Hilgard P
Br J Cancer. 1973 Nov;28(5):429-35. doi: 10.1038/bjc.1973.168.
After the intravenous injection of Walker 256 tumour cells into rats the platelet count decreased rapidly and remained low during the following period of observation. The platelet decrease was closely related to the number of cells injected. Intra-arterial tumour cell injections required a considerably higher tumour cell count to produce a comparable thrombocytopenia. Non-viable tumour cells and tumour cell fragments induced a similar decrease of circulating platelets. Neither viable tumour cells nor tumour cell fragments aggregated rat platelets in vitro. The presence of fibrin monomers in tumour cell injected animals suggested intravascular fibrin deposition; the plasma fibrinogen level, however, did not decrease significantly. Isotope studies using (51)Cr labelled platelets revealed a rapid disappearance of the platelets from the circulation and their trapping in the lung-the primary site of tumour cell lodgement. Dipyridamole and ancrod pretreatment did not influence the decrease of platelets and their accumulation in the lung after tumour cell injection. In contrast, heparin completely prevented the thrombocytopenia and the platelet trapping in the lung. From the present experiments it is concluded that embolic tumour cells lead to early endothelial damage, resulting in local thrombin formation with subsequent irreversible platelet aggregation.
给大鼠静脉注射Walker 256肿瘤细胞后,血小板计数迅速下降,并在随后的观察期内一直维持在低水平。血小板减少与注射的细胞数量密切相关。动脉内注射肿瘤细胞需要相当高的肿瘤细胞数量才能产生类似的血小板减少。无活力的肿瘤细胞和肿瘤细胞碎片也会导致循环血小板出现类似程度的减少。无论是有活力的肿瘤细胞还是肿瘤细胞碎片,在体外均不会使大鼠血小板聚集。注射肿瘤细胞的动物体内存在纤维蛋白单体,提示血管内有纤维蛋白沉积;然而,血浆纤维蛋白原水平并未显著降低。使用(51)Cr标记血小板的同位素研究显示,血小板迅速从循环中消失,并在肺中潴留,肺是肿瘤细胞着床的主要部位。双嘧达莫和抗栓酶预处理对肿瘤细胞注射后血小板的减少及其在肺中的聚集没有影响。相反,肝素完全预防了血小板减少和血小板在肺中的潴留。从目前的实验可以得出结论,栓塞性肿瘤细胞导致早期内皮损伤,从而导致局部凝血酶形成,随后发生不可逆的血小板聚集。