Liebman H A, Comenzo R, Allen S T, Dilorio J M
William B. Castle Hematology Research Laboratory, Department of Medicine, Boston City Hospital, MA 02118.
Am J Hematol. 1991 Sep;38(1):24-9. doi: 10.1002/ajh.2830380105.
The isolation and partial characterization of a novel anticoagulant from the plasma of a patient with metastatic prostate cancer is described. The patient had a prolonged activated partial thromboplastic time, prothrombin time and thrombin time which did not correct by mixing with normal plasma. The reptilase time was normal and the prolonged thrombin time was corrected with protamine sulfate suggesting a heparin-like anticoagulant. A glycosaminoglycan anticoagulant (GAC) was isolated from the patient's plasma. The inhibitory activity of the GAC was destroyed by treatment with chondroitinase ABC. The GAC migrated on agarose gel electrophoresis between keratin sulfate and heparan sulfate. Purified GAC possessed only 2% (W/W) of the antithrombin III cofactor activity of porcine heparin. In assays using purified fibrinogen, the GAC was shown to directly inhibit fibrinogen proteolysis by thrombin. It is concluded that this glycosaminoglycan anticoagulant directly inhibits thrombin clotting of fibrinogen and is a new mechanism for abnormal hemostatic assays in cancer.
本文描述了从一名转移性前列腺癌患者血浆中分离出一种新型抗凝剂并对其进行部分特性鉴定的过程。该患者活化部分凝血活酶时间、凝血酶原时间和凝血酶时间延长，与正常血浆混合后未得到纠正。蝰蛇毒时间正常，延长的凝血酶时间用硫酸鱼精蛋白纠正，提示存在类肝素抗凝剂。从患者血浆中分离出一种糖胺聚糖抗凝剂（GAC）。用软骨素酶ABC处理后，GAC的抑制活性被破坏。GAC在琼脂糖凝胶电泳上的迁移位置介于硫酸角质素和硫酸乙酰肝素之间。纯化的GAC仅具有猪肝素抗凝血酶III辅因子活性的2%（W/W）。在使用纯化纤维蛋白原的测定中，GAC被证明可直接抑制凝血酶对纤维蛋白原的蛋白水解作用。得出的结论是，这种糖胺聚糖抗凝剂直接抑制纤维蛋白原的凝血酶凝血作用，是癌症患者止血检测异常的一种新机制。
