LDL Hemoperfusion-A New Procedure for LDL Apheresis: Biocompatibility Results from a First Pilot Study in Hypercholesterolemic Atherosclerosis Patients

Abstract: Current lipid apheresis techniques can remove atherogenic lipoproteins only from plasma. The initial mandatory separation of plasma and blood cells renders the extracorporeal circuit complex. We recently described the first clinical application of a new lipid adsorber that adsorbs low-density lipoprotein (LDL) and lipoprotein (a) (Lp[a]) directly from whole blood. In continuation of our work, this paper describes the clinical biocompatibility of this new LDL hemoperfusion system. 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 protocol consisted of an initial heparin bolus followed by an acid citrate dextrose-A (ACD-A) infusion during the treatment. One patient blood volume was treated per session. All sessions were clinically un eventful. No signs of hemolysis or extracorporeal clot formation could be detected, and cell counts remained virtually constant. In a subgroup of patients (n = 4–6), further biocompatibility parameters were studied. Activation of leukocytes (elastase release), thrombocytes (β-thrombo-globulin [β-TG] extrusion), and monocytes (interleukin (IL)-1β and IL-6) were minimal. Complement activation (C3a and C5a generation) was negligible. The chosen anticoagulation protocol was both safe (constant ionized calcium levels) and effective (low thrombin-antithrombin formation). In summary, within the scope of a first pilot study. this new LDL hemoperfusion procedure combined the features of excellent clinical tolerance, good biocompatibility, and ease of handling. Phase III clinical trials will have to show whether these encouraging preliminary results can be corroborated in a larger patient population.     

DALI apheresis in hyperlipidemic patients: biocompatibility, efficacy, and selectivity of direct adsorption of lipoproteins from whole blood

Recently, the first apheresis technique for direct adsorption of low-density lipoprotein (LDL) and lipoprotein(a) [Lp(a)] from whole blood (DALI) was developed that does not require a prior plasma separation. That markedly simplifies the extracorporeal circuit. The aim of the present study was to test the acute biocompatibility, efficacy, and selectivity of DALI apheresis. In a prospective clinical study, 6 hypercholesterolemic patients suffering from angiographically proven atherosclerosis were treated 4 times each by DALI. 1.3 patient blood volumes were treated per session at blood flow rates of 60-80 ml/min using 750 or 1,000 ml of polyacrylate/polyacrylamide adsorber gel. The anticoagulation consisted of an initial heparin bolus followed by a citrate infusion. The sessions were clinically essentially uneventful. Mean corrected reductions of lipoproteins amounted to 65% for LDL-cholesterol, 54% for Lp(a), 28% for triglycerides, 1% for HDL-cholesterol, and 8% for fibrinogen. The selectivity of lipoprotein removal was high. Cell counts remained virtually unchanged and no signs of hemolysis or clotting were detected. Cell activation parameters elastase, beta-thromboglobulin, interleukin-1beta, and IL-6 showed no significant increase. Complement activation was negligible. There was significant, but clinically asymptomatic, bradykinin activation in the adsorber with mean maxima of 12,000 pg/ml in the efferent line at 1,000 ml of treated blood volume. In conclusion, DALI proved to be safe, selective, and efficient for the adsorption of LDL-C and Lp(a), which simplifies substantially the extracorporeal therapy in hypercholesterolemic patients.     

Low–Density Lipoprotein Hemoperfusion Using a Modified Polyacrylate Adsorber: In Vitro, Ex Vivo, and First Clinical Results

Abstract: Current lipid apheresis techniques can remove low–density lipoprotein (LDL) cholesterol only from plasma, i.e., a primary cell–plasma separation step is mandatory. This article describes in vitro, ex vivo, and clinical results using a new LDL adsorber compatible with human whole blood. It consists of modified polyacrylate, the negative charges of which can interact with the positively charged protein B moiety of LDL, thus retaining these particles on the surface of the adsorber. After the efficacy and selectivity of LDL removal had been demonstrated in vitro and ex vivo, a clinical pilot study corroborated these results. Thus, treating 60 ml of blood per kilogram of body weight in a single session, LDL hemoperfusion reduced LDL cholesterol by 50%, lipoprotein (a) by 17%, and triglycerides by 19% in 6 hy–percholesterolemic patients. High–density lipoprotein cholesterol recovery amounted to 97%. In conclusion, LDL hemoperfusion holds great promise for the future.     

