Okwusidi J I, Anvari N, Kulczycky M, Blajchman M A, Buchanan M R, Ofosu F A
Department of Pathology, McMaster University, Hamilton, Ontario, Canada.
J Lab Clin Med. 1991 May;117(5):359-64.
Three recent studies have reported that fibrin in solution significantly inhibits the ability of heparin to catalyze the inhibition of thrombin by antithrombin III. In addition, heparin inhibits the release of fibrinopeptide A by clot-bound thrombin less effectively than it inhibits the release of fibrinopeptide A by thrombin in solution. We have also reported that dermatan sulfate, which catalyzes thrombin inhibition by heparin cofactor II, inhibits thrombus growth in rabbits more effectively than heparin. Because the results of these studies suggest that fibrin inhibits the reactivity of thrombin with antithrombin III-heparin but not with heparin cofactor II-dermatan sulfate, we compared the relative catalytic effects of heparin and dermatan sulfate on thrombin inhibition in plasma, both in the presence and absence of fibrin. We quantitated the rates of thrombin inhibition by antithrombin III and heparin cofactor II by specific enzyme-linked immunosorbent assays. When it was generated, fibrin was kept in solution by adding 2 mmol/L Gly-Pro-Arg-Pro to plasma. Fibrinogen-fibrin reduced the reactivity of thrombin with plasma antithrombin III, both in the presence of and in the absence of heparin. In contrast, the catalytic action of dermatan sulfate on thrombin inhibition by plasma heparin cofactor II was unimpaired by fibrinogen-fibrin. Based on the ability of dermatan sulfate to inhibit thrombus growth in rabbits, failure of fibrinogen-fibrin to moderate the catalytic action of dermatan sulfate may account for its greater antithrombotic effectiveness relative to that of heparin.
最近的三项研究报告称，溶液中的纤维蛋白会显著抑制肝素催化抗凝血酶III抑制凝血酶的能力。此外，与抑制溶液中凝血酶释放纤维蛋白肽A相比，肝素抑制凝块结合的凝血酶释放纤维蛋白肽A的效果较差。我们还报告过，硫酸皮肤素可通过肝素辅因子II催化凝血酶抑制，其抑制兔血栓形成的效果比肝素更有效。由于这些研究结果表明，纤维蛋白会抑制凝血酶与抗凝血酶III - 肝素的反应性，但不会抑制其与肝素辅因子II - 硫酸皮肤素的反应性，因此我们比较了在有和没有纤维蛋白存在的情况下，肝素和硫酸皮肤素对血浆中凝血酶抑制的相对催化作用。我们通过特异性酶联免疫吸附测定法定量了抗凝血酶III和肝素辅因子II抑制凝血酶的速率。当生成纤维蛋白时，通过向血浆中添加2 mmol/L甘氨酰 - 脯氨酰 - 精氨酰 - 脯氨酸将其保持在溶液中。无论有无肝素存在，纤维蛋白原 - 纤维蛋白都会降低凝血酶与血浆抗凝血酶III的反应性。相比之下，纤维蛋白原 - 纤维蛋白不会削弱硫酸皮肤素对血浆肝素辅因子II抑制凝血酶的催化作用。基于硫酸皮肤素抑制兔血栓形成的能力，纤维蛋白原 - 纤维蛋白未能减弱硫酸皮肤素的催化作用可能解释了其相对于肝素具有更高的抗血栓形成有效性。
