not inhibit the contact stages of coagulation. Cytochrome c inhibited Celite adsorption of a partially purified Hageman factor fraction, and cytochrome, ribonuclease, spermine, and lysozome inhibited the adsorption of Hageman factor from PTA-deficient plasma. Very much smaller quantities of Celite completely adsorbed Hageman factor from the fraction rather than from whole plasma, which suggested the possibility that plasma contains an inhibitor or inhibitors of Hageman factor adsorption. Furthermore cytochrome c, spermine, ribonuclease, and lysozyme inhibited the coagulant activity of the following activators of the Hageman and PTA factors: Celite, kaolin, sodium stearate, ellagic acid, and skin. It is suggested that negatively charged sites on these activators are critical for adsorption and activation and that inhibition results from neutralization of the negatively charged sites by the adsorbed inhibtor. Tests with polylysine polymers indicate that inhibitory activity is directly related to molecular size over the molecular weight range of 4000 to 100,000.
本文描述了一种研究血液凝固接触阶段抑制剂的方法。已证明许多带正电荷的物质可抑制接触阶段。这些抑制物质包括精胺、细胞色素c、核糖核酸酶和溶菌酶。加入活化的血浆促凝血酶原激酶前体（因子XI，PTA）组分可中和这些物质的抑制作用。其他带正电荷的物质，包括鱼精蛋白、六甲双铵、聚赖氨酸、聚鸟氨酸、亚甲蓝和邻甲苯胺蓝，也抑制凝血的接触阶段，但活化的PTA组分不能中和其对凝血的抑制作用。带负电荷的物质，如肝素和胰岛素，不抑制凝血的接触阶段。细胞色素c抑制硅藻土对部分纯化的Hageman因子组分的吸附，细胞色素、核糖核酸酶、精胺和溶菌酶抑制从缺乏PTA的血浆中吸附Hageman因子。极少量的硅藻土就能完全从该组分中吸附Hageman因子，而不是从全血中，这表明血浆中可能含有一种或多种Hageman因子吸附抑制剂。此外，细胞色素c、精胺、核糖核酸酶和溶菌酶抑制以下Hageman因子和PTA因子激活剂的凝血活性：硅藻土、高岭土、硬脂酸钠、鞣花酸和皮肤。有人认为，这些激活剂上的带负电荷位点对于吸附和激活至关重要，而抑制作用是由于吸附的抑制剂中和了带负电荷位点所致。对聚赖氨酸聚合物的测试表明，在分子量4000至100,000的范围内，抑制活性与分子大小直接相关。