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     

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.     

Lipid Apheresis by Hemoperfusion: In Vitro Efficacy and Ex Vivo Biocompatibility of a New Low-Density Lipoprotein Adsorber Compatible with Human Whole Blood

Abstract: To date, selective extracorporeal low-density lipoprotein (LDL) removal can only be performed from plasma; that is, a plasma-cell separation step using a centrifuge or a plasma membrane separator is necessary initially. This article characterizes a new polyacrylate-based LDL adsorber directly applicable to whole blood . In vitro single-pass hemoperfusion tests using pooled donor blood showed quantitative adsorption of atherogenic LDL-cholesterol (LDL-C) and complete recovery of protective high-density lipoprotein C. Fibrinogen, another independent risk factor of atherosclerosis, was also adsorbed to a lesser extent. Single-pass ex vivo biocompatibility using fresh donor blood on-line was excellent and resulted in minimal cell loss. Neither signs of hemolysis nor activation of monocytes (interleukin-l production) were detected. Only slight activation of leukocytes (elastase release) and thrombocytes (platelet factor 4 secretion) as well as of coagulation (thrombin-antithrombin complex formation) and complement (C3a, C5a generation) was observed. Under the experimental conditions used, the optimal anticoagulation regimen was 0.5 IU heparin plus 0.375 mg citratelml blood. Priming the column with a buffer of pH 7.4 containing heparin, citrate, and Ca²⁺ is recommended. In conclusion, this new adsorber exhibited selective LDLC adsorption in vitro combined with excellent ex vivo biocompatibility and thus holds great promise for a successful clinical application in a closed-loop system in patients.     

Effect of low-dose citrate anticoagulation on the clinical safety and efficacy of direct adsorption of lipoproteins (DALI apheresis) in hypercholesterolemic patients: a prospective controlled clinical trial

Direct adsorption of lipoproteins (DALI) is the first lipid apheresis system compatible with whole blood with the advantage of a very simple procedure. A mixture of heparin plus citrate (ACD-A) is used for the anticoagulation regimen (AR). A clinical, prospective, controlled crossover study was performed to test the safety and efficacy of low-dose citrate (LDC) anticoagulation in DALI. Five chronic DALI patients suffering from coronary heart disease and hypercholesterolemia underwent 3 DALI sessions each using the LDC anticoagulation regimen (60 IU heparin/kg body weight as initial bolus; 1:40 ACD-A: blood as perfusion). This was compared to 3 sessions per patient with the standard AR (bolus of 20 IU heparin/kg, 1:20 ACD-A as perfusion). Patient blood volumes (1.6; average of 7,040 ml) were treated with 750 ml adsorber gel per session at a blood flow rate of 60 ml/min. Mean LDL and Lp(a) reductions exceeded 60% with both AR. No clinical side effects were observed. Both AR controlled the coagulation well as evidenced by a sufficient prolongation of the partial prothrombin time (PTT) and activated clotting time as well as low thrombin-antithrombin (TAT) formation. Biocompatibility parameters exhibited favorable results (low activation of complement and cells, and only slight formation of C3a, C5a, beta-thromboglobulin, elastase, and TNF-alpha). The asymptomatic bradykinin generation was comparable in both study arms. LDC optimized the ionized calcium levels and pH in the efferent blood postadsorber. LDC anticoagulation was safe and effective, and may further improve the tolerance of DALI apheresis in hypercholesterolemic patients.     

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.     

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.     

