Extracorporeal treatment of hypercholesterolaemia

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

An Effective LDL Removal Filter for the Treatment of Hyperlipidemia

Abstract: On-line membrane plasma fractionation techniques have made semiselective removal of pathological macromolecules practical. However, several problems such as cryogel formation exist when the procedure is performed at ambient temperature. Cryogel formation takes place when heparinized plasma is cooled below 35°C and when it tends to occlude the pore structure of the secondary filter membrane resulting in a poor molecular cut off of the macromolecular filter. Thermofiltration is one of the on-line plasma fractionation techniques used when warming plasma from 37 to 42°C to prevent cryogel formation. Thermofiltration enhanced the performance of the lipofilter (Kuraray 4A) and demonstrated better molecular cut off between low density lipoprotein (LDL) cholesterol and high density lipoprotein (HDL) cholesterol than double filtration plasmapheresis (DFPP). An improved lipofilter (Kuraray 5A) has been developed and has shown better molecular cut off between LDL cholesterol and HDL cholesterol than the 4A filter. However, cryogel formation still occurred even using the 5A filter during the DFPP procedure. Thermofiltration maintains the performance of the secondary filter by preventing cryogel formation. Further studies are required to evaluate the enhanced performance of the 5 A filter by thermofiltration.     

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.     

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

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

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.     

Development of Selective Low-Density Lipoprotein (LDL) Apheresis System: Immobilized Polyanion as LDL-Specific Adsorption for LDL Apheresis System

Abstract: Low-density lipoprotein (LDL) is widely recognized as one of the major risk factors for developing coronary heart diseases. Despite intensive development of LDL-lowering drugs, there still exist those patients with refractory hyperlipidemia whose plasma LDL levels are not sufficiently lowered by drugs. LDL apheresis, direct removal of plasma LDL from circulating blood, is thought to be the most promising treatment for such refractory patients. Various techniques, such as the use of an im-munoadsorbent utilizing an anti-LDL antibody, have been used in an attempt to achieve the selective removal of LDL. However, none were widely used because of complications, poor selectivity, and so forth. To establish a safe and effective LDL apheresis system, we chose a synthetic affinity adsorbent as the LDL-removing device. Synthetic polyanion compounds were used as the affinity ligands for LDL adsorbent to simulate the anion-rich sequence of LDL binding sites in the human LDL receptor. Among various polyanion compounds, those polyanions with sulfate or sulfonate groups and hydrophilic backbone were found to have strong affinity for LDL. In contrast, polyanions with carboxyl groups showed poor affinity. Dextran sulfate (DS) was selected as the affinity ligand of LDL adsorbent for its high affinity and low toxicity. The influence of its charge density and molecular weight on its affinity for LDL was suitable. The affinity rapidly increased as the charge density increased, then, reached a constant value. Little affinity was found for either the DS monomer (glucose sulfate) or DS with a molecular weight higher than 10⁴ daltons whereas DS with molecular weights in the midrange showed strong affinity. DS with a midrange molecular weight was immobilized on cellulose hard gel to give LDL adsorbent clinical application. The adsorbent demonstrated an excellent selectivity for LDL and very low density lipoprotein (VLDL) in vitro. Adsorption of high-density lipoprotein and major plasma proteins was almost negligible. Additional study of the LDL-binding mechanism revealed that DS directly interacts with positively charged sites on LDL, which demonstrates that the nature of the interaction is the same as that of LDL receptor. An LDL adsorption column (Liposorber) packed with an LDL adsorbent and polysulfone hollow-fiber plasma separator (Sulflux) was developed as an efficient LDL apheresis system. Clinical investigation proved that this system is capable of intensively lowering the plasma LDL level without affecting major plasma components.     

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

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

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     

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.     

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.     

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

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

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

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

Extracorporeal Removal of Lipids by Dextran Sulfate Cellulose Adsorption

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

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

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

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

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

Low-density lipoprotein apheresis: 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.     

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

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

Therapeutic Apheresis of Immune Diseases in Nephrology Department

Objective. The clinical efficacy of therapeutic apheresis is still controversial. We undertook a retrospective review of apheresis treatment to ascertain its safety and efficacy. Methods. We reviewed 31 patients (13 male, 18 female). Plasmapheresis was performed on 7 patients with hematologic disorders, 5 patients with neurologic disorders, 6 patients with systemic diseases, and 3 patients with Lyell syndrome. Immunoadsorption onto protein A sepharose was evaluated as rescue therapy in 7 patients. Low‐density lipoprotein (LDL) apheresis was performed on 3 patients. Results. There were five mortalities due to serious complications of their primary disease. Most complications were mild such as hypotension and hypocalcemia. Two patients who received LDL apheresis had severe anaphylactic reactions. Apheresis was effective in the remaining 24 patients. Conclusions. The therapeutic apheresis consists of a continuously improving therapeutic method for diseases with high mortality and morbidity, especially in cases with poor outcome by using current medications.     

Effect of Nafamostat Mesilate on Bradykinin Generation and Hemodynamics During LDL Apheresis

Abstract: Dextran-sulfate (DS) cellulose used for low-density lipoprotein (LDL) apheresis seems to be a weak activator of the contact phase of the intrinsic coagulation pathway because the surface of this substance has negative charges. Heparin, a commonly used anticoagulant, has no effect on this process whereas the process is inhibited by a newly developed anticoagulant, nafamostat mesilate (NM). The effects on bradykinin generation were compared between heparin and NM. Five patients with severe hypercholesterolemia were treated with LDL apheresis using either heparin or NM on a different day. During apheresis with heparin, factor XII, high molecular weight kininogen, and prekallikrein were markedly decreased by passing through the DS column. A distinct generation of bradykinin was observed by passing plasma through the DS column, and this led to the rise of bradykinin levels from 12 ± 5 (mean ± SE) to 72 ± 14 pg/ml after treatment of 1,000 ml of plasma. NM suppressed almost completely the rise of bradykinin levels. Although blood pressure was apt to decrease during apheresis with heparin, there was no significant difference in blood pressure between heparin and NM. Since an angiotensin-converting enzyme inhibitor may lead to a marked rise in blood levels of bradykinin by suppressing its degradation, the use of NM is recommended for apheresis in patients taking this drug.     

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.