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越低越好:低密度脂蛋白分离术和半选择性低密度脂蛋白清除疗法后的目标值。

The lower the better: target values after LDL-Apheresis and semi-selective LDL-elimination therapies.

作者信息

Borberg Helmut

机构信息

German Haemapheresis Centre, Deutsches Haemapherese Zentrum, Maarweg 165, Cologne, Germany.

出版信息

Transfus Apher Sci. 2013 Apr;48(2):203-6. doi: 10.1016/j.transci.2013.02.003. Epub 2013 Apr 15.

Abstract

Prior to 1980 the drug therapy of hereditary hypercholesterolaemia was, as compared to nowadays standards, rather limited. There was virtually no effective therapy for homozygous patients, though plasma exchange introduced in France and Britain, demonstrated the use-fullness of the introduction of apheresis techniques. Parallel to the improvement of cholesterol lowering drug therapy for heterozygous patients, apheresis was developed as therapeutic affinity chromatography since 1980 at the university of Cologne for both homozygous and therapy refractory heterozygous patients. This development was named LDL-Apheresis based on the specificity for the removal of Apoprotein B bound cholesterol, the capacity due to the development of a repetitive cycling technique and the economy determined from the reuse of affinity chromatography columns for each single patient. The capacity of the system allowed for the introduction of new standards of post-treatment values such as 100mg/dl total cholesterol or alternatively 50mg/dl LDL-cholesterol and if cholesterol lowering drugs can also applied for a limited extent the rebound can be also slowed down. After 33 years of experience with seven homozygotes and 32 heterozygotes without treatment alternative, we found that in addition to the improvement of the quality of live the extension of live expectancy are the real proof of a therapeutic success as compared to other diagnostic procedures. The average live expectancy of our seven homozygous patients is 45.6 years; our oldest heterozygous patient is 81 years. There are no comparable long term data at present available neither from studies using drugs nor from subsequently developed apheresis techniques which also removed LDL-cholesterol together with plasma constituents not participating in the development of atherosclerosis. Also two homozygous patients giving birth to four children without complication support our concept of aggressive cholesterol lowering therapy being without major side effects (3-4% minor undesired reactions).

摘要

与当今的标准相比,1980年以前遗传性高胆固醇血症的药物治疗相当有限。对于纯合子患者几乎没有有效的治疗方法,尽管法国和英国引入的血浆置换证明了血液分离技术的实用性。在杂合子患者胆固醇降低药物治疗得到改善的同时,自1980年起,科隆大学针对纯合子和治疗难治性杂合子患者,将血液分离发展为治疗性亲和色谱法。由于对去除载脂蛋白B结合胆固醇具有特异性、重复循环技术的发展使其具备处理能力以及亲和色谱柱可重复用于每个患者从而具有经济性,这种发展被命名为低密度脂蛋白血液分离法。该系统的处理能力使得能够引入新的治疗后值标准,如总胆固醇100mg/dl或低密度脂蛋白胆固醇50mg/dl,并且如果在有限程度上也应用胆固醇降低药物,还可以减缓反弹。在对7名纯合子和32名无其他治疗选择的杂合子进行了33年的治疗后,我们发现,与其他诊断程序相比,除了生活质量的改善外,预期寿命的延长是治疗成功的真正证明。我们的7名纯合子患者的平均预期寿命为45.6岁;我们最年长的杂合子患者为81岁。目前,无论是使用药物的研究还是随后开发的也去除低密度脂蛋白胆固醇以及不参与动脉粥样硬化发展的血浆成分的血液分离技术,都没有可比较的长期数据。另外两名纯合子患者顺利产下四个孩子,这也支持了我们积极的胆固醇降低治疗无重大副作用(3 - 4%的轻微不良反应)的观点。

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