DALI Low‐Density Lipoprotein Apheresis in Homozygous and Heterozygous Familial Hypercholesterolemic Patients Using Low‐Dose Citrate Anticoagulation

Abstract: The purpose of this study was to clarify the efficacy and safety of direct adsorption of lipoprotein low‐density lipoprotein apheresis (DALI LDL apheresis) in patients with severe homozygous and heterozygous familial hypercholesterolemia who showed minor adverse effects during treatment with the usual DALI configuration (AC 1:20) through the use of a new system with low‐dose citrate anticoagulation (AC 1:40) developed in order to minimize citrate‐related adverse effects. Serum total cholesterol and LDL‐cholesterol (LDL‐C) showed a decrease of 57% to 61%, and 62 % to 67%, respectively, in the 2 patients. Serum lipoprotein (a) (Lp[a]) was higher in the homozygous patient (Patient 1: MD) and within the normal range in the heterozygous patient (Patient 2: ES). In the former, Lp(a) was reduced by 52%. Serum high‐density lipoprotein cholesterol (HDL‐C) showed a statistically insignificant acute reduction: 15% to 19%. The observed reduction is mainly related to the well‐known effect of hemodilution. The cardiovascular risk (total cholesterol/HDL‐C) was reduced in both patients (46% to 54%) as expected. Serum triglycerides were reduced by 33% to 49%. The mean blood volume processed per session was 7,600 ml. Fifteen treatments for each patient have successfully been completed without the appearance of any clinically significant subjective and objective symptoms related to treatment with the new system.     

First Steps Toward the Establishment of a German Low‐Density Lipoprotein‐Apheresis Registry: Recommendations for the Indication and for Quality Management

Abstract: New recommendations for the indication of treatment with selective extracorporeal plasma therapy low‐density lipoprotein apheresis (LDL‐apheresis) in the prevention of coronary heart disease are urgently needed. The following points are the first results of the ongoing discussion process for indications for LDL‐apheresis in Germany: all patients with homozygous familial hypercholesterolemia with functional or genetically determined lack or dysfunction of LDL receptors and plasma LDL cholesterol levels >13.0 mmol/L (>500 mg/dL); patients with coronary heart disease (CHD) documented by clinical symptoms and imaging procedures in which over a period of at least 3 months the plasma LDL cholesterol levels cannot be lowered below 3.3 mmol/L (130 mg/dL) by a generally accepted, maximal drug‐induced and documented therapy in combination with a cholesterol‐lowering diet; and patients with progression of their CHD documented by clinical symptoms and imaging procedures and repeated plasma Lp(a) levels >60 mg/dL, even if the plasma LDL cholesterol levels are lower than 3.3 mmol/L (130 mg/dL). Respective goals for LDL cholesterol concentrations for high‐risk patients have been recently defined by various international societies. To safely put into practice the recommendations for LDL‐apheresis previously mentioned, standardized treatment guidelines for LDL‐apheresis need to be established in Germany that should be supervised by an appropriate registry.     

Acute Changes in Plasma Levels of Hepatocyte Growth Factor During Low‐Density Lipoprotein Apheresis

Abstract: Hepatocyte growth factor (HGF) is a mesenchyme‐derived pleiotropic factor, and angiogenesis is included in a variety of its functional effects. HGF levels were measured in 5 sessions of low‐density lipoprotein (LDL) apheresis in 3 patients with severe hypercholesterolemia. Blood was collected at the start (T0) and at 1,000 ml (T1), 2,000 ml (T2), and 3,000 ml (T3) plasma treatments. During LDL apheresis, HGF levels increased from 1.59 ± 0.78 (mean ± SE, n = 5) ng/ml at T0 to 6.64 ± 0.97 at T1, 6.28 ± 0.97 at T2, and 5.20 ± 0.94 at T3. In one apheresis session, HGF increased immediately at the 100 ml plasma treatment stage. HGF was adsorbed completely by a dextran‐sulfate (DS) column. Despite the adsorption by the DS column, HGF in the patient blood increased to the levels with functional effects. The improvement of ischemic symptoms due to LDL apheresis may be related to the angiogenic activities of HGF.     

Effects of Low‐Density Lipoprotein Apheresis on Coronary and Carotid Atherosclerosis and Diabetic Scleredema in Patients with Severe Hypercholesterolemia

Abstract: Correlations between serum cholesterol levels and progression of coronary and peripheral atherosclerosis have been found in many recent studies. It has also been demonstrated that aggressive cholesterol‐lowering therapy with low‐density lipoprotein (LDL) apheresis, a method of LDL elimination by extracorporeal circulation, is effective not only for coronary artery disease, but also for systemic circulatory disturbance in severe hypercholesterolemic patients with familial hypercholesterolemia (FH) in particular. We found that LDL apheresis treatment with medical therapy improved coronary atherosclerotic lesions, based on coronary angiography evaluation and