Low density lipoprotein apheresis by membrane differential filtration (cascade filtration).

Membrane differential filtration (MDF) is an apheresis technique with which atherogenic lipoproteins can be eliminated from plasma on the basis of particle size. In 52 patients (REMUKAST Study, 1,702 treatments), low density lipoprotein (LDL) cholesterol was decreased by 61%, high density lipoprotein (HDL) cholesterol by 42%, and fibrinogen by 54%. Our own results in 3 patients show decreases of 62%, 31%, and 59%, respectively; lipoprotein (a) (Lp[a]) was reduced by 58%. The elimination of atherogenic lipoproteins was accompanied by a loss of macromolecules (IgM: 55%, IgG: 27%, alpha 2-macroglobulin: 49%) resulting in improved hemorrheologic parameters. Although HDL is eliminated with each apheresis session, pretreatment concentrations of HDL cholesterol increased by 24% during regular apheresis for 1 year (26 patients, REMUKAST Study). However, preapheresis concentrations of other macroglobulins such as immunoglobulins remained decreased compared to concentrations obtained before the first apheresis session (IgM: 34%, IgG: 23%, and IgA: 16%). We conclude that MDF apheresis is an effective method to lower elevated concentrations of atherogenic lipoproteins. The concomitant loss of other macromolecules transiently improves hemorrheology but demands a close monitoring of immunoglobulin concentrations as a safety parameter.     

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.     

Low density lipoprotein hemoperfusion by direct adsorption of lipoproteins from whole blood (DALI apheresis): clinical experience from a single center.

The elimination of low density lipoprotein (LDL) and lipoprotein (a) (Lp[a]) by conventional LDL apheresis techniques can only be achieved in a cell-free medium and thus requires the initial separation of plasma from the blood cells. The present paper describes the first LDL hemoperfusion system which is able to adsorb LDL and Lp(a) directly from whole blood. This simplifies the procedure substantially. The adsorber consists of polyacrylate ligands linked to a modified polyacrylamide matrix. These negatively charged polyacrylate ligands interact with the positively charged apoprotein B moiety of LDL and Lp(a), which results in selective adsorption of these lipoproteins onto the column. Three hypercholesterolemic patients suffering from overt atherosclerotic complications were treated weekly by direct adsorption of lipoproteins (DALI) (n = 20 sessions each). All patients were on the highest tolerated dose of cholesterol synthesis enzyme (CSE) inhibitors. About 1.3 patient blood volumes were treated per session. The anticoagulation was performed with acid citrate dextrose (ACD-A). The following acute reductions were achieved: LDL: 66%; Lp(a): 63%; and triglycerides: 29%. High density lipoprotein (HDL) (-13%) and fibrinogen (-16%) were not substantially reduced. The sessions were essentially uneventful. Due to a low ACD-A infusion rate, no hypocalcemic episodes were registered. One patient on enalapril was treated without complications when this angiotensin converting enzyme (ACE) inhibitor was withdrawn 2 days prior to apheresis. In summary, in our hands, DALI apheresis proved to be a simple, safe, and efficient method of lipid apheresis in hypercholesterolemic patients refractory to conservative lipid lowering therapy.     

Hyperlipoprotein(a)aemia in nephrotic syndrome

The nephrotic syndrome is frequently associated with hyperlipidaemia and hyperfibrinogenaemia, leading to an increased coronary and thrombotic risk, which may be enhanced by high lipoprotein (a) [Lp(a)] concentrations. We followed the quantitative and qualitative pattern of plasma lipoproteins over 18 months in a patient with nephrotic syndrome suffering from premature coronary artery disease and with elevated level of Lp(a) (470 mg dL⁻¹). Analysis of kinetic parameters after heparin-induced extracorporeal plasma apheresis revealed a reduced fractional catabolic rate for both low-density lipoprotein (LDL) and Lp(a). After improvement of the nephrotic syndrome, Lp(a) decreased to 169 mg dL⁻¹ and LDL concentrations were normalized. The decrease of Lp(a) was associated with an increase in plasma albumin concentrations. Analysis of apo(a) isoforms in the patient showed the presence of isoform S2 (alleles 10 and 19). Consequently, the authors' present strategy is to normalize the elevated Lp(a) and fibrinogen levels. For this purpose heparin-mediated extracorporeal LDL precipitation (HELP) apheresis is a promising regimen, helping to reduce the thrombotic risk and prevent coronary and graft atherosclerosis as well as the progression of glomerulosclerosis in our patient.     

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.     

