TREATMENT OF FAMILIAL HYPERCHOLESTEROLEMIA BY DEXTRAN SULFATE APHERESIS

家族性高胆固醇血症(FH)IIa型患者高危 因低密度升高而导致的早发冠状动脉疾病 脂蛋白(LDL)和脂蛋白a[Lp(A)]胆固醇水平。饮食和 药物治疗可以降低大多数高血压患者的胆固醇浓度 杂合子FH，但有一小部分杂合子和几乎所有 纯合子患者对治疗没有反应。选择性去除低密度脂蛋白 通过葡聚糖硫酸盐亲和吸附评估这些患者在 一项合作的多中心美国研究。硫酸葡聚糖分离法 系统(Liposorber LA-15，Kaneka，日本)去除低密度脂蛋白和Lp(A)而无需 降低白蛋白水平，从而允许自体血浆在没有 需要胶体替代解决方案。此外，高密度 脂蛋白(HDL)，一种具有高度保护作用的脂质部分 心血管疾病，随着时间的推移而增加。三个纯合子和三个 杂合子FH患者在临床中心登记； 在全国范围内纳入的队列包括10个纯合子和54个杂合子。 每隔7至14天进行一次治疗。平均急性 总胆固醇、低密度脂蛋白和脂蛋白(A)胆固醇水平分别降低了70%、81%和 在纯合子中分别为68%和61%，在 杂合子。时间平均水平的低密度脂蛋白胆固醇降低了53% (447至310 mg/dl)和41%(243至143) Mg/dl)。这些治疗耐受性很好。 使用血管紧张素转换酶(ACE) 注意到抑制剂和潮红和低血压的发展，以及 血管紧张素转换酶抑制剂治疗现在通常至少中断24小时 在每一次手术之前。多中心研究的结果表明， 硫酸葡聚糖吸附是一种安全有效的血浆净化方法 低密度脂蛋白，并具有与单纯血浆相比的优势 交换，消除了对胶体替换溶液的需要，并 提高高密度脂蛋白水平。 在这项研究中收集的数据被用作许可的基础 LA-15系统，它被FDA批准用于治疗FH 1996年7月。患者现在继续进行长期的低密度脂蛋白- 分离登记处“，以收集许可证后的数据，长期- 原发性和继发性动脉粥样硬化发展的长期治疗 事件，以及总体生存。

Patients with familial hypercholesterolemia (FH) type IIa are at high risk of premature coronary artery disease due to elevated low-density lipoprotein (LDL) and lipoprotein a [Lp(a)] cholesterol levels. Diet and drug therapy can reduce cholesterol concentrations in most patients with heterozygous FH, but a small proportion of heterozygous and nearly all homozygotus patients do not respond to therapy. Selective removal of LDL by dextran sulfate affinity adsorption was evaluated in these patients in a collaborative multicenter U.S. study. The dextran sulfate apheresis system (Liposorber LA-15, Kaneka, Japan) removed LDL and Lp(a) without lowering albumin levels, thus allowing return of autologous plasma without the need for colloid replacement solutions. Furthermore, high-density lipoprotein (HDL), a lipid moiety with highly protective effects against cardiovascular disease, increased over time. Three homozygous and three heterozygous FH patients were enrolled at the Clinical Center; the total cohort enrolled nationwide included 10 homozygotes and 54 heterozygotes. Treatments were administered at 7- to 14-day intervals. Mean acute reductions in total, LDL, and Lp(a) cholesterol levels were 70%, 81%, and 68%, respectively, in homozygotes and 61%, 76%, and 65%, respectively, in heterozygotes. Time-averaged levels of LDL cholesterol were reduced 53% (from 447 to 310 mg/dl) in homozygous FH patients and 41% (from 243 to 143 mg/dl) in heterozygous patients. The treatments were very well tolerated. An adverse association between using angiotensin converting enzyme (ACE) inhibitors and the development of flushing and hypotension was noted, and ACE inhibitor therapy is now routinely discontinued for at least 24 hours prior to each procedure. The results of the multicenter study suggest that dextran sulfate adsorption is a safe and effective way to clear plasma of LDL cholesterol, and has the advantages, compared with simple plasma exchange, of eliminating the need for colloid replacement solutions and increasing HDL levels. The data gathered in this study were used as the basis for licensure of the LA- 15 system, which was approved by the FDA for treatment of FH in July 1996. Patients are now continuing long-term follow-up on an "LDL- Apheresis Registry" to gather post-licensure data on the effect of long- term treatment on the development of primary and secondary atherosclerotic events, and on overall survival.