Low-density lipoprotein apheresis using the Liposorber system: features of the system and clinical benefits.

LDL apheresis using the Liposorber system is indicated for use to remove selectively LDL from the plasma of hypercholesterolemic patients for whom diet and maximum cholesterol-lowering drug therapy have been ineffective or not tolerated. The dextran sulfate immobilized to porous cellulose beads is contained in the adsorption column as the adsorbent. The dextran sulfate has a structure similar to that of the LDL receptor and seems to act as a type of pseudoreceptor for LDL. There have been reported a number of clinical benefits using the Liposorber system for drug refractory hypercholesterolemic patients. Among them, the improvement of endothelial cell function of coronary and brachial arteries by a single treatment is the focus of the world's attention. Moreover, it is also noteworthy that LDL apheresis reduced the incidence of the cardiac events by 70% compared to drug therapy alone. In addition to the clinical benefits of the Liposorber system on familial hypercholesterolemia (FH), the preliminary data suggest that LDL apheresis may improve arteriosclerosis obliterans (ASO) of the lower extremities and focal glomerular sclerosis (FGS).     

Clinical experience and future directions for low-density lipoprotein apheresis in the United States.

The United States Liposorber Study was a 22 week randomized controlled study of low-density lipoprotein (LDL) apheresis with an optional follow-up phase. The procedure was found to acutely lower LDL cholesterol by up to 81%, have good tolerability, and produce a reduction in the frequency of cardiovascular events. Studies outside the United States have found therapy with LDL apheresis to be associated with a favorable clinical outcome including improved myocardial perfusion, but variable regression of coronary artery disease (CAD). Improvement in blood viscosity and endothelial function may help explain the symptomatic benefits observed with relatively small changes in angiography. Based upon favorable clinical experience, LDL apheresis using dextran sulfate cellulose columns has recently received approval for commercialization in the United States in patients with inadequate responses to diet and drug therapy and LDL levels > or = 200 mg with CAD present or LDL levels > or = 300 mg/dl without CAD.     

Low-density lipoprotein apheresis reduces platelet factor 4 on the surface of platelets: a possible protective mechanism against heparin-induced thrombocytopenia and thrombosis

BACKGROUND: Heparin‐induced thrombocytopenia and thrombosis (HITT) is characterized by thrombocytopenia due to the formation of antibodies against heparin : platelet factor 4 (PF4) complexes. Despite the exposure to heparin during treatment and predisposition of patients with atherosclerosis to HITT, HITT in patients undergoing low‐density lipoprotein (LDL) apheresis is rare. We investigated the possibility that LDL apheresis decreases PF4 on platelet (PLT) surfaces and/or plasma HITT antibody levels, either of which would disfavor HITT. STUDY DESIGN AND METHODS: We enrolled 25 patients undergoing LDL apheresis at the Hospital of the University of Pennsylvania. Blood samples were drawn before and after treatment. Plasma samples were drawn proximal and distal to the LA‐15 treatment column. PF4, HITT antibodies, heparin levels, and P‐selectin were measured. RESULTS: No patient had clinical symptoms of HITT. The LA‐15 column was found to efficiently remove PF4. PF4 levels in peripheral blood plasma did not change significantly after LDL apheresis. However, PLT surface PF4 significantly decreased after treatment. HITT antibodies were found in only two patients and were nonfunctional. PLT surface P‐selectin did not change during treatment. CONCLUSIONS: We have demonstrated that LDL apheresis via dextran sulfate absorption removes plasma PF4 and reduces the amount of PF4 on the surface of circulating PLTs. Reduced surface PF4 may decrease antibody formation and/or recognition by HITT antibodies. These data provide a potential explanation for the near lack of HITT in hypercholesterolemic patients undergoing LDL apheresis. They also suggest the possibility that LDL apheresis using dextran sulfate adsorption may have therapeutic value in the treatment of HITT.     

The role of low density lipoprotein apheresis in the treatment of familial hypercholesterolemia.

The chief indication for low density lipoprotein (LDL) apheresis is the treatment of homozygous familial hypercholesterolemia (FH), a potentially fatal condition that responds poorly to conventional therapy. Dextran sulfate/cellulose adsorption columns (Kaneka) and on-line heparin precipitation (HELP) are the most popular systems used in LDL apheresis. Weekly or biweekly procedures plus concomitant drug therapy enable LDL cholesterol to be maintained at 30-50% of its untreated level, with regression of xanthomas, arrest of progression of coronary atherosclerosis, and improved life expectancy. However, aortic stenosis may progress despite apheresis and necessitate valve replacement. Better control of hypercholesterolemia results from combining apheresis with a new 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, atorvastatin. LDL apheresis can also be useful in treating drug-resistant FH heterozygotes with coronary disease. However, the FH Regression Study showed no evidence that reduction by apheresis of both LDL and lipoprotein(a), was more advantageous than reduction by combination drug therapy of LDL alone.     

Therapeutic apheresis in low weight patients: technical feasibility, tolerance, compliance, and risks.

The use of therapeutic apheresis in very low weight patients is generally thought to have limitations, because of possible severe adverse reactions, potential risk related to the extracorporeal procedure, due to the low weight of the young patients. A careful therapeutic approach using appropriate precautions, and also introducing modifications to the standard procedure, can minimise the risk without compromising the efficacy of the plasmapheresis. The aim of the study was to evaluate apheresis tolerance and acceptability in children [Artif. Organs. 21 (1997) 1126] and infants [J. Clin. Apheresis 5 (1989) 21] with inherited lipid metabolism disorder, familial hypercholesterolemia (FH), primary hyperlipoproteinemia (lipoprotein phenotype I), and acute leukemia, weighing on average 20.55 kg. One thousand one hundred twenty three aphereses were completed. Three types of apheresis were performed: leukapheresis, plasma exchange, dextran sulphate cellulose (DSC) low density lipoprotein (LDL)-apheresis. Three different types of continuous flow systems were used. Technical adaptation depending on patients blood volume, body mass index, hematocrit, type of system used, permitted us to perform complete aphereses, obtaining a high degree of tolerance and acceptability of the treatment. The use of plasmapheresis is regarded to be an extreme therapeutic measure in children. However, when the need for such treatment is undebatable, plasmapheresis must be done. A well-trained and experienced team can overcome the technical difficulties in order to complete the procedures without complications. The most frequently observed adverse effects are vascular relative access insufficiency (2.0%), and mild hypotension (2.0%).     

Three low density lipoprotein apheresis techniques in treatment of patients with familial hypercholesterolemia: a long-term evaluation.

Low density lipoprotein (LDL) apheresis is a treatment option for patients with severe hypercholesterolemia not adequately responding to drug treatment who have developed coronary heart disease. We regularly treated 18 patients with immunoadsorption, 8 with heparin induced extracorporeal LDL precipitation (HELP) and 8 with dextran sulfate adsorption for a mean of 4.6 +/- 2.6 years. The effects on LDL cholesterol, high density lipoprotein (HDL) cholesterol, and lipoprotein (a) were comparable among all 3 techniques. Twelve patients were treated for longer than 5 years and 18 patients for longer than 3 years. The evaluation of coronary angiograms (23 patients) revealed a definite regression of coronary lesions in 3 patients; in all other patients, there was a halt in progression. Three patients suffered a sudden cardiac death and 1 patient a nonfatal myocardial infarction due to the occlusion of a coronary bypass. In 9 of 11 patients, no atherosclerotic lesions developed in the coronary bypasses. No severe side effect of either procedure was observed. In conclusion, aggressive lipid lowering by LDL apheresis can stabilize coronary atherosclerosis in most patients.     

LDL apheresis in clinical practice: long-term treatment of severe hyperlipidemia.

Thirty patients (13 males, 17 females) suffering from familial hypercholesterolemia resistant to diet and lipid-lowering drugs were treated for 48.7 +/- 19.2 months (range, 2-87 months) with low density lipoprotein (LDL) apheresis. Three different systems (dextran sulfate adsorption for 27 of 30 [Kaneka, Liposorber, Japan], immunoadsorption system for 2 of 30 [Baxter, Therasorb, Germany], immunoadsorption system with special lipoprotein a [Lp(a)] columns for 1 of 30 patients [Lipopak, Pocard, Russia]) were applied. Before LDL apheresis 24 of 30 patients suffered from coronary heart disease (CHD) with angina symptoms. With LDL apheresis, reductions of 46% for total cholesterol, 49% for LDL, 30% for Lp(a), and 38% for triglycerides were reached. Severe side effects such as shock or allergic reactions were very rare (0.5%). In the course of treatment, an improvement in general well-being and increased performance were experienced in 27 of 30 patients. A 60 to 100% reduction of nitrate medication was observed in 17 of 24 patients. Regarding the different apheresis systems used, at the end of the trial there were no significant differences with respect to the clinical outcome experienced by the patients and concerning total cholesterol, LDL, high density lipoprotein, and triglyceride concentrations. But to reduce high Lp(a) levels, the immunoadsorption method with special Lp(a) columns seems to be the most effective (-57% versus 25% [Kaneka] and 23% [Baxter]). The present data clearly demonstrate that treatment with LDL apheresis of patients suffering from familial hypercholesterolemia, resistant to maximum conservative therapy, is very effective and safe, even in long-term application.     

Effects of losartan on low-density lipoprotein apheresis.

The negative charges of dextran sulfate cellulose (DSC) used for low-density lipoprotein (LDL) apheresis activate the intrinsic coagulation pathway, accompanied by bradykinin production. This study was undertaken to see whether an antagonist of angiotensin receptor (AT1), losartan, could be safely used in a patient treated by DSC-LDL apheresis. Losartan (50 mg/day) was given to a patient with coronary heart disease who had been treated by DSC-LDL apheresis and had experienced an anaphylactoid reaction by administration of an angiotensin converting enzyme inhibitor. The effects of losartan on blood pressures and humoral factors were examined by comparing these parameters between apheresis with and without losartan. Blood pressures and plasma levels of bradykinin, renin, and aldosterone were measured before and at 1,000, 2,000, and 3,000 ml of plasma treatment. Bradykinin levels during LDL apheresis tended to be higher with losartan than without losartan (without versus with, 529 +/- 121 [n = 4, mean +/- SE] pg/ml vs. 1,058 +/- 49 at the 2,000 ml stage, p < 0.01). The rise of plasma renin activity with losartan (221 +/- 26% at the 3,000 ml stage) was significantly greater than that without losartan (144 +/- 2.4%). Mean blood pressure decreased by 7% during apheresis with losartan, but blood pressure reduction was not accompanied by any complaints. These results suggest that AT1 receptor antagonists are safely used in patients treated by DSC-LDL apheresis.     

Effects of selective LDL apheresis on plasma concentrations of ICAM-1, VCAM-1 and P-selectin in diabetic patients with arteriosclerosis obliterans and receiving maintenance hemodialysis

BACKGROUND: Arteriosclerosis obliterans (ASO) is a serious complication in patients with end-stage renal disease (ESRD) caused by diabetic nephropathy. Adsorption of low-density lipoprotein (LDL) has been performed to treat ASO. While efficacy of this treatment has been reported in limb ischemia, the mechanism underlying the benefit remains unclear. We investigated how LDL adsorption affected soluble adhesion molecules; P-selectin, an endothelial and platelet activation marker; inflammatory cytokines such as interleukin (IL)-1beta, IL-6 and tissue necrosis factor (TNF)-alpha; and lipids in serum. METHODS: Selective LDL adsorption by dextran sulfate columns (LDL apheresis) was performed weekly for 10 weeks to treat eight hemodialysis patients with ASO, ESRD, and type 2 diabetes mellitus. Serum was sampled before and immediately after apheresis. RESULTS: LDL apheresis was performed safely. After LDL apheresis lipid concentrations were significantly reduced and clinical findings, such as Fontaine's classification and ankle brachial pressure index values, were improved. Pretreatment concentrations of soluble intercellular and vascular cell adhesion molecules (sICAM-1 and sVCAM-1) and also P-selectin were higher in patients than healthy controls. After apheresis these decreased, especially P-selectin. IL-1beta, IL-6, and TNF-alpha concentrations before apheresis were similar to those in controls and were unaffected by treatment. CONCLUSION: Effectiveness of LDL apheresis against ASO may involve decreased endothelial cell and platelet activation.     

Therapeutic selective adsorption of anti-DNA antibody using dextran sulfate cellulose column (Selesorb) for the treatment of systemic lupus erythematosus.

The Selesorb therapeutic dextran sulfate cellulose column (Kaneka Corporation, Osaka, Japan) selectively adsorbs anti-DNA antibody, anti-cardiolipin antibody, and immune complex from the plasma of patients with systemic lupus erythematosus (SLE). The Selesorb system is composed of twin columns attached to an automated regeneration apheresis unit. Anti-DNA antibody in plasma is continuously removed through 1 of the 2 columns alternately. Clinical application of the Selesorb system to SLE patients with high titers of anti-DNA antibody showed improvement of proteinurea, arthralgia, rash, lymphocytopenia, etc., with the concurrent use of steroid and/or immnosuppressant. Angiotensin converting enzyme inhibitor should not be administered to patients treated with the Selesorb system to avoid anaphylactoid reactions based on rapid increases of bradykinin concentrations in the blood.     

Extracorporeal circuit heparinization in selective low density lipoprotein apheresis: Changes in patient hemostasis and low molecular weight heparin benefit

Treatment by low density lipoprotein (LDL) apheresis using dextran sulfate columns (DSC) leads to hemostasis alterations with prolonged activated partial thromboplastin time (APTT) of more than 120 seconds. In order to explain this hypocoagulability, we studied hemostasis parameters both in patients and in the extracorporeal circulation (ECC). Hemostasis changes are first related to unfractionated heparin (UFH)—needed to avoid circuit coagulation—which leads to high residual heparinemia in the patient (more than 3 times the recommended level for therapeutic use). Second, the hypocoagulability is induced by a coagulation factor decrease (primarily factors V, VIH, and X) mainly due to an adsorption mechanism on dextran sulfate. Studies on samples from column inflow, outflow, and eluate confirm this mechanism. Low molecular weight heparin (LMWH) can be used in LDL apheresis on DSC without major changes in lipid removal or coagulation factors compared to UFH. The benefit of using LMWH is to reduce residual heparinemia into the therapeutic range. © 1993 Wiley-Liss, Inc.     

Application of a new LDL apheresis system using two dextran sulfate cellulose columns in combination with an automatic column-regenerating unit and a blood cell separator

Extracorporeal procedures for selective removal of low-density lipoproteins have become a promising new approach for treatment of severe familial hypercholesterolemia. We tested efficacy and safety of a new LDL apheresis system by using two dextran sulfate cellulose adsorbents (Liposorber LA 15TM from Kanegafuchi) under the control of an automatic column-regenerating unit for continuous alternate adsorption and desorption. Plasma was taken from a continuous-flow blood cell separator (model IBM/Cobe 2997) allowing an extracorporeal circuit from one cubital vein to another. A 57-year-old male with drug-resistant heterozygous familial hypercholesterolemia accompanied by moderate hypertriglyceridemia and severe coronary artery disease has been treated every 2 weeks for 3 months so far. Treatment of 4-5 liters of plasma resulted in a mean decrease of total cholesterol from 355 to 111 mg/dl (9.20 to 2.88 mmol/l), of LDL cholesterol from 272 to 49 mg/dl (7.05 to 1.53 mmol/l), and of apolipoprotein B from 175 to 44 mg/dl. HDL cholesterol, apolipoprotein A-I, and other plasma proteins did not substantially change apart from hemodilution. No side effects were seen. This new technique of LDL apheresis represents a very effective and safe method for treatment of drug-resistant familial hypercholesterolemia without or with concomitant hypertriglyceridemia.     

Analysis of protein absorbed by LDL column (Liposorber) with special reference to complement component factor D

BACKGROUND: A dextran sulfate column (Liposorber) has been developed and proven effective in LDL apheresis for removing LDL from patients with hyperlipemia. Chronic renal failure (CRF) patients with arteriosclerosis obliterans (ASO) treated with Liposorber have been shown good results. METHODS: We analyzed proteins absorbed by Liposorber in CRF patients with ASO by means of 2-dimensional electrophoresis and found some noteworthy protein spots. One of these proteins was purified by Sephacryl S-100 column and DEAE Sepharose fast flow column chromatography. RESULTS: The purified protein was finally identified as complement factor D by Western blotting. The average of recovery amount from three experiments was 6.5 mg. The total recovered amount of factor D was calculated to be about 21.7% out of the estimated amount of factor D in the plasma of CRF patients with ASO receiving LDL apheresis using Liposorber. CONCLUSIONS: These results indicate that Liposorber absorbs factor D remarkably well.     

Current topics on low-density lipoprotein apheresis.

The prognosis of patients suffering from severe hyperlipidemia, sometimes combined with elevated lipoprotein (a) (Lp[a]) levels, and coronary heart disease (CHD) refractory to diet and lipid-lowering drugs is poor. For such patients, regular treatment with low-density lipoprotein (LDL) apheresis is the therapeutic option. Today, there are four different LDL-apheresis systems available: immunoadsorption, heparin-induced extracorporeal LDL/fibrinogen precipitation, dextran sulfate LDL-adsorption, and LDL-hemoperfusion. Despite substantial progress in diagnostics, drug therapy, and cardiosurgical procedures, atherosclerosis with myocardial infarction, stroke, and peripheral cellular disease still maintains its position at the top of morbidity and mortality statistics in industrialized nations. Established risk factors widely accepted are smoking, arterial hypertension, diabetes mellitus, and central obesity. Furthermore, there is a strong correlation between hyperlipidemia and atherosclerosis. Besides the elimination of other risk factors, in severe hyperlipidemia (HLP) therapeutic strategies should focus on a drastic reduction of serum lipoproteins. Despite maximum conventional therapy with a combination of different kinds of lipid-lowering drugs, however, sometimes the goal of therapy cannot be reached. Mostly, the prognosis of patients suffering from severe HLP, sometimes combined with elevated Lp(a) levels and CHD refractory to diet and lipid-lowering drugs is poor. Hence, in such patients, treatment with LDL-apheresis can be useful. Regarding the different LDL-apheresis systems used, there were no significant differences with respect to the clinical outcome or concerning total cholesterol, LDL, high-density lipoprotein, or triglyceride concentrations. With respect to elevated Lp(a) levels, however, the immunoadsorption method seems to be the most effective. The published data clearly demonstrate that treatment with LDL-apheresis in patients suffering from severe hyperlipidemia refractory to maximum conservative therapy is effective and safe in long-term application.     

Comparison of different treatment regimens in a case of homozygous familial hypercholesterolemia.

The laboratory results of five periods of different treatment regimens were compared in a 19-year-old girl with homozygous familial hypercholesterolemia (FH): weekly low-density lipoprotein (LDL) apheresis sessions with dextran sulfate columns (LA 15, Kaneka Corporation, Osaka, Japan) without statin administration; weekly LDL apheresis with polyacrylate columns (DALI, Fresenius Adsorber Technology, Bad Homburg, Germany) without statin; LDL apheresis as in Period 2 with 40 mg atorvastatin daily; LDL apheresis as in Period 2 with 80 mg atorvastatin daily; and fortnightly LDL apheresis sessions with polyacrilate and administration of 80 mg atorvastatin daily. The five treatments were given in the above order, and each lasted at least 2 months. To compare the effectiveness of the different methods, the blood levels of total cholesterol, LDL-cholesterol and high-density lipoprotein (HDL)-cholesterol were measured before each session, and the percentage decreases in the blood levels of total cholesterol and LDL-cholesterol were recorded during sessions in Periods 1 and 2. In Periods 1 and 2, the biological effectiveness of LDL apheresis was comparable. Atorvastatin (40 mg daily) improved the blood levels of total cholesterol and LDL-cholesterol, but lowered HDL-cholesterol values. Increasing the daily dose of atorvastatin from 40 mg to 80 mg did not significantly improve LDL-cholesterol levels. When the time between two sessions was longer (Period 5), the total cholesterol and LDL-cholesterol values worsened and were comparable to those of Period 2 during which there was no atorvastatin treatment. In this case of homozygous FH, weekly sessions of LDL apheresis in association with atorvastatin at dose of 40 mg per day gave the best results.     

Low-density lipoprotein apheresis using the liposorber dextran sulfate cellulose system for patients with hypercholesterolemia refractory to medical therapy

A subset of patients with familial hypercholesterolemia (FH) have an inadequate lipid-lowering response to diet and drug treatment and should be considered for low-density lipoprotein (LDL)-apheresis therapy. This procedure selectively removes apolipoprotein B-containing particles [LDL, very-low-density lipoprotein, lipoprotein(a)] from plasma independent of diet and drug therapy. Methods for performing LDL-apheresis include dextran sulfate cellulose adsorption, immunoadsorption, and heparin-induced extracorporeal precipitation. The Liposorber Study Group evaluated LDL removal using the Liposorber® LA-15 LDL-apheresis System in 64 patients with FH who had not responded adequately to diet and maximal drug therapy. Mean acute reductions in LDL cholesterol (LDL-C) were 76% in heterozygous FH (HtFH) patients and 81% in homozygous FH (HoFH) patients. Time-averaged levels of LDL-C were lowered 41% in HtFH and 53% in HoFH patients. Hypotension was the most frequent side effect, occurring in 3% of procedures. The Liposorber® LA-15 System has been approved by the Food and Drug Administration and is recommended for 1) patients with functional homozygous FH (LDL-C level >500 mg/dL; 2) patients with coronary artery disease (CAD) and LDL-C levels ≥200 mg/dL; 3) patients without CAD, but an LDL-C level ≥300 mg/dL. © 1996 Wiley-Liss, Inc.     

Anti-dsDNA antibody kinetics during in vivo apheresis in systemic lupus erythematosus patients and in an in vitro apheresis model

Levels of anti-dsDNA measured just after an immunoadsorption procedure in systemic lupus erythematosus (SLE) patients are sometimes paradoxically larger than those measured just before the procedure. A 1:100 in vitro single-compartment immunoadsorption system model was devised to determine which of two models, one- or two-compartment, more closely approximates the kinetics of anti-dsDNA during apheresis procedures. Ten SLE patients were employed in this study. A total of 4,100 ml of plasma was passed through the dextran sulfate cellulose columns during one clinical apheresis session. In eight of ten patients, the log of RIA-measured anti-dsDNA titers decreased linearly as treated plasma volume increased, in both the clinical procedure and the experimental model. The mean adsorption efficacy in the clinical apheresis procedure and in the in vitro model was 0.37 and 0.27, respectively. However, in one patient the RIA-measured level of anti-dsDNA increased during the apheresis procedure; this phenomenon was mirrored in the model (definitely a single pool model). In contrast, the level of anti-dsDNA, as measured by ELISA, decreased in accordance with the increase of treated plasma volume in both the clinical and the in vitro apheresis procedures. Therefore, an increased titer of anti-dsDNA as measured by RIA immediately following clinical apheresis cannot be accounted for exclusively by an inflow of antibodies from a secondary (extravascular) pool into the circulating plasma. In short, a one-compartment model is applicable and an explanation must be sought elsewhere. © 1996 Wiley-Liss, Inc.     

Changes in Iipoprotein(a), LDL-cholesterol and apolipoprotein B in homozygous familial hypercholesterolaemic patients treated with dextran sulfate LDL-apheresis

Abstract. We evaluated the effect of periodical treatment with LDL-apheresis by adsorption to dextran sulfate (Liposorber LA-15) on several aspects related to LDL and Lipoprotein(a) metabolisms, in three homozygous familial hypercholesterolaemic patients with LDL receptor deficiency. The dextran sulfate columns retained apolipoprotein B-containing particles with high affinity and capacity, in such a way that the treatment of a volume of plasma equivalent to three times the patient plasma volume resulted in an 85% decrease of circulating LDL-cholesterol and Lipoprotein(a). The continuous treatment with LDL-apheresis was highly beneficial for these patients since an average plasma concentration lower than 200 mg dl-′ for LDL-cholesterol, and lower than 25 mg dl^-′ for Lipoprotein(a) could be achieved by treating the patients once a week. After each apheresis treatment, plasma concentrations of these metabolites progressively returned to the pretreatment, steady-state, levels. The analysis of the rates of return allowed us to estimate the fractional catabolic rates. FCRs of LDL-cholesterol were 0–052, 0.049 and 0.047 pools day^-1, and those of apolipoprotein B, 0.065, 0.045 and 0.050 pools day^-1 in the three subjects, respectively. These values are much lower than those in normolipidaemic individuals as observed by others, and are in accordance with the LDL-receptor deficiency condition of our patients. Two of them had highly elevated Lipo-protein(a) plasma concentrations, and their FCRs of Lipoprotein(a) were calculated to be 0.112 and 0.066 pools day^-1. These values were significantly higher than the respective FCR of LDL-cholesterol and apolipoprotein B, which demonstrates that Lipopro-tein(a) and LDL were not metabolically homogeneous in these patients. Values of -kt for Lipoprotein(a), LDL-cholesterol and apolipoprotein B correlated during the first days inmediately after each apheresis session, suggesting that production of Lipoprotein(a) in these individuals was associated to that of apolipoprotein B. It is proposed that elevated Lipoprotein(a) plasma levels in familial hypercholesterolaemia are mainly a consequence of a high production rate rather than decreased fractional catabolic rate.     

Dextran-sulfate-adsorption of atherosclerotic lipoproteins from whole blood or separated plasma for lipid-apheresis--comparison of performance characteristics with DALI and Lipidfiltration

For many years dextran sulfate adsorption (DSA) treatment of separated plasma has been an established technology for low-density lipoprotein (LDL)-elimination. Recently a system for the treatment of whole blood based on DSA was introduced into clinical practice. To further characterize DSA treatment of whole blood, the performance characteristics of both DSA modalities were compared at two investigational sites with two alternative LDL apheresis systems being already in routine clinical use. In prospective cross-over design, DSA whole blood treatment was compared with a whole blood polyacrylate LDL adsorption system (DALI) in one study group. DSA for plasma treatment was compared with Lipidfiltration in cross-over design in a second study group. In total, 12 patients on chronic LDL apheresis received 169 treatments. Six patients were treated twice with whole blood polyacrylate adsorption and twice with whole blood DSA. LDL-cholesterol (74.9-78.0%) and lipoprotein (a) (72.1-73.3%) were reduced by both with equal efficacy. DSA achieved a significantly higher reduction rate of fibrinogen. Another six patients were treated eight times with DSA plasma adsorption followed by 16 Lipidfiltration treatments. LDL-cholesterol (67.0-70.2%) and lipoprotein (a) (69.2-73.7%) were reduced by both with equal efficacy. Fibrinogen was eliminated more efficiently by Lipidfiltration (50.2 vs. 38.5%). DSA proved to be a safe and effective in both treatment modes, for plasma as well as for whole blood. At the discretion of the apheresis specialist, depending upon the status of national approval, DSA of whole blood complements the armamentarium of powerful modalities for extracorporeal elimination of atherosclerotic lipoproteins to meet specific individual, medical, or logistic needs.     

Efficacy of different low-density lipoprotein apheresis methods.

Low-density lipoprotein (LDL) apheresis is a treatment option in patients with coronary heart disease and drug resistant hypercholesterolemia. Various apheresis systems based on different elimination concepts are currently in use. We compared the efficacy of 4 different apheresis systems concerning the elimination of lipoproteins. The study included 7 patients treated by heparin extracorporeal LDL precipitation (HELP), 10 patients treated by immunoadsorption, 8 patients treated by dextran-sulfate adsorption, and 4 patients treated by cascade filtration. Ten subsequent aphereses were evaluated in patients undergoing regular apheresis for more than 6 months. Total cholesterol decreased by approximately 50% with all 4 systems. LDL cholesterol (LDL-C) (64-67%) and lipoprotein a [Lp(a)] (61-64%) were decreased more effectively by HELP, immunoadsorption, and dextran-sulfate apheresis than by the less specific cascade filtration system [LDL-C reduction 56%, Lp(a) reduction 53%]. Triglyceride concentrations were reduced by 40% (dextran-sulfate) to 49% (cascade filtration) and high-density lipoproteins (HDL) by 9% (dextran-sulfate) to 25% (cascade filtration). On the basis of plasma volume treated, HELP was the most efficient system (LDL-C reduction 25.0%/L plasma), followed by dextran-sulfate (21.0%/L plasma), cascade (19.4%/L plasma), and immunoadsorption (17.0%/L plasma). However, a maximal amount of 3 L plasma can be processed with HELP due to concomitant fibrinogen reduction while there is no such limitation with immunoadsorption. Therefore, the decision of which system should be used in a given patient must be individualized taking the pre-apheresis LDL concentration, concomitant pharmacotherapy, and fibrinogen concentration into account.