Low–Density Lipoprotein Apheresis in the Treatment of Two Patients with Coronary Heart Disease and Extremely Elevated Lipoprotein (a) Levels

Abstract: Hyperlipidemia and elevated lipoprotein (a) (Lp[a]) levels have been linked to the development and progression of premature atherosclerosis. Our study concerned 2 white male patients (aged 36 and 42 years) with heterozygous familial hypercholesterolemia and extremely elevated Lp(a) concentrations that were resistant to diet regimens and lipid–lowering drugs. The patients were treated with low–density lipoprotein (LDL) apheresis for 59 months (Liposorber system, Kaneka, Japan) and 19 months (immunoadsorption system, special Lp(a) columns; Lipopak; Pocard, Russia), respectively. The concentration of Lp(a) decreased on average by 50%, total cholesterol by 27%, LDL cholesterol by 41%, triglycerides by 43%, and fibrinogen by 16%. High–density lipoprotein (HDL) cholesterol increased by approximately 4%. Before treatment with LDL apheresis, each patient had suffered 3 myocardial infarctions, and had had 4 and 6 coronary angiographies with 2 and 4 percutaneous transluminal angioplasties (PTCAs), respectively. Since treatment with LDL apheresis, no myocardial infarctions or cardiac complaints were observed. In the course of treatment, both patients reported an increased performance. Available data suggest that LDL apheresis may be effective in the treatment of patients, the only risk factor for premature atherosclerosis being extremely elevated Lp(a) concentrations.     

Treatment of Severe Hyperlipidemia: Six Years' Experience with Low–Density Lipoprotein Apheresis

Abstract: In total, 30 patients suffering from familial hypercholesterolemia, resistant to diet and lipid–lowering drugs, were treated for up to 6 years (3.6 ± 1.6; range, 0.2–6.8 years) with low–density lipoprotein (LDL) apheresis. Three different systems were used; the dextran sulfate adsorption system (Kaneka) for 27 of 30 patients, the immunoadsorption system from Baxter for 2 of 30 patients, and the immunoadsorption system with special li–poprotein(a) (Lp[a]) columns from Lipopak for one patient. Prior to the LDL apheresis, 23 of 30 patients suffered from coronary heart disease. Twenty of 23 patients suffered intermittently from symptoms of angina, excertional dyspnea, and claudication. With LDL apheresis, reductions of 47% for total cholesterol, 49% for LDL, 26% for Lp(a), and 40% for triglycerides were reached. Severe side effects such as shock or allergic reactions were very rare (0.55%). In the course of treatment with LDL apheresis, an improvement in general well–being and increased performance were experienced in 27 of 30 patients. A reduction of nitrate medication between 60 and 100% was observed in 17 of 23 patients. The present data clearly demonstrate that treatment with LDL apheresis in patients suffering from severe familial hyperlipidemia, resistant to maximum conservative therapy, is very effective and safe even over long periods of time.     

Treatment of Homozygous Familial Hypercholesterolemia with Low Density Lipoprotein Apheresis: A 4 Year Follow-Up Study

Abstract: Hypercholesterolemia and elevated lipoprotein (a) (Lp[a]) levels are considered to be risk factors for the development and progression of premature atherosclerosis. The purpose of our report is to describe the effects of low density lipoprotein (LDL) apheresis (Liposorber system, Kanegafuchi Chemical Industrial Company LTD, Osaka, Japan) on serum lipoprotein concentrations and the clinical status in 2 male patients with homozygous familial hypercholesterolemia. Compared with pretreatment values, the posttreatment concentrations of total cholesterol, LDL cholesterol, and Lp(a) were significantly reduced by 50–60% (p < 0.0001). The concentration of high density lipoprotein (HDL) cholesterol was slightly affected. After one treatment session, LDL cholesterol and Lp(a) were decreased on average by 65% and then increased to reach about 70–75% of the pretreatment values before the next session. Prior to the treatment with LDL apheresis, each patient had suffered one myocardial infarction and had had 2 coronary angiographies. After treatment with LDL apheresis, neither cardiac complaints nor myocardial infarction were observed. The xanthomas were much decreased during the treatment or disappeared. We conclude that LDL apheresis can be continued safely and without major technical problems for several years. Apheresis effectively lowers the serum levels of total and LDL cholesterol. Furthermore, it reduces Lp(a), which is not influenced by lipid-lowering drugs. The reduction of LDL cholesterol and Lp(a) may delay the progression of the atherosclerotic process, thereby helping to reduce the risk of new episodes of coronary heart disease and thus extending the life expectancy in these patients.     