Lipid Apheresis: From a Heroic Treatment to Routine Clinical Practice

Abstract: Lipid apheresis has developed from a heroic treatment into a routine clinical therapy and currently is the major indication for performing extracorporeal plasma therapy. Whereas it was once reserved for patients with homozygous familial hypercholesterolemia, today it has a place in the secondary prevention of severe coronary heart disease when low-density lipoprotein (LDL)-cholesterol levels exceed 150 mg/dl, despite conservative treatment, in any type of primary hypercholesterolemia. Unselective plasma exchange has been replaced by a variety of selective procedures. The efficacy of the treatment can be maximized by combining LDL apheresis with the use of cholesterol synthesis enzyme inhibitors. Clinical studies have shown that drastic cholesterol reduction can result in regression of coronary atherosclerosis as well as in reduced cardiac morbidity and mortality. Technical progress comprises improved selectivity, online regeneration of adsorbers, and LDL adsorption from whole blood. Recently, a new LDL hemoper-fusion procedure was successfully tested in a clinical pilot study; blood is passed directly over a lipid sorbent without prior plasma separation. If this system is demonstrated to be safe and effective in clinical Phase III trials, a further qualitative step in the rapid development of LDL apheresis will have been made.     

Contact activation in low-density lipoprotein apheresis systems

BACKGROUND: Anaphylactoid reactions due to contact activation have been observed in patients on ACE inhibitor therapy and hemodialysis with negatively charged dialysis membranes. Negatively charged surfaces are functional constituents of different LDL apheresis systems. Therefore, contact activation was investigated during LDL apheresis with three different systems: (i) heparin-induced extracorporeal LDL precipitation (HELP); (ii) dextran sulfate cellulose (DSC) columns; and (iii) modified polyacrylate gels (DALI) in a clinical setting. METHODS: 24 prevalent patients on regular LDL apheresis treatment were included in the study. Bradykinin, prekallikrein, and HMW kininogen were measured during a single LDL apheresis at different sites of the systems. RESULTS: LDL apheresis with DSC and DALI was associated with an extreme release of bradykinin after the passage of plasma or blood through the LDL adsorbers as well as with a decrease of prekallikrein and HMW kininogen during the course of the treatment. Bradykinin release exceeded the degradation capacity of the kininase II, since markedly elevated bradykinin concentrations were observed in the arterial line of the extracorporeal circuits of both systems. This was not associated with anaphylactoid reactions. In contrast to the treatments with DSC and DALI, the HELP system did not lead to any activation of the kallikrein-kinin system. CONCLUSION: From our data we conclude that angiotensin converting enzyme (ACE) inhibitors are contraindicated in patients on LDL apheresis with the DSC and the DALI system. Because the HELP system does not activate the kallikrein-kinin system, patients who need ACE inhibitors are predisposed for this LDL apheresis procedure.     

Particle release in extracorporeal low-density lipoprotein lowering therapies

Release of microparticles into the blood during extracorporeal circulation must be kept low because of possibly serious acute and chronic adverse effects. Concentration and size distribution of microparticles were measured during simulated treatments (n = 7) on original equipment for 2 standard low-density lipoprotein (LDL) elimination procedures (DALI 750, Fresenius AG, St. Wendel, Germany and Liposorber, Kaneka Corporation, Osaka, Japan) and compared to hemofiltration solutions. For both systems as well as in hemofiltration solutions, the mean particle concentrations in 500 ml portions gathered from the efferent blood line stayed below 10% of pharmacopoeia standards for infusion solutions (United States Pharmacopoeia, European Pharmacopoeia) in all measured size classes. Although particle concentrations were comparable in all systems, the mean total number of particles > or =2 microm released per session was lowest in the DALI (167,000) compared to the Liposorber (465,000) and hemofiltration solutions (2,240,000). This was mainly due to different total processed blood volumes necessary to achieve the required LDL reduction.     