Direct adsorption of low-density lipoprotein and lipoprotein(a) from whole blood: results of the first clinical long-term multicenter study using DALI apheresis

Direct adsorption of lipoproteins (DALI) is the first low-density lipoprotein (LDL)-apheresis technique by which atherogenic LDL and lipoprotein(a) (Lp(a)) can be selectively removed from whole blood without plasma separation. The present study was performed to evaluate the efficacy, selectivity and safety of long-term DALI apheresis. Sixty-three hypercholesterolemic coronary patients were treated by weekly DALI sessions. Initial LDL-cholesterol (C) plasma levels averaged 238 +/- 87 mg/dl (range 130-681 mg/dl). On average, 34 sessions (1-45) were performed processing 1.5 patient blood volumes. The primary aim was to acutely reduce LDL-C by >or=60% per session. To this end, three different adsorber sizes could be employed, i.e., DALI 500, 750, and 1000, which were used in 4, 73, and 23% of the 2156 sessions, respectively. On average, 7387 ml of blood were processed in 116 min per session. This resulted in the following mean acute changes: LDL-C 198 --> 63 mg/dl (-69%), Lp(a) 86 --> 32 mg/dl (-64%), triglycerides 185 --> 136 mg/dl (-27%). HDL-C (-11%) and fibrinogen (-15%) were not significantly influenced. The mean long-term reduction of LDL-C was 42% compared to baseline while HDL-C slightly increased in the long run (+4%). The selectivity of LDL removal was good as recoveries of albumin, immunoglobulins, and other proteins exceeded 85%. Ninety-five percent of 2156 sessions were completely uneventful. The most frequent adverse effects were hypotension (1.2% of sessions) and paresthesia (1.1%), which were probably due to citrate anticoagulation. Access problems had to be overcome in 1.5%, adsorber and hardware problems in 0.5% of the sessions. In this multicenter long-term study, DALI apheresis proved to be an efficient, safe, and easy procedure for extracorporeal LDL and Lp(a) elimination.     

Treatment of hypercholesterolemia with heparin-induced extracorporeal low-density lipoprotein precipitation (HELP)

Familial hypercholesterolemia (FH) can cause early disability and death from premature atherosclerotic cardiovascular disease. Patients homozygous for the disease have very high plasma cholesterol, extensive xanthomatosis, and die from atherosclerosis in childhood or early adulthood. Past attempts to improve the prognosis included removal of cholesterol from the circulation by ileal bypass or biliary diversion. Neither treatment was successful. Direct removal by plasmapheresis of low-density lipoprotein (LDL), the primary carrier of cholesterol in plasma, was first performed on an FH homozygous patient in 1966. The treatment was well tolerated and led to rapid diminution of xanthomas. Other experimental treatments included selective LDL apheresis with monoclonal or polyclonal antibody affinity columns. A method for selective LDL apheresis was developed in 1983 by Armstrong, Seidel, and colleagues based on heparin precipitation of LDL at low pH. This method, called HELP, removes all apolipoprotein B-containing lipoproteins including LDL and lipoprotein (a), as well as some fibrinogen. LDL apheresis by HELP is well tolerated; the incidence of side effects is low, and the treatment has been associated with regression of cardiovascular disease. LDL apheresis, rather than liver transplantation, is the treatment of choice for patients with severe, life-threatening hypercholesterolemia which does not respond to diet and drug therapy. © 1996 Wiley-Liss, Inc.     

Effect of heparin-induced extracorporeal low-density lipoprotein precipitation (HELP) apheresis on hepatitis C plasma virus load.

Association of the hepatitis C virus (HCV) with apolipoprotein B containing lipoproteins has been suggested, and this led to the concept that the low-density lipoprotein (LDL) receptor may also serve as a candidate receptor for HCV uptake into the liver. We have investigated whether heparin-induced extracorporeal LDL precipitation (HELP) LDL apheresis treatment reduces HCV plasma load in 6 patients, all infected for more than 4 years with HCV and resistant against established anti-HCV therapy. HELP apheresis treatment caused an HCV-RNA decrease of 77.3% in mean. This decline was not correlated with LDL-cholesterol reduction. HCV-RNA was retained on the HELP filter as shown for 1 patient. The effect of RNA lowering was only transient due to the high turnover of HCV. However, HELP apheresis may open a window of opportunity for an immune-modulating and antiviral therapy in the interval between two apheresis procedures in patients with high virus load.     

Evidence for maximal treatment of atherosclerosis: drastic reduction of cholesterol and fibrinogen restores vascular homeostasis.

