Sultan Y, Harris A, Strauch G, Venot A, De Lauture D
Laboratoire d'Hémostase et Institut de Recherche Thérapeutique, Hôpital Cochin, Paris, France.
J Lab Clin Med. 1988 Jun;111(6):645-53.
Fibrinolysis dependent on the release of tissue plasminogen activator (t-PA) can only be explored after stimulation eliciting the release of t-PA from endothelial cells. The choice of the stimulus and test assay is of utmost importance in discriminating patients at risk for persistent thrombosis and in identifying acquired or genetic abnormalities of t-PA synthesis or release from endothelial cells in pathologic conditions. The present study was designed to compare the efficacy and reproducibility of the fibrinolytic response to desmopressin acetate (deamino-8-D-argininevasopressin) (DDAVP) by use of various routes of administration with the response to the venous occlusion test. Nine healthy male volunteers were randomly administered intravenous desmopressin acetate, intranasal drops and intranasal spray. The results from tests of euglobulin lysis time, t-PA activity, t-PA antigen levels, and t-PA fast-acting inhibitor (plasminogen activator inhibitor [PAI]) level were compared with those obtained after venous occlusion. The only test that elicited the release of free t-PA activity in the circulation in all volunteers was the intravenous administration of 0.4 microgram/kg desmopressin acetate, and the most reliable test assay was t-PA activity measured in the euglobulin fraction of plasma. Intravenous desmopressin acetate induced the release of large amounts of t-PA in most cases and caused a significant fall in PAI. Other routes of administration of desmopressin acetate, along with venous occlusion, identified many nonresponders who proved to be false negative. The relevance of these data was demonstrated in a study in nine patients with thromboembolic phenomenon or related disorders.(ABSTRACT TRUNCATED AT 250 WORDS)
依赖组织型纤溶酶原激活物(t-PA)释放的纤维蛋白溶解作用,只有在刺激引发内皮细胞释放t-PA后才能进行研究。在鉴别有持续性血栓形成风险的患者以及识别病理状态下t-PA合成或内皮细胞释放的获得性或遗传性异常时,刺激物和检测方法的选择至关重要。本研究旨在比较通过不同给药途径给予醋酸去氨加压素(去氨基-8-D-精氨酸加压素)(DDAVP)后纤溶反应的疗效和可重复性与静脉闭塞试验的反应。9名健康男性志愿者被随机给予静脉注射醋酸去氨加压素、滴鼻剂和鼻喷雾剂。将优球蛋白溶解时间、t-PA活性、t-PA抗原水平和t-PA快速作用抑制剂(纤溶酶原激活物抑制剂[PAI])水平的检测结果与静脉闭塞后获得的结果进行比较。在所有志愿者中,唯一能引发循环中游离t-PA活性释放的检测是静脉注射0.4微克/千克醋酸去氨加压素,最可靠的检测方法是测定血浆优球蛋白部分中的t-PA活性。静脉注射醋酸去氨加压素在大多数情况下诱导大量t-PA释放,并导致PAI显著下降。醋酸去氨加压素的其他给药途径以及静脉闭塞试验,识别出许多无反应者,这些人被证明为假阴性。这些数据的相关性在一项对9名有血栓栓塞现象或相关疾病患者的研究中得到了证实。(摘要截短至250字)