Extracorporeal Removal of Lipids by Dextran Sulfate Cellulose Adsorption

Abstract: Extracorporeal removal of low–density lipoprotein (LDL) cholesterol by dextran sulfate adsorption is indicated in patients with diet and drug resistant hypercholesterolemia to prevent or to regress coronary heart disease. Plasma separation is the first step in the process, followed by adsorption of LDL cholesterol and lipoprotein (a) (Lp[aJ) to negatively charged dextran sulfate co–valently bound to cellulose beads. The reduction per treatment in LDL cholesterol is 65–75% and in Lp(a) 40–60%. In most patients one treatment per week is sufficient to reduce mean LDL to 100–150 mg/dl. Minor side effects occur in 2–6% of treatments. Major side effects are rare. In uncontrolled studies long–term treatment was associated with inhibition of progression and induction of regression of coronary artery disease. LDL apheresis by dextran sulfate may increase blood perfusion of some tissues, and preliminary results indicate a beneficial effect on therapy resistant nephrotic syndrome with hypercholesterolemia.     

LDL Apheresis in a Homozygous Familial Hypercholesterolemic Child Aged 4.5

Abstract: Preliminary experience with the efficacy and safety of dextran sulfate cellulose low-density lipoprotein (LDL) apheresis for the treatment of a 4.5-year-old girl with homozygous familial hypercholesterolemia and coronary artery disease is reported. The decrease of the most atherogenic apolipoprotein B-containing lipoproteins, low-density lipoprotein (LDL) and lipoprotein(a) (Lp [a]), were in the ranges of 63.1–68.7%, and 52.5–58.6%, respectively. The child tolerated LDL apheresis without any clinically significant complications. Therefore, she was submitted to a long-term program of treatment at intervals of 15 days. The experience suggests the possibility of an early beginning of extracorporeal treatment with LDL apheresis in children severely affected by homozygous or double heterozygous familial hypercholesterolemia.     

Efficacy and safety of a new whole-blood low-density lipoprotein apheresis system (Liposorber D) in severe hypercholesterolemia

Low-density lipoprotein (LDL) apheresis is an extracorporeal modality to lower LDL cholesterol. While most of the devices eliminate LDL particles from plasma, a recently introduced whole-blood perfusion column (DALI) adsorbs lipoproteins directly from whole blood. We investigated the efficacy and safety of a new whole-blood LDL apheresis system (Liposorber D) in 10 patients with severe hypercholesterolemia in a multicenter trial. In 93 LDL aphereses, the mean reduction in LDL cholesterol and lipoprotein(a) was 62.2 +/- 11.5% and 55.6 +/- 16.9%, respectively (P < 0.01). If hemodilution during apheresis was considered, the reductions were 58.0 +/- 10.9 and 55.3 +/- 10.9%, respectively (P < 0.01), while high-density lipoprotein (HDL) cholesterol did not change significantly. Three mild episodes of hypocalcemia and two mild episodes of arterial hypotension were observed; however, LDL apheresis could be continued in each case. In conclusion, the new whole-blood LDL apheresis with Liposorber D is a safe, simple, and useful modality to reduce LDL cholesterol and lipoprotein(a) in cardiovascular high-risk patients.     