Activity of Free Radical Scavenging Enzymes in Red Cells and Plasma of Patients Undergoing Extracorporeal Low-Density Lipoprotein Apheresis

There is evidence that reactive oxygen species (ROSs) are generated in extracorporeal circuits. Free radical scavenging enzymes (FRSEs) such as glutathione reductase (GSSG-R), glutathione peroxidase (GSH-Px), and superoxide dismutase (SOD) protect against the damaging effect of ROSs. The influence of extracorporeal treatment on FRSE activity was investigated in the plasma and red blood cells (RBCs) of 21 patients undergoing regular low-density lipoprotein (LDL) apheresis. The FRSEs GSSG-R, GSH-Px, and SOD were measured. Determinations were made before and after a single treatment. Because all apheresis patients suffered from coronary heart disease (CHD), 201 CHD patients and 90 individuals without CHD, neither group undergoing apheresis, served as controls. In apheresis patients, GSH-Px (33.9 ± 8.2 U/g Hb) and GSSG-R (7.6 ± 0.9 U/g Hb) activities were increased whereas SOD activity (5.4 ± 1.5 U/g Hb) was decreased in RBCs before a single treatment compared to controls. Plasma FRSEs of apheresis patients were not different from those of controls. There was no effect of a single treatment on FRSEs in RBCs. However, a significant decrease in plasma GSH-Px activity (209.9 ± 24.9 U/ml) due to the extracorporeal treatment was observed. These data show that long-term extracorporeal therapy with LDL apheresis modulates the activity of antioxidant enzymes in RBCs whereas a single treatment was without major effect on FRSE activity in RBCs and plasma, except for plasma GSH-Px.     

Low-density lipoprotein oxidation is increased in kidney transplant recipients

Abstract  Oxidative modification of low-density lipoproteins (LDL) plays an important role in the pathogenesis of atherosclerosis. In addition, there is evidence that chronic vascular allograft rejection may be mediated by oxidised LDL. Plasma lipoprotein concentrations and parameters of LDL oxidation were determined in 19 kidney transplant recipients and 19 healthy controls. Plasma triglycerides and total cholesterol was significantly higher in patients than in the controls. The mean LDL diameter was smaller in patients than in the controls (23.6 ± 0.71 nm vs 27.78 ± 1.16 nm, P < 0.002). Furthermore, the lag time of copper-induced in vitro LDL oxidation was shorter in patients than in the controls (101 ± 23 min vs 148 ± 81 min, P = 0.02). The titre and concentration of both IgG and IgM autoantibodies against mal-ondialdehyde-modified LDL (MDA-LDL) were higher in the patients. We conclude that there is in vitro and in vivo evidence of increased LDL oxidation in renal transplant recipients. This might facilitate the progression of atherosclerosis and enhance the process of chronic vascular rejection.     

Modified DALI LDL-apheresis using trisodium citrate anticoagulation plus bicarbonate or lactate-buffered hemofiltration substitution fluids as primers

BACKGROUND: DALI (direct adsorption of lipids) is the first LDL-apheresis technique able to adsorb low-density lipoprotein (LDL) and lipoproteina) directly from whole blood. In the standard procedure, acid citrate dextrose (ACD-A) is used as anticoagulation and the adsorber is rinsed with a specially manufactured priming solution (PS). Using neutral trisodium citrate (TSC) instead of ACD-A might improve the acid-base homeostasis during DALI apheresis; moreover, applying wholesale hemofiltration solutions instead of the special PS might avoid the use of two separate solutions for both priming before and reinfusion after the treatment, thus simplifiying the procedure. AIM: The present study was performed to test the effect of neutral (TSC) anticoagulation and of two different commercially available hemofiltration (HF) priming solutions on the efficacy and biocompatibility of DALI apheresis. MATERIALS AND METHODS: Five hypercholesterolemic chronic DALI patients were treated prospectively, on a weekly or biweekly basis, 3 times each by standard DALI-apheresis (A). by DALI using 4% TSC and bicarbonate-buffered HF BIC35-210 priming (B). as well as by DALI using 4% TSC and lactate-buffered HF 23 priming (C). After the sessions, the extracorporeal circuit (ECC) was rinsed with saline in study arm A and with the corresponding HF solutions in study arms B and C, respectively. RESULTS: Acute LDL-cholesterol reductions in the study arms A/B/C averaged 64/64/63%, for Lp(a) 62/64/62%, respectively (n=15). Clinically, all sessions were essentially uneventful and no clots were observed in the ECC. No major differences were found between the 3 study arms with respect to biocompatibility (elastase, C3a, thrombin-antithrombin, beta-thromboglobulin, bradykinin). CONCLUSION: DALI apheresis using TSC anticoagulation and HF solutions for both priming and reinfusion proved to be as safe and effective as the standard DALI apheresis. These modifications, however, further simplify the procedure.     

