低分子量肝素和地塞米松对PNH患者红细胞体外抑制溶血作用的研究

目的 研究低分子量肝素和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作用。方法 采集6例典型溶血发作的PNH患者外周血，采用Ham试验、微量补体溶血敏感试验（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对溶血的影响；同时检测各种不同剂量的药物对活化部分凝血活酶时间（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。同时，在此种剂量下APTT的延长未超过2倍。（2）Ham试验检测时地塞米松有抑制溶血的作用，mCLST检测时地塞米松随加入方法的不同对溶血的作用不同。低分子量肝素在Ham和mCLST试验中均可发挥抑制溶血的作用。结论 低分子量肝素、地塞米松均有抑制PNH患者红细胞溶血的作用，其作用机制存在差异；二者具有协同作用，治疗剂量对出凝血的影响较小，在PNH患者红细胞溶血发作的治疗中有应用前景。

In vitro effects of low-molecular weight heparin and dexamethasone on the hemolysis of red blood cells from paroxysmal nocturnal hemoglobinuria patients

OBJECTIVE: To study the in vitro effects of low-molecular weight heparin (LMWH) and dexamethasone on the hemolysis of red blood cells from paroxysmal nocturnal hemoglobinuria (PNH) patients. METHODS: By Ham's test and micro-complement lysis sensitive test (mCLST), the changes of hemolysis of red blood cells from 6 PNH patients were tested by adding different doses of LMWH and dexamethasone into the test mixture. The effects of LMWH and dexamethasone on the coagulation of the tested blood samples were also studied by activated partial thromboplastin time (APTT). RESULTS: (1) Either LMWH or dexamethasone could dose-dependently inhibit the hemolysis of PNH red blood cells, and the effects were synergistic when added together. The same dose of LMWH induced a less than 100% prolongation of APTT. (2) Dexamethasone could inhibit the hemolysis in Ham's test and had different effects on the hemolysis by different adding methods in mCLST. LMWH could inhibit the hemolysis in both Ham's test and mCLST. CONCLUSION: Both LMWH and dexamethasone could inhibit the hemolysis of PNH red cells and showed a synergistic effect. The mechanisms of the inhibition of hemolysis were different. Furthermore, a tolerable dose of LMWH induced only a limited prolongation of APTT, which might be useful for controlling acute hemolysis and reducing the dose of dexamethasone.