This article summarizes the clinical and biochemical evidence for maximal treatment of atherosclerosis by a simultaneous 60% to 70% reduction of plasma low-density lipoprotein cholesterol (LDL cholesterol), fibrinogen, and lipoprotein a concentrations with heparin-mediated extracorporeal LDL/fibrinogen precipitation (HELP) apheresis and statins. Apheresis has proven efficient and safe in the treatment of more than 1,000 patients since 1984 and has been applied in children and adults for the treatment of homozygous and heterozygous familial hypercholesterolemia, coronary artery disease, ischemic cardiomyopathy, generalized atherosclerosis, or transplant-associated arteriosclerosis after cardiac transplantation. Simultaneous removal of the main atherogenic plasma compounds has an immediate impact on myocardial and peripheral vasomotion by increasing myocardial blood flow, coronary flow reserve, cerebral CO2-reactivity, and muscle oxygen tension. Removal of fibrinogen and cholesterol reduces plasma viscosity by 20% and erythrocyte aggregation by 60% which gives rise to applying the HELP apheresis in various microcirculatory disorders. Pilot studies on acute retinal ischemia, critical limb ischemia, and sudden hearing loss confirm this observation.     

Influence of atorvastatin versus simvastatin on fibrinogen and other hemorheological parameters in patients with severe hypercholesterolemia treated with regular low-density lipoprotein immunoadsorption apheresis.

Low-density lipoprotein (LDL) apheresis is a treatment option in patients with coronary artery disease and elevated LDL cholesterol concentrations if maximal drug therapy fails to achieve adequate LDL cholesterol reduction. This therapy is more effective when combined with strong lipid-lowering drugs, such as atorvastatin. However, conflicting data have been published concerning the effect of atorvastatin on fibrinogen concentration. Therefore, we investigated the effect of atorvastatin compared to simvastatin on fibrinogen concentration and other hemorheological parameters in patients treated by weekly LDL apheresis. Hemorheological parameters were, studied twice in 9 patients (4 female, 5 male, 54.0+/-8.9 years) with coronary artery disease treated by weekly LDL immunoadsorption, once during concomitant simvastatin therapy (40 mg daily) and once during atorvastatin therapy (40 mg daily). Fibrinogen concentration, plasma and blood viscosity at different shear rates, parameters of red cell aggregation at stasis and shear rate 3/s, and erythrocyte filterability were determined 7 days after the last LDL apheresis after each drug had been given for a minimum for 8 weeks. Fibrinogen concentration did not show any statistically significant difference during therapy with atorvastatin (3.09+/-0.36 g/L) compared to simvastatin (3.13+/-0.77 g/L). Plasma and blood viscosity as well as erythrocyte filterability were also unchanged. The increase in red cell aggregation at stasis during atorvastatin treatment (5.82+/-1.00 U versus 4.89+/-0.48 U during simvastatin; p < 0.05) was inversely correlated with a lower high-density liprotein (HDL) cholesterol concentration (1.17+/-0.21 mmol/L versus 1.31+/-0.30 mmol/L during simvastatin; p < 0.05). LDL cholesterol showed a strong trend to lower concentrations during atorvastatin (4.14+/-0.61 mmol/L versus 4.56+/-0.66 mmol/L during simvastatin; p = 0.07), despite a reduced plasma volume treated (3,547+/-1,239 ml during atorvastatin versus 3,888+/-1,206 mL during simvastatin; p < 0.05). In conclusion, fibrinogen concentration and other hemorheological parameters were unchanged during atorvastatin compared to simvastatin therapy with the exception of a higher red cell aggregation at stasis. Therefore, with respect to hemorheology, we conclude that atorvastatin should not be withheld from hypercholesterolemic patients regularly treated with LDL immunoadsorption.     

The familial hypercholesterolemia regression study: a randomized comparison of therapeutic reduction of both low-density lipoprotein and lipoprotein(a) versus low-density lipoprotein alone.

Lipoprotein (a) [Lp (a)] is a risk factor for coronary heart disease (CHD), especially in the presence of a raised low-density lipoprotein (LDL)-cholesterol (LDL-C). To ascertain whether reduction of both LDL and Lp(a) is more advantageous than reduction of LDL alone, patients with heterozygous FH and CHD were selected randomly to receive either LDL apheresis fortnightly plus simvastatin 40 mg/day or colestipol 20 g plus simvastatin 40 mg/day. Quantitative coronary angiography was undertaken before and after 2.1 years. Changes in serum lipids were similar in both groups except for the greater reduction of LDL-C and Lp(a) by apheresis. There were no significant differences in primary angiographic endpoints, and none of the angiographic changes correlated with Lp(a). Although LDL apheresis plus simvastatin was more effective than colestipol plus simvastatin in reducing LDL-C and Lp(a), it was not more beneficial in influencing coronary atherosclerosis. Decreasing Lp(a) seems unnecessary if LDL-C is reduced below 130 mg/dl.     

