IMMUNE ENDOTHELIAL-CELL INJURY IN HEPARIN-ASSOCIATED THROMBOCYTOPENIA
IMMUNE ENDOTHELIAL-CELL INJURY IN HEPARIN-ASSOCIATED THROMBOCYTOPENIA
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DOI：
10.1056/nejm198703053161004
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发表时间：
1987-03-05
影响因子：
158.5
通讯作者：
TANNENBAUM, S
中科院分区：
文献类型：
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作者：
CINES, DB;TOMASKI, A;TANNENBAUM, S
我们研究了对内皮细胞的免疫损伤可能在一些肝素相关性血小板减少患者血栓形成的发生中起作用的可能性。有此临床诊断的27例患者的血清样本均含有肝素依赖的血小板抗体，并在内皮细胞上沉积了比正常数量更多的免疫球蛋白、免疫球蛋白A或免疫球蛋白M，刺激组织因子的产生。在停用肝素后对患者进行研究时，不再检测到免疫球蛋白与内皮细胞的结合，但在临床复发的患者再次接触肝素后的几天内，免疫球蛋白与内皮细胞的结合重新出现。免疫球蛋白与内皮细胞的结合可通过用肝素或肝素硫酸盐结合到Sepharose上的血清样品预吸附或通过酶裂解细胞结合的肝素硫酸盐而部分减少，而加入肝素硫酸盐可增强免疫球蛋白与内皮细胞的结合。因此，一些肝素相关性血小板减少患者的血清可能含有与内皮细胞结合的肝素或内皮细胞合成的硫酸肝素反应的抗体。对血小板和内皮细胞的免疫损伤可能在某些患者肝素治疗后血栓形成的发生中起作用。
We studied the possibility that immune injury to endothelial cells may have a role in the development of thrombosis in some patients with heparin-associated thrombocytopenia. Serum samples from each of 27 patients who had this clinical diagnosis contained heparin-dependent platelet antibodies and deposited more than normal amounts of IgG, IgA, or IgM on endothelial cells, stimulating the production of tissue factor. Binding of immunoglobulins to endothelial cells was no longer detected when the patients were studied after heparin was withdrawn, but reappeared within several days upon reexposure to heparin in a patient who experienced a clinical recurrence. Binding of immunoglobulin to endothelial cells was partially reduced by the preadsorption of serum samples with heparin or heparan sulfate bound to Sepharose or by enzymatic cleavage of cell-bound heparan sulfate, and was augmented by the addition of heparan sulfate. Thus, serum from some patients with heparin-associated thrombocytopenia may contain antibodies that react with heparin bound to endothelial cells or with heparan sulfate synthesized by endothelial cells. Immune injury to both platelets and endothelial cells may play a part in the development of thrombosis in some patients after heparin therapy.