Low–Density Lipoprotein Apheresis Versus Lipid Lowering Drugs in the Treatment of Severe Hypercholesterolemia: Four Years' Experience

Abstract: Elevated lipoprotein concentrations seem to be linked strongly in a dose dependent manner to an increased incidence of atherosclerosis. A total of 47 patients suffering from severe hyperlipidemia were matched to treatment with LDL apheresis (Baxter, Kaneka, Li–popak; 24 patients, aged 50.2 ±11.5 years), diet, and/or lipid–lowering drugs or with diet and lipid–lowering drugs only (23 patients, aged 48.8 ±11.8 years). After treatment periods of 49.8 ±13.4 months (apheresis group, 2,396 treatment sessions) and 38.6 ± 15.1 months (drug group), the ensuing results revealed significant differences (p <0.0001): –47.3% versus –12.1% for total cholesterol, –46.9% versus –21.8% for LDL, +8.4% versus +0.9% for HDL, –52.0% versus – 13.1% for the LDL/HDL ratio, –36.4% versus –16.2% for triglycerides, and –25.9% versus + 1.5% for lipoprotein (a). In the apheresis group, one patient died of myocardial infarction; in the drug group, there was one nonfatal myocardial infarction and the manifestation of coronary heart disease in 3 cases. There were no severe side effects in either group. All patients in the apheresis group responded to therapy. The present trial suggests that a continuing reduction in serum lipid concentrations may lower, in a dose dependent manner, the risk for development and progression of coronary heart disease. Regarding clinical and laboratory results, LDL apheresis seems to be safe, effective therapy for treatment of severe hyperlipidemia.     

LDL Apheresis: A Novel Technique (LIPOCOLLECT 200)

Therapeutic means to lower Lp(a) are limited. The most effective method to reduce plasma Lp(a) concentration significantly is therapeutic apheresis, namely, low‐density lipoprotein (LDL) lipoprotein(a) (Lp(a)) apheresis. A novel technique based on reusable LDL adsorber called Lipocollect 200 (Medicollect, Rimbach, Germany) allows the removal of both LDL and Lp(a) from plasma. Two male patients with hyperLp(a)lipoproteinemia and angiographically established progressive coronary heart disease, without rough elevation of LDL‐cholesterol, who did not respond to diet and medication were submitted to 50 LDL Lp(a) aphereses with Lipocollect 200 LDL Lp(a)‐adsorber at weekly and biweekly intervals. Total cholesterol and LDL cholesterol plasma levels fell significantly by 48.3% (±6.7) to 61.6% (±12.7) (first patient), and 42.5% (±6.3) to 60.6% (±14.3) (second patient), respectively (all differences: P ≤ 0.001). High‐density lipoprotein (HDL)‐cholesterol concentration in plasma did not show statistically significant change. Plasma triglycerides were also significantly reduced by 43.6% (±24.4) (first patient) and 42.3% (±13) (second patient) (both differences: P ≤ 0.001). Plasma Lp(a) showed a statistically significant percent reduction in plasma as expected: 64.7 ± 9.5 (first patient), and 59.1 ± 6.7 (second patient) (both differences: P ≤ 0.001). Plasma fibrinogen concentration was decreased by 35.9% (±18.7) (P ≤ 0.05) (first patient) and 41.8% (±11.5) (second patient) (P ≤ 0.005). Considering the reduction rate between the first and the last procedures, we have compared the mean percent reduction of the first five treatments (from session #1 to #5) with the last five treatments (from session #21 to #25). We have observed an increasing reduction of all activity parameters on both patients apart from HDL‐cholesterol (first patient) and triglyceride (second patient) that showed a decreasing reduction rate. Both patients followed the prescribed schedule and completed the study. Clinically, all sessions were well tolerated and undesired reactions were not reported. The Lipocollect 200 adsorber proved to have a good biocompatibility. In this study, the adsorber reusability for several sessions was confirmed.     