High-efficiency DALI apheresis using 1,250 ml adsorbers in a hypercholesterolemic obese patient: a case report.

Direct adsorption of lipoproteins (DALI) apheresis is the first method for direct adsorption of lipoproteins from whole blood and is therefore an easy and rapid procedure. The majority of patients reaches >60% acute low-density lipoprotein cholesterol (LDL-C) reduction using either the DALI 750 or 1000 configuration. However, in patients with extremely high LDL-C levels or very large blood volumes, these configurations may lead to suboptimal results. The current study was performed to test the safety and efficacy of DALI 1250. In a severely obese patient (185 cm, 133 kg, blood volume 7.2 L, LDL-C 239 mg/dl), 11 L of blood (1.53-fold patient blood volume) was processed at a flow rate of 80 ml/min in 2.5 h; a combined heparin-plus-citrate anticoagulation regimen was used. Commercially available DALI 1250 and DALI hardware and disposables were manufactured by Fresenius HemoCare Adsorber Technology, St. Wendel, Germany. Twenty weekly sessions were performed. Clinically and technically, the apheresis sessions were completely uneventful. As compared to DALI 1000 (n = 4 sessions), the reduction rates by DALI 1250 (n = 20) improved for LDL-C (from 52% to 66%), lipoprotein (a) (Lp[a]) (53% vs. 66%), and fibrinogen (11% vs. 16%). There was a slight increase in high-density lipoprotein cholesterol (HDL-C) loss (20% vs. 24%). Moreover, the absolute amount of LDL-C removed per session increased from 5.06 g to 5.94 g. Laboratory safety parameters remained within the normal range, the anticoagulation was well controlled, and the pressure gradients over the adsorber remained constant. In this case report, DALI 1250 was perfectly safe and significantly increased the efficacy of LDL-C and Lp(a) elimination compared to standard DALI. Thus, this high-efficiency version of DALI may be used in patients with extremely high LDL-C levels and/or large blood volumes.     

Heparin-Induced extracorporeal low-density lipoprotein precipitation apheresis: a new therapeutic concept in the treatment of sudden hearing loss.

Vascular events, immunological processes, and viral infections have to be considered as pathomechanisms for most cases of sudden hearing loss (SHL). In order to clarify predisposing conditions for vascular events. hemorheological parameters have been studied in 53 patients suffering from SHL within 5 days of onset, along with a control group. The striking result was a significantly elevated level of plasma fibrinogen leading to a significantly increased erythrocyte aggregation and plasma viscosity. No significant difference could be found in all other parameters of clinical chemistry, hematology, and hemostasis. These results encouraged us to use heparin-induced extracorporeal low-density lipoprotein (LDL) precipitation (HELP) apheresis, which acutely and drastically reduces LDL. fibrinogen, and lipoprotein (a) in the treatment of patients suffering from sudden hearing loss and hyperfibrinogenemia or hypercholesterolemia. In a pilot study including 30 patients, we found a better recovery of hearing in the patients treated with a single HELP apheresis when compared to conventional treatment for 10 days with prednisolone and dextranes. Currently, we verify these results in a larger multicenter trial in patients regardless of their fibrinogen or LDL levels. In the future, there will be different specific treatments of sudden hearing loss based on the different pathomechanisms. The clinical impression and first controlled data make it likely that HELP apheresis is useful in the therapy of sudden hearing loss with suspected vascular origin.     

Improvement of hemorheology by DALI apheresis: acute effects on plasma viscosity and erythrocyte aggregation in hypercholesterolemic patients.

