TREATMENT OF FAMILIAL HYPERCHOLESTEROLEMIA BY DEXTRAN SULFATE APHERESIS

家族性高胆固醇血症(FH)患者患 低密度增高导致的早发冠状动脉疾病 脂蛋白(LDL)和脂蛋白(A)胆固醇水平。饮食和药物治疗 可以降低大多数患者的胆固醇浓度 杂合子FH，但有一小部分杂合子和几乎所有 纯合子对治疗没有反应。低密度脂蛋白的选择性去除 对这些患者的硫酸葡聚糖亲和吸附进行了评估 一项合作的多中心美国研究。硫酸葡聚糖分离法 系统(Liposorber LA015 Kanegafuchi，日本)去除低密度脂蛋白和脂蛋白(A) 不影响高密度脂蛋白或白蛋白浓度，从而允许返回 使用自体血浆，无需胶体替代 解决办法。三名纯合子和三名杂合子FH患者 在临床中心登记；全国登记的总队列 其中纯合子10例，杂合子54例。这项研究现在正在进行 完成并关闭，以进一步增加患者，尽管这些 已实现有据可查的益处后，允许继续使用低密度脂蛋白- FDA批准的豁免基础上的分离治疗，等待 设备许可。治疗间隔7~14天。 总胆固醇、低密度脂蛋白和脂蛋白(A)胆固醇水平的平均急剧下降是 在纯合子中分别为70%、81%和68%，在纯合子中为61%、76%和65%， 分别在杂合子中。低密度脂蛋白的时间平均水平 纯合子FH患者胆固醇降低53%(447至310 mg/dL) 杂合子携带者中41%(243~143 mg/dL)。这个 治疗耐受性良好，未见明显不良反应 发生了。 我们的数据表明，硫酸葡聚糖吸附是一种安全和 清除血浆中低密度脂蛋白胆固醇的有效方法，并具有优势， 与简单的血浆交换相比，消除了 胶体替代方案和促进更有益的低密度脂蛋白/高密度脂蛋白 胆固醇比率。 本研究中使用的调查设备的IDE编号为 G880069；IDE持有者是美国卡内卡。

Patients with familial hypercholesterolemia (FH) are at high risk of premature coronary artery disease due to elevated low density lipoprotein (LDL) and 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 homozygotes 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 LA015 Kanegafuchi, Japan) removed LDL and Lp(a) without affecting HDL or albumin concentrations, thus allowing return of autologous plasma and avoiding the need for colloid replacement solutions. Three homozygous and three heterozygous FH patients were enrolled at the Clinical Center; the total cohort enrolled nationwide included 10 homozygotes and 54 heterozygotes. The study is now complete and closed to further accrual of patients, although those having achieved documented benefit are permitted to continue LDL- apheresis treatments on an exemption basis granted by the FDA, pending device licensure. Treatments were administered 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% (447 to 310 mg/dL) in homozygous FH patients and 41% (243 to 143 mg/dL) in heterozygous ones. The treatments were well tolerated and no significant adverse reactions occurred. Our data suggest that dextran sulfate adsorption is a safe and effective way to clear plasma of LDL cholesterol, and has advantages, compared to simple plasma exchange, of eliminating the need for colloid replacement solutions and promoting a more beneficial LDL/HDL cholesterol ratio. The IDE number for the investigational device used in this study is G880069; the IDE holder is Kaneka America.