Short–and Long–Term Effects on Serum Lipoproteins by Three Different Techniques of Apheresis

Abstract: Low–density lipoprotein (LDL) apheresis is applied in patients with coronary heart disease because of severe inherited forms of hypercholesterolemia, for which dietary and combined drug treatment cannot lower LDL cholesterol concentrations less than 130 mg/dl. The following article describes the changes in lipoprotein levels in a total of 19 patients undergoing weekly LDL apheresis. Immunoadsorption, operating with polyclonal antibodies against apolipoprotein B–100, was used in 6 patients. Five patients were put on heparin–induced extracorporeal LDL precipitation (HELP) therapy; 6 received dextran sulfate adsorption treatments. Under steady–state conditions a single treatment reduced LDL cholesterol by 149 ± 3 m/dl with immunoadsorption, 122 ± 2 mg/dl with HELP, and 124 ± 18 mg/dl with dextran sulfate adsorption. Lipoprotein (a) (Lp[a]) declined by 52 to 65%. Very low density lipoprotein (VLDL) cholesterol and VLDL triglycerides declined by 45 to 55% because of the activation of lipoprotein lipase and precipitation during the HELP procedure. In all procedures, there was a small reduction in the different high–density lipoprotein fractions, which had returned to normal after 24 h. The long–term HDL3 cholesterol levels increased significantly. During all procedures there was a decrease in the molar esterification rate of lecithin cholesterol acyltrans–ferase activity. All changes in lipid fractions were paralleled by changes in the corresponding apolipoprotein levels. It is concluded that all three techniques described are powerful tools capable of lowering LDL cholesterol in severe hereditary forms of hypercholesterolemia. In HELP and dextran sulfate adsorption, the amount of plasma is limited by the elimination of other plasma constituents. Immunoadsorption may thus be preferred in very severe forms of hypercholesterolemia.     

Low–Density Lipoprotein Removal Methods by Membranes and Future Perspectives

Abstract: Since the application by Thompson et al. in 1975 of plasma exchange for the treatment of 2 patients with familial hyperlipidemia, plasma purification techniques for selective low–density lipoprotein (LDL) removal (i.e., LDL apheresis) have been developed and adopted for the management of this disease. Thermofil–tration is one of the LDL apheresis systems that utilizes membrane techniques developed by Nose and Malchesky's group in 1985. This article reviews its rationale, in vitro studies, animal studies, and clinical investigation. Thermofiltration effectively and selectively removes LDL cholesterol while retaining in the plasma physiologically important macromolecules such as albumin and high–density lipoprotein (HDL) cholesterol. Based on the global view of the treatment of atherosclerosis by LDL apheresis, membrane techniques are as effective, safe, and simpler to apply than other methods. Additionally, these methods are effective for the removal of lipoprotein (a) and fibrinogen; thus, they can address the needs in these application areas.     

Does Regular Lipid Apheresis in Patients With Isolated Elevated Lipoprotein(a) Levels Reduce the Incidence of Cardiovascular Events?

Elevated lipoprotein(a) (Lp(a)) is known as an independent risk factor for atherosclerosis and cardiovascular events. Regular lipid apheresis decreases elevated Lp(a) concentrations. However, there is a lack of reliable data regarding the effect of lipid apheresis on cardiovascular endpoints. To assess the effects of apheresis, we compared the occurrence of cardiovascular events in 37 patients treated regularly with lipid apheresis at the time periods of preinitiation of apheresis and during apheresis treatment. A retrospective analysis of 37 patients (35 men and two women; aged 58 years ± 11 [mean ± standard deviation]; body mass index 26 kg/m² ± 3; low‐density lipoprotein (LDL)‐cholesterol before apheresis 84 mg/dL ± 21; Lp(a) before apheresis 112 mg/dL ± 34) treated regularly with lipid apheresis was performed. Patients' medical records were screened for cardiovascular events at the preapheresis and during apheresis periods. Apheresis led to a significant reduction of lipid levels (LDL cholesterol ?60%; Lp(a) –68%) measured after apheresis. The event‐free survival rate after 1 year in the preapheresis period was 38% (22–54%, 95% confidence interval [CI]) vs. 75% (61–89%, 95% CI) in the during‐apheresis period with a statistically significant difference (P < 0.0001). Apheresis seems to lower the progression of atherosclerosis leading to a reduced number of cardiovascular events in hyperlipoproteinemia(a). Because prospective and controlled trials are lacking, the therapeutic effectiveness of lipid apheresis can only be estimated.     