Plasma viscosity (PV) and erythrocyte aggregation (EA) are determinants of microcirculation, especially under the compromised hemodynamic conditions resulting from atherosclerosis. Direct adsorption of lipoproteins (DALI) apheresis is the first method for direct adsorption of lipoproteins; it drastically reduces low-density lipoprotein (LDL)-cholesterol and lipoprotein (a) (Lp[a]), and may therefore improve PV and EA. The current study was performed to test the effect of DALI on hemorheology. Six hypercholesterolemic patients who had been on regular LDL apheresis for at least several months were treated on a weekly or biweekly basis, on average 5 times each by DALI. Before and after each session, PV was measured by a capillary tube plasma viscosimeter and EA by rotational aggregometry. Single DALI sessions (n = 31) acutely decreased PV from 1.18 +/- 0.04 to 1.06 +/- 0.3 mPa (-10%) while EA improved from 22.8 +/- 4.4 to 13.3 +/- 4.5 (arbitrary units) (-42%). LDL-cholesterol, Lp(a), and very-low-density lipoprotein (VLDL)-cholesterol were effectively reduced while the decrease of triglycerides and fibrinogen was only moderate. DALI apheresis exerted an acute positive effect on blood hemorheology which may have beneficial effects on microcirculation. This hypothesis is in accordance with the clinical observation that in some patients, improvement of angina and/or exercise tolerance can be observed after only a few DALI sessions where changes of coronary stenoses cannot be expected yet.     

Clinical application and effectiveness of low-density lipoprotein apheresis in the treatment of coronary artery disease.

The Low-Density Lipoprotein Apheresis Coronary Atherosclerosis Prospective Study (L-CAPS) examined whether or not combined low-density lipoprotein (LDL) apheresis and drug therapy apheresis could induce the regression of coronary atherosclerotic lesions in patients with familial hypercholesterolemia. Twenty-eight patients treated with LDL apheresis and drugs and 11 patients treated with drugs alone underwent sequential coronary angiography 2.5 years apart. The frequency of cases with regression or no change was significantly higher for the apheresis group than for the control group (p = 0.004). The LDL apheresis Angioplasty Restenosis Trial (LART) investigated the hypothesis that high plasma lipoprotein (a) (Lp[a]) levels were associated with increased incidences of restenosis after coronary angioplasty. Two days before and 5 days after angioplasty, 66 patients underwent LDL apheresis. The restenosis rates were 21% in the 42 patients whose Lp(a) levels were reduced > or = 50% and 50% in the 24 patients whose Lp(a) levels were reduced < 50% (p < 0.05). LDL apheresis is effective in the prevention of the progression of coronary atherosclerosis. Its potential application in restenosis prevention should be further investigated.     

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.     

Prospective cross-over comparisons of three low-density lipoprotein (LDL)-apheresis methods in patients with familial hypercholesterolaemia

We prospectively compared effectiveness, selectivity and biocompatibility of three LDL-apheresis methods, immunoadsorption (IMAL), dextran sulphate adsorption (DSAL) and heparin-induced extracorporeal LDL precipitation (HELP). Seven patients with familial hypercholesterolaemia were treated twice with each method in random sequence. Reduction in atherogenic lipoproteins was without significant difference: LDL −60% to −75%, VLDL −20% to −30%, triglycerides −20% to −42%. High-density lipoprotein (HDL)-cholesterol was reduced by IMAL only (−27%, P <0.05); DSAL and HELP did not decrease HDL. Total plasma protein reduction was 13–15% with each method, indicating unselectivity. Albumin was significantly decreased by IMAL (−15%, P <0.05) but not by the other methods. DSAL and HELP reduced fibrinogen (−40%, −58%, P <0.0001) and other clotting factors. IMAL had almost no effect on coagulation. The white blood cell count did not change. C3 and C4 complement were decreased (−20% to −46%) by all methods. C5a complement did not increase in systemic blood, but was increased in the extracorporeal circulation of IMAL (+200%) and HELP (+150%). Plasma PMN elastase rose in all methods (+200%) indicating neutrophile degranulation. In conclusion, in this short-term study of a small patient population, effectiveness of the three LDL-apheresis methods was similar, but selectivity and biocompatibility were different. The therapeutic relevance of these differences for long-term treatment remains to be elucidated.     

Low-density lipoprotein-apheresis in two patients with extremely elevated lipoprotein (a) levels

Two male caucasian patients (36 and 42 years old) with heterozygous familial hypercholesterolemia and extremely elevated lipoprotein Lp(a) concentrations, resistant to diet and lipid-lowering drugs, were treated with low-density lipoprotein (LDL)-apheresis for 55 months (liposorber system, Kaneka®, Japan) and 15 months (immunoadsorption system, special Lp(a) columns. Lipopak®, Pocard, Russia). Lp(a) dropped on average by 50%, total cholesterol by 27%, LDL-cholesterol by 42%, triglycerides by 43%, and the fibrinogen concentration by 16%. © 1996 Wiley-Liss, Inc.     

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.     

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.