Stief T W, Weippert M, Kretschmer V, Renz H
Department of Clinical Chemistry and Molecular Diagnostics, Hospital of Philipps University, D-35033 Marburg, Germany.
Thromb Res. 2001 Nov 15;104(4):265-74. doi: 10.1016/s0049-3848(01)00368-1.
The diagnosis and the therapy of in vivo hemostasis activation is of great clinical importance. Artefactual changes of the hemostasis (i.e., coagulation or fibrinolysis) in vitro have to be prevented. Usual in vitro anticoagulation by sodium citrate does not fully inhibit coagulation--or fibrinolysis--activation. Therefore, there is need for a simple physiologic inhibitor of hemostasis activation both in diagnosis and therapy of hemostasis activation.
Whole blood clotting time (WBCT), prothrombin time (PT), activated partial thromboplastin time (APTT), in vitro bleeding test closure time (IVBT-CT), and whole blood aggregometry (WBA) were determined in normal human blood or plasma, supplemented with increasing concentrations of L-arginine or guanidine.
Arginine in concentrations of 5-100 mM inhibited the WBCT, PT, APTT, IVBT-CT, and WBA. Arginine (50 mM) resulted in a two-fold prolongation of WBCT, PT, or IVBT-CT (the anti-epinephrine action is superior to the anti-ADP action), a four-fold prolongation of APTT or a 60% inhibition of WBA.
L-Arginine (or guanidine) inhibited the activation of hemostasis. Arginine might be used as hemostasis stabilizer both in the diagnosis and therapy of hemostasis activation. The usage of arginine as an in vitro hemostasis inhibitor might be indicated in the diagnosis of hemostasis activation, as occurring in pharmacological thrombolysis or disseminated intravascular coagulation (DIC). The storage of blood or blood products might be improved by arginine stabilization. The amino acid (and nitric oxide precursor) L-arginine could be an interesting new pharmacologic agent to inhibit a pathologic hemostasis activation.
体内止血激活的诊断与治疗具有重要的临床意义。必须防止体外止血(即凝血或纤溶)的人为变化。常规的柠檬酸钠体外抗凝不能完全抑制凝血或纤溶激活。因此,在止血激活的诊断和治疗中都需要一种简单的生理性止血激活抑制剂。
在正常人血液或血浆中加入浓度递增的L-精氨酸或胍,测定全血凝固时间(WBCT)、凝血酶原时间(PT)、活化部分凝血活酶时间(APTT)、体外出血试验封闭时间(IVBT-CT)和全血凝集试验(WBA)。
浓度为5-100 mM的精氨酸可抑制WBCT、PT、APTT、IVBT-CT和WBA。精氨酸(50 mM)可使WBCT、PT或IVBT-CT延长两倍(抗肾上腺素作用优于抗ADP作用),使APTT延长四倍或使WBA抑制60%。
L-精氨酸(或胍)可抑制止血激活。精氨酸可作为止血激活诊断和治疗中的止血稳定剂。在药理学溶栓或弥散性血管内凝血(DIC)等止血激活的诊断中,可能需要使用精氨酸作为体外止血抑制剂。精氨酸稳定作用可能会改善血液或血液制品的储存。氨基酸(一氧化氮前体)L-精氨酸可能是一种新型的抑制病理性止血激活的有趣药物。