LDL Hemoperfusion-A New Procedure for LDL Apheresis: First Clinical Application of an LDL Adsorber Compatible with Human Whole Blood

Abstract: To date, lipid apheresis procedures can remove low-density lipoprotein (LDL) cholesterol (LDL-C) only from plasma. Thus, initially plasma has to be separated from the blood cells, which increases the costs and complexity of the extracorporeal circuit. This paper describes the first clinical application of a new LDL adsorber that eliminates LDL directly from whole blood. The goal of this pilot study was to test the efficacy, safety, and feasibility of direct lipoprotein adsorption in patients. In a 2 center Phase II clinical trial, 12 hypercholesterolemic patients suffering from overt coronary or peripheral artery disease were treated once with LDL hemoperfusion. The new LDL adsorber (DALI, Fresenius, St. Wendel, Germany) contained 480 ml of polyacrylate coated polyacrylamide gel. The anticoagulation consisted of an initial heparin bolus followed by an acid citrate dextrose (ACD)-A infusion during the treatment. The processing of nearly 1 patient blood volume resulted in a reduction of LDL-C by 45 ± 8% and triglycerides by 23 ± 20%. HDL-C, fibrinogen, and cell counts were not significantly influenced. In a subgroup of 5 patients who exhibited elevated lipoprotein (a) (Lp[a]) levels, Lp(a) reduction was 43 ± 15% (all results corrected for plasma volume shifts). The sessions were clinically uneventful; the system was technically safe and easily handled. In conclusion, short-term LDL hemoperfusion by the DALI proved to be a safe, effective, and simple procedure for the treatment of patients suffering from symptomatic recalcitrant hypercholesterolemia. The present study represents a solid basis for the clinical long-term evaluation of this new technique in the future.     

Extracorporeal treatment of hypercholesterolaemia

Extracorporeal removal of LDL cholesterol (LDL apheresis) hasbeen carried out in patients with diet- and drug-resistant hypercholesterolaemiato prevent or to reduce coronary heart disease. Plasma separationis the first step in all five LDL-apheresis methods presentlyavailable. Plain plasma exchange and double-membrane filtrationare unselective and remove HDL cholesterol and plasma proteins.Adsorption of LDL to dextran sulphate, to LDL antibodies, orprecipitation of LDL by heparin at low pH are more selective.With all methods LDL cholesterol reduction per treatment is60–70%. In most patients one treatment per week is sufficientto reduce mean LDL to 100–150 mg/dl. Minor side-effectsoccur in 10±5% of treatments. Major side-effects arerare. Long-term LDL apheresis increased survival in patientswith homozygous familial hypercholesterolaemia. In heterozygousfamilial hypercholesterolaemia controlled studies regardingsurvival are not available. Uncontrolled trials indicate regressionof coronary artery disease in heterozygotes with drug- and diet-resistantLDL cholesterol > 200 mg/dl. Hence, LDL apheresis is indicatedin all patients with homozygous familial hypercholesterolaemia.LDL apheresis in heterozygous familial hypercholesterolaemiashould be restricted to patients with diet- and drug-resistantLDL cholesterol >200 mg/dl with coronary heart disease and/orother atherosclerotic vascular lesion.     

