Successful treatment of homozygous familial hypercholesterolemia using cascade filtration plasmapheresis.

"DISCUSSION: Elevated LDL-C causes angina pectoris, MI, and suddendeath during the second decade of life in homozygous FHpatients. Several studies have shown that long-term LDLapheresisfor homozygous FH patients prevents coronaryheart disease [1,14]. De Gennes first reported the effectivenessof plasma exchange in successfully reducing plasmacholesterol levels in 1967; it was well tolerated, but repetitionof the procedure was emotionally difficult for thepatients (15). In 1976 Lupien performed plasmapheresisto selectively remove LDL-C; subsequently, LDL apheresisreplaced plasma-exchange therapy [16]. The newprocedure was feasible, well tolerated, and had a greatereffect on clinical status. Recently, several new apheresistechniques were developed, including dextran sulphatecelluloseadsorption (DSA), the heparin extracorporealLDL precipitation system (HELLP), direct adsorption oflipoprotein using hemoperfusion (DALI), immunoadsorption,and cascade filtration [17,18,19,20]. Researchers reportedthat these technically different procedures were similarlyeffective in lowering serum LDL-C [21,22,23]. : The American Society for Apheresis (ASFA) recommendscascade filtration plasmapheresis as a standard andacceptable primary treatment modality for FH (category1) [24]. With the cascade filtration system atherogenic lipoproteinsare eliminated from plasma, according to theirmolecular size. The cascade filter pore diameter is >15-30nm, which ensures that larger plasma proteins (lipoproteins,albumin, fibrinogen, etc.) are caught in the filter, allowingsmaller molecules to pass through [25]. In the presentstudy LDL-C levels significantly decreased; mean acutereduction in LDL-C was 70.8%, and reductions in other lipoproteinswere as follows: total cholesterol: 57.9%; HDLC:40.7%; triglycerides: 59.2%. The Coker [12] study reporteda reduction of 63% in mean plasma LDL-C usingthe cascade filtration technique in 10 patients. Zwiener[6] obtained a 71% reduction in mean plasma LDL-C usingthe DSA technique in 2 patients. In the Bosh study[4] acute mean reductions in lipoproteins achieved by theDALI system were as follows: LDL-C: 69%; triglycerides:27%; HDL-C: 11%; total cholesterol: 52%. Another studyperformed using the cascade filtration system reported thefollowing acute mean reductions: LDL: 61.6%; total cholesterol:59.5%; HDL-C: 31.1%; triglycerides: 48.1% [26]. : Studies have shown that cascade filtration can causeundesirable reductions in other large-molecule proteins,such as immunoglobulins, serum total protein, albumin,and fibrinogen, but these levels remained within normalranges and were clinically unimportant. In the presentstudy the mean decrease in IgG was 30.9% and was withinthe normal range for the patients’ age group. Mean decreasein IgG ranged from 27% to 32% in other studies [25,27].Although acute mean reductions of 59.7% in fibrinogen,21.5% in serum protein, 14.7% in serum albumin, and14.2% in platelets were noted, we did not observe any infection,hemorrhagia, or edema in our patients. In a studyperformed using the DALI system acute mean reductionsof 15% in fibrinogen, 6% in platelets, and 8% in serumalbumin were reported [4]. Another study performed usingthe cascade filtration system reported mean reductionsof 49.9% in fibrinogen, 19.6% in albumin, and 26.9% inserum total protein [26]. : Undesirable side effects rarely occur in patients treatedwith the cascade filtration method. In the REMUKASTstudy adverse reactions were reported in 34 of 1,702 treatments(2%), including hypotension (41%), nausea (18%),and edema (17%) [28]. Another study reported the followingclinical side effects: hypotension (0.2%), chills (0.1%),and nausea and vomiting (0.2%) [12]. We observed similarside effects in the present study (hypotension, chills, nausea and vomiting, etc.) and their frequency was nothigher than expected. : In conclusion, the cascade filtration technique is a very effective treatment for removing undesirable lipoproteins, such as LDL-C, total cholesterol, and triglycerides, from plasma; it is safe, and is associated with minor adverse effects and negligible technical problems. : Conflict of Interest Statement : The authors of this paper have no conflicts of interest, including specific financial interests, relationships, and/ or affiliations relevant to the subject matter or materials included."