低分子量肝素和肾上腺糖皮质激素对阵发性睡眠性血红蛋白尿症患者红细胞体外溶血抑制作用的研究(英文)

Inhibiting effects of low-molecular weight heparin and adrenocortical hormone on hemolysis of red cells in patients with paroxysmal nocturnal hemoglobinuria in vitro

目的 研究低分子量肝素和肾上腺糖皮质激素 (地塞米松 )对阵发性睡眠性血红蛋白尿症 (PNH)患者红细胞体外溶血的抑制作用。方法 采集 6例典型溶血发作的PNH患者的外周血 ,采用酸溶血实验 (Ham’s实验 )、微量补体溶血敏感实验(mCLST) ,检测单独或联合加入不同剂量的低分子量肝素和地塞米松后溶血的变化情况 ;同时检测对激活部分凝血活酶时间 (APTT)的影响。结果 ①低分子量肝素、地塞米松体外对PNH患者的红细胞均有抑制溶血的作用 ,此种作用随剂量的增大而增大。当同时加入上述两种治疗量的药物时 ,对溶血的抑制作用明显加强 ,提示低分子量肝素的应用可减少地塞米松的用量。同时 ,在此种剂量下APTT的延长未超过 2倍 ;②采用mCLST检测时发现地塞米松通过抑制抗体与红细胞上抗原的结合 ,从而抑制补体的活化而产生抑制溶血的作用 ,而对补体的活化过程并无明显抑制作用 ;采用Ham’s实验检测时发现地塞米松还可能通过阻断补体C3活化前的启动环节而抑制溶血。低分子量肝素在Ham’s和mCLST实验中均可发挥抑制溶血的作用 ,说明它阻断了补体活化中的某个环节而抑制溶血。结论 低分子量肝素、肾上腺糖皮质激素均有抑制PNH患者红细胞溶血的作用 ,其作用机制不同 ;二者对溶血抑制具有协同作用 。

OBJECTIVE: To study the effects of low-molecular weight heparin (LMWH) and adrenocortical hormone (dexamethasone) on the hemolysis of red cells of patients with paroxysmal nocturnal hemoglobinuria (PNH) in vitro. METHODS: Using Ham's test and micro-complement lysis sensitive test (mCLST), the changes in hemolysis of red cells from 6 typical PNH cases were examined after adding LMWH and dexamethasone in different concentrations into the test solution in vitro. The effects of LMWH and dexamethasone on the coagulation of the tested blood samples were also studied using the activated partial thromboplastin time (APTT) test. RESULTS: Both LMWH and dexamethasone inhibited the hemolysis of PNH red cells, and they also showed a synergistic effect. The inhibiting effects were dose-dependent. Moreover, a tolerable dose of LMWH induced a limited prolongation of APTT. Dexamethasone showed two possible mechanisms in the inhibition of PNH red cells hemolysis through Ham's test and mCLST, respectively: (1) inhibiting both antibodies binding to red cells and (2) the initiation of the activation of complement 3 (C3). LMWH could inhibit hemolysis as determined by both Ham's test and mCLST, which indicated that LMWH could block the activation of complement cascade. CONCLUSIONS: Both LMWH and dexamethasone could inhibit hemolysis in PNH, and they showed a synergistic effect. Their mechanisms of inhibiting hemolysis differed from each other. Furthermore, a tolerable dose of LMWH induced a limited prolongation of APTT. LMWH might be useful for controlling acute hemolysis in patients with PNH and reducing the dose of adrenocortical hormone.