State of the Art of Lipid Apheresis

Abstract: Currently, 5 different lipid apheresis procedures are available for routine clinical treatment of hy–percholesterolemic patients. Unselective plasma exchange is a technically simple extracorporeal circuit, but albumin substitution fluid must be used and there is no high–density lipoprotein (HDL) recovery. Semiselective double filtration with improved size selectivity because of a small–pore secondary filter combines good elimination of low–density lipoprotein (LDL), lipoprotein (a) (Lp[a]), and fibrinogen with adequate HDL recovery; modifications such as thermofiltration, predilution/backflush, or pulsatile flow have been proposed for the improvement of this system. Three highly selective procedures are basedon immunologic or electrostatic interactions: immunoad–sorption using anti–low–density lipoprotein (LDL) antibodies, chemoadsorption onto dextran sulfate, and hep–arin–induced LDL precipitation (HELP) apheresis. The features of each system are discussed critically. Lastly, two new developments, Lp(a) immunoadsorption and LDL hemoperfusion using a polyacrylate LDL adsorber compatible with whole blood, are described     

Development of Immunosorbents for apoB-Containing Lipoproteins Apheresis

Abstract: Three types of sorbents were developed for the specific removal of atherogenic apoB-containing low-density lipoprotein (LDL) and lipoprotein LDL(a) (Lp[a])from human plasma. Two sorbents contained monospecific sheep polyclonal or mouse monoclonal antibodies against human apoprotein B-100. The third one was intended for specific removal of Lp(a) and contains sheep antibodies against human Lp(a). Thirty patients were treated for up to 9 years by LDL apheresis with anti-LDL immunosorbents. A pilot study of Lp(a) apheresis with 3 patients was conducted during 3 years. The results showed that extracorporeal immunosorption is safe and effective for lowering LDL and Lp(a). These procedures may be used both for metabolic investigations and for studies on possible regression of atherosclerosis.     

Serum Amyloid A and P Protein Levels are Lowered by Dextran Sulfate Cellulose Low-Density Lipoprotein Apheresis

The present study describes the short-term effect of dextran sulfate cellulose (DSC) low-density lipoprotein (LDL) apheresis using a plasma separator equipped with a polysulfone (PS) membrane filter (PS/DSC-LDL apheresis) on the serum amyloid A (SAA) and P (SAP) protein levels during treatment in a patient with familial hypercholesterolemia (type IIa, heterozygote). PS/DSC-LDL apheresis markedly lowered both the SAA (reduction percentage, 84.1 ± 8.2%) and SAP (91.4 ± 5%) levels, which returned to their respective initial levels within 4 days. Experimentally, the levels of both proteins also decreased on passage through the DSC minicolumn without a PS membrane, indicating that the DSC resin had an affinity to both proteins. These results suggest that PS/DSC-LDL apheresis may be advantageous for amyloid protein accumulating disorders, including amyloidosis and atherosclerosis.     

Assessment of Currently Available Low-Density Lipoprotein Apheresis Systems

Abstract: It has already been 10 years since the introduction of low-density lipoprotein (LDL) apheresis technologies. They have been established as technically and medically feasible for long-term treatment and economically acceptable, and their long-term treatment effects have been determined. Currently, there are efforts to develop more selective LDL removal systems. However, after 10 years of research, it is time to carefully review this strategy. The approach may have become too specific in light of the multiple macromolecules involved in the pathogenesis of atherosclerosis. In this paper, the six currently available LDL apheresis systems (plasma exchange, double filtration plasmapheresis, thermofiltration, LDL chemical adsorption (Kaneka system), LDL immunoadsorption, and the heparin-induced extracorporeal LDL precipitation [HELP] system) were reviewed and scored from various points of view such as effectiveness, simplicity, safety, and cost performance. Finally, each system was assessed from the global point of view in relation to the pathogenesis of lipid-related diseases.     

Extracorporeal treatment of familial hypercholesterolemia with monoclonal antibodies to low-density lipoprotein

Plasma exchange (PE) is considered the most effective nonsurgical treatment modality for the reduction of low-density lipoprotein (LDL) in patients with familial hypercholesterolemia (FH). However, the concomitant reduction of high-density lipoprotein (HDL) and the necessity and cost of using blood products are major drawbacks of PE. We studied the effects of selective LDL reduction using monoclonal anti-LDL antibodies in an investigational immunoadsorption (IA) system. Results were compared with the effects of PE. During the study period, two homozygous FH patients with baseline cholesterol levels greater than 10.34 mmol/L (400 mg/dL) were treated sequentially for a combined total of 37 IA treatments and the results were compared with a total of 19 sequential PE treatments. The IA system consisted of on-line plasma processing over two columns of monoclonal anti-LDL antibodies in alternating cycles of column adsorption and regeneration. No replacement solution was needed. PE was performed with a centrifugal plasma separator using 5% albumin as replacement solution. Results showed that the reduction of lipids with IA was 43% +/- 0.9% for cholesterol, 51% +/- 1.0% for LDL, and 19% +/- 1.3% for HDL, resulting in a reduction in the LDL to HDL ratio of 41% +/- 1.7%. Compared with IA, percent reduction by PE was significantly greater (P less than 0.001) for all lipids, but was nonselective (cholesterol, 74% +/- 1.0%; LDL, 77% +/- 1.2%; HDL, 73% +/- 2.7%), and therefore the reduction of the LDL to HDL ratio was only 6% +/- 3.6%, which was significantly less than for IA (P less than 0.001). Pretreatment HDL concentration appeared to increase with repetitive IA treatment, but decreased back to prestudy levels with repetitive PE.(ABSTRACT TRUNCATED AT 250 WORDS)     

Evaluation of Double Filtration Plasmapheresis, Thermofiltration, and Low–Density Lipoprotein Adsorptive Methods by Crossover Test in the Treatment of Familial Hypercholesterolemia Patients

Abstract: A comparative assessment has been made regarding efficacy and safety of the double filtration plasmapheresis (DFPP), thermofiltration (TFPP), and low–density lipoprotein (LDL) adsorptive (PA) methods by making a crossover test on heterozygous familial hypercholesterolemia patients. Treatments by DFPP, TFPP (secondary membrane Evalux 5A), and PA (Liposorber LA–40) were carried out 5 times each, with a 2–week interval, in 5 patients with heterozygous familial hypercholesterolemia. The same plasma separator (Plasmacure PS–60, polysulfone) was used in all cases, and the volume of plasma processed was set at 4 L. High removal rates were obtained of total cholesterol, LDL cholesterol, triglycerides TG, and apolipoprotein B (apoB) by all three methods, and no differences were observed. Lipoprotein (a), apoA–2, apoC–3, fibrinogen, and immunoglobulin M (IgM) showed significantly high removal rates by the DFPP and TFPP methods compared with the PA method.
The sieving coefficient of albumin and high–density lipoprotein (HDL) cholesterol at 2 and 4 L of plasma processed exhibited high permeabilities using all three methods. Supplementing albumin was not necessary. An increase of the transmembrane pressure was observed in 1 case treated by DFPP but was not observed when using the TFPP or PA method. No changes were observed in serum interleukin 1β (IL–lβ) or tumor necrosis factor–a (TNF–α) before and after treatment by any of the three methods. No remarkable side effects were observed using either the DFPP or TFPP method. The DFPP and TFPP methods showed efficacy and safety that was not inferior to the PA method in conventional LDL apheresis, and the dead–end method of the filter operation without the discarding of plasma was shown to be possible.     

Different Apheresis Methods in the Treatment of Hypercholesterolemia in Primary Biliary Cirrhosis: A Case Report

Abstract: The two different modes of low–density lipoprotein (LDL) apheresis, cascade filtration (CF) and dextransulfate cellulose (DSC) adsorption, were compared for efficiency of cholesterol removal in a patient with severe hypercholesterolemia due to primary biliary cirrhosis (PBC). Decrement in the total cholesterol level by the DSC method was less than that by the CF method. Apolipoprotein B was decreased to almost null by both modules whereas the decrease in albumin was much greater in the second filter of the CF method than in the DSC column. Lipoprotein X which constituted the major portion of serum cholesterol in PBC became negative by passing plasma through the second filter. The CF method was preferred to the DSC method for removal of lipoprotein X, but albumin substitution was mandatory to prevent the decrease of serum albumin in the CF method.