Uauy R, Zwiener R J, Phillips M J, Petruska M L, Bilheimer D W
Department of Pediatrics, University of Texas Southwestern Medical Center, Dallas 75235-9063.
J Pediatr. 1992 Jun;120(6):892-8. doi: 10.1016/s0022-3476(05)81956-0.
We evaluated the safety and efficacy of dextran sulfate low-density lipoprotein (LDL) apheresis in the treatment of three children (aged 6, 7, and 10 years) with severe familial homozygous hypercholesterolemia and undetectable LDL receptor activity. A total of 35 double plasma volume procedures were performed. The ranges of the mean decreases of the three patients in plasma lipid concentrations after LDL apheresis (p less than 0.0001) were as follows: total cholesterol, 76% to 79%; LDL-cholesterol, 78% to 81%; very low density lipoprotein cholesterol, 69% to 75%; high-density lipoprotein cholesterol, 27% to 40%; and triglycerides, 34% to 68%. There were statistically significant but clinically and biologically irrelevant changes in hematologic indexes, serum chemistry values, immunoglobulin levels, complement activity, and plasma concentrations of fat-soluble vitamins. Simple correlation analysis of the variables affecting total cholesterol removal showed significant correlation coefficients (r values) for preapheresis total cholesterol values (r = 0.70; p less than 0.01) and preapheresis LDL-cholesterol values (r = 0.61; p less than 0.01). A multiple regression model explained 82% of the variance based on the preapheresis cholesterol concentration, volume of whole blood processed, and the serum albumin concentration. Side effects of the LDL-apheresis treatments were rare and included abdominal cramping and urticaria. Two procedures were aborted because of intravenous access problems in the younger children. This study confirms that LDL apheresis using a dextran sulfate affinity column is efficacious in rapidly lowering total and LDL-cholesterol concentrations. Furthermore, the procedure is safe and well tolerated by children as young as 6 years of age. This treatment may prevent the progression of atherosclerosis in children with homozygous familial hypercholesterolemia and may therefore avert early death.
我们评估了硫酸葡聚糖低密度脂蛋白（LDL）单采术治疗三名患有严重家族性纯合子高胆固醇血症且低密度脂蛋白受体活性检测不到的儿童（年龄分别为6岁、7岁和10岁）的安全性和有效性。总共进行了35次双倍血浆容量程序。LDL单采术后三名患者血浆脂质浓度的平均降低范围如下（p<0.0001）：总胆固醇，76%至79%；LDL胆固醇，78%至81%；极低密度脂蛋白胆固醇，69%至75%；高密度脂蛋白胆固醇，27%至40%；甘油三酯，34%至68%。血液学指标、血清化学值、免疫球蛋白水平、补体活性和脂溶性维生素血浆浓度有统计学上显著但临床和生物学上无关紧要的变化。对影响总胆固醇清除的变量进行简单相关分析显示，采前总胆固醇值（r = 0.70；p<0.01）和采前LDL胆固醇值（r = 0.61；p<0.01）的相关系数（r值）显著。多元回归模型基于采前胆固醇浓度、处理的全血体积和血清白蛋白浓度解释了82%的方差。LDL单采术治疗的副作用很少，包括腹部绞痛和荨麻疹。由于年幼儿童静脉通路问题，有两次程序中止。本研究证实，使用硫酸葡聚糖亲和柱的LDL单采术能有效快速降低总胆固醇和LDL胆固醇浓度。此外，该程序安全，6岁的儿童也能很好耐受。这种治疗可能预防纯合子家族性高胆固醇血症儿童动脉粥样硬化的进展，因此可能避免过早死亡。
