Bleeding diathesis due to decreased functional activity of type 1 plasminogen activator inhibitor.
Bleeding diathesis due to decreased functional activity of type 1 plasminogen activator inhibitor.
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由于 1 型纤溶酶原激活剂抑制剂的功能活性降低而导致出血素质。
DOI：
10.1172/jci114076
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发表时间：
1989
期刊：
影响因子：
--
通讯作者：
Levitt,LJ
中科院分区：
文献类型：
--
作者：
Schleef,RR;Higgins,DL;Pillemer,E;Levitt,LJ
我们评估了一位老年患者，该患者在手术或创伤后有终生严重出血史，并且有持续纤溶亢进的证据。常规凝血检查正常。血清纤溶酶原（40%，正常72-128%）和α2-抗纤溶酶（55%，正常70-145%）活性降低。优球蛋白凝块溶解异常缩短（50 分钟），并在体外用ε-氨基己酸 (EACA) 使其正常化。该患者接受了 EACA 治疗，出血迅速停止。通过双位点免疫放射测定 (IRMA) 检测，患者血清中组织纤溶酶原激活剂 (t-PA) 水平正常（4.7 ng/ml，对照 3.5-7.2）。通过将 125I 标记的 t-PA 与全血或血清一起孵育，然后进行 SDS-PAGE 和放射自显影以鉴定所得的蛋白酶/蛋白酶抑制剂复合物，评估患者纤溶抑制剂活性。与从正常供体获得的血液样本相比，患者血浆和血清显示速效纤溶酶原激活剂抑制剂与 125I 标记的 t-PA 的结合减少。免疫沉淀实验表明患者血清中 1 型纤溶酶原激活剂抑制剂 (PAI-1) 与 125I 标记的 t-PA 之间的复合物形成减少。使用功能性 IRMA 定量 PAI-1 与固定化 t-PA 的结合，证实血清中患者 PAI-1 活性较低（0.36 U/ml，对照 0.87-1.81；n = 3）和血小板裂解物。然而，经 IRMA 分析后，患者血清 PAI-1 抗原在正常范围内（31.8 ng/ml，对照 19.6-42.2）；该结果通过蛋白质印迹在血清和血小板中得到证实（n = 3）。使用纯化的 PAI-1 以及患者和对照血清的混合实验没有显示出 PAI-1 抑制剂的证据。我们得出结论，该患者的出血素质是由于纤溶亢进和 PAI-1 缺陷所致。该患者首次证明体内 PAI-1 活性降低与止血紊乱之间存在联系，并支持 PAI-1 在控制体内纤维蛋白溶解中的作用。
We evaluated an elderly patient with a lifelong history of severe bleeding after surgery or trauma and with evidence of persistent hyperfibrinolysis. Routine coagulation studies were normal. Serum plasminogen (40%, normal 72-128%) and alpha 2-antiplasmin (55%, normal 70-145%) activities were decreased. Euglobulin clot lysis was abnormally shortened (50 min) and normalized in vitro with epsilon-aminocaproic acid (EACA). The patient was treated with EACA with prompt cessation of bleeding. Patient tissue-plasminogen activator (t-PA) levels in serum were normal (4.7 ng/ml, control 3.5-7.2) as detected by a two-site immunoradiometric assay (IRMA). Patient fibrinolytic inhibitor activities were assessed by incubating 125I-labeled t-PA with either whole blood or serum followed by SDS-PAGE and autoradiography to identify the resultant protease/protease inhibitor complexes. In comparison to blood samples obtained from normal donors, patient plasma and serum demonstrated reduced binding of a fast-acting plasminogen activator inhibitor to 125I-labeled t-PA. Immunoprecipitation experiments indicated diminished complex formation between type 1 plasminogen activator inhibitor (PAI-1) in patient serum and 125I-labeled t-PA. Low patient PAI-1 activity was confirmed in serum (0.36 U/ml, control 0.87-1.81; n = 3) and in platelet lysates using a functional IRMA to quantitate PAI-1 binding to immobilized t-PA. However, patient serum PAI-1 antigen was within the normal range when analyzed by IRMA (31.8 ng/ml, control 19.6-42.2); this result was confirmed in both serum and platelets by Western blot (n = 3). Mixing experiments using purified PAI-1 as well as patient and control sera did not show evidence for an inhibitor against PAI-1. We conclude that this patient's bleeding diathesis was due to hyperfibrinolysis and defective PAI-1. This patient provides the first demonstration of a link between decreased in vivo PAI-1 activity and disordered hemostasis, and supports a role for PAI-1 in control of vivo fibrinolysis.Images
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坂田洋一：临床研究杂志。
DOI：
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发表时间：
--
期刊：
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作者：
通讯作者：
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DOI：
10.1016/s0021-9258(17)42691-3
发表时间：
1984-12
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
J. V. van Mourik;D. Lawrence;D. Loskutoff
通讯作者：
J. V. van Mourik;D. Lawrence;D. Loskutoff
内皮细胞、血小板、血清和血浆中的主要纤溶酶原激活剂抑制剂与免疫学相关。
DOI：
10.1073/pnas.82.24.8710
发表时间：
1985
影响因子：
11.1
作者：
Erickson,LA;Hekman,CM;Loskutoff,DJ
通讯作者：
Loskutoff,DJ
DOI：
10.1016/s0021-9258(18)60636-2
发表时间：
1988-04
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Raymond R. SchleefSS;Michael P. BevilacqualI;Michael Sawdeys;M. Gimbrone;David;LoskutoffS
通讯作者：
Raymond R. SchleefSS;Michael P. BevilacqualI;Michael Sawdeys;M. Gimbrone;David;LoskutoffS
影响因子：
20.3
作者：
K. Bauer;K. Bauer;R. Rosenberg;R. Rosenberg
通讯作者：
K. Bauer;K. Bauer;R. Rosenberg;R. Rosenberg