ERYTHROCYTES WITH COVALENTLY BOUND FIBRINOGEN AS A CELLULAR REPLACEMENT FOR THE TREATMENT OF THROMBOCYTOPENIA
ERYTHROCYTES WITH COVALENTLY BOUND FIBRINOGEN AS A CELLULAR REPLACEMENT FOR THE TREATMENT OF THROMBOCYTOPENIA
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DOI：
10.1111/j.1365-2362.1992.tb01943.x
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发表时间：
1992-02-01
影响因子：
5.5
通讯作者：
LIVNE, AA
中科院分区：
文献类型：
--
作者：
AGAM, G;LIVNE, AA
血小板减少症，特别是自身免疫性血小板减少症，是一种高患病率的疾病，治疗方案不令人满意。本研究旨在探索替代治疗的可行性，其依据是经修饰以携带共价结合的纤维蛋白原的自体红细胞将被动参与剩余血小板的聚集，从而增加止血需求，同时抵抗针对血小板的自身免疫反应。对纤维蛋白原与红细胞（RBC）交联的几种方法进行了测试。甲醛（33 μ M）在23 ℃下作用10分钟，每个红细胞附着58个纤维蛋白原分子。这些红细胞与未处理的红细胞在以下性质上无法区分：渗透脆性、结合血红蛋白、沉降率、乙酰胆碱酯酶活性、巨噬细胞的吞噬作用、与K562细胞的玫瑰花结形成。结果表明，与纤维蛋白原交联的RBC能够参与血小板的体外聚集，并且在自身免疫性血小板减少症动物模型中的体内止血过程中确实有效。
Thrombocytopenia in general, and autoimmune thrombocytopenia in particular, is a disease of high prevalence with a non-satisfactory regime of treatment. The present study aimed to explore the feasibility of an alternative treatment, based on the rationale that autologous erythrocytes modified to bear covalently bound fibrinogen would participate passively in the aggregation of the remaining platelets, thus augmenting the haemostatic needs, while resisting the autoimmune reaction directed towards the platelets. Several procedures for the cross-linking of fibrinogen to red blood cells (RBCs) were tested. Formaldehyde (33-mu-M) for 10 min at 23-degrees-C attached 58 fibrinogen molecules per erythrocyte. These erythrocytes were indistinguishable from untreated erythrocytes in the following properties: osmotic fragility, bound haemoglobin, sedimentation rate, acetylcholinesterase activity, phagocytosis by macrophages, rosette formation with K562 cells. It is shown that RBCs cross-linked with fibrinogen are capable of participating in the in vitro aggregation of platelets and are indeed effective in the in vivo process of arrest of bleeding in an animal model of autoimmune thrombocytopenia.