Lipoprotein(a) levels in relation to albumin concentration in childhood nephrotic syndrome.

BACKGROUND: Lipoprotein(a) [Lp(a)] is a lipoprotein consisting of a low-density lipoprotein (LDL) particle linked to a polymorphic glycoprotein, apoprotein(a) [apo(a)]. Prior studies have reported high Lp(a) levels in the nephrotic syndrome, but it is still controversial whether this is due to the degree of hypoalbuminemia or proteinuria. METHODS: To investigate a model of nephrotic syndrome in the absence of renal failure, we studied a group of 84 children in different clinical stages of the disease for a period of five years. We evaluated the direct relationships between lipoproteins, including Lp(a), and/or plasma albumin and proteinuria. RESULTS: Lp(a) levels were significantly higher in the subjects with the active disease compared with patients in remission, and were also significantly different when subjects were ranked by albumin quartiles. Multiple regression analysis revealed that Lp(a) levels were inversely correlated with apo(a) isoform size and plasma albumin levels but not with the proteinuria/creatinine clearance ratio. Among subjects in complete remission, Lp(a) levels were different in patients with albumin levels below or above the fifth percentile. After the improvement of the clinical stage of the disease, the Delta% variation of albumin levels was related to the Delta% of apoB and LDL cholesterol (LDL-C), but not with the Delta% variation of Lp(a), whereas the Delta% variation of LDL-C was, in turn, related to the Delta% of Lp(a) levels. CONCLUSIONS: These results suggest that in the childhood nephrotic syndrome, the increased Lp(a) levels are mainly related to hypoalbuminemia, probably through a mechanism involving apoB overproduction, which leads to an increased number of LDL particles to be converted into Lp(a).     

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.     

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.     

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.     

Low-density lipoprotein apheresis: clinical results with different methods

In 40 patients (22 women, 18 men) suffering from familial hypercholesterolemia resistant to diet and lipid lowering drugs, low-density lipoprotein (LDL) apheresis was performed over 84.9 +/- 43.2 months. Four different systems (Liposorber, 28 of 40, Kaneka, Osaka, Japan; Therasorb, 6 of 40, Baxter, Munich, Germany; Lipopak, 2 of 40, Pocard, Moscow, Russia; and Dali, 4 of 40, Fresenius, St. Wendel, Germany) were used. With all methods, average reductions of 50.6% for total cholesterol, 52.2% for LDL, 64.3% for lipoprotein (a) (Lp[a]), and 43.1% for triglycerides, and an average increase of 10.3% for high-density lipoprotein (HDL) were reached. Severe side effects such as shock or allergic reactions were very rare (0.5%) in all methods. In the course of treatment, an improvement in general well being and increased performance were experienced by 39 of 40 patients. Assessing the different apheresis systems used, at the end of the trial, there were no significant differences with respect to the clinical outcome experienced with the patients' total cholesterol, LDL, HDL, and triglyceride concentrations. However, to reduce high Lp(a) levels, the immunoadsorption method with special Lp(a) columns (Lipopak) seems to be most effective: -59% versus -25% (Kaneka) - (Baxter), and -29% (Dali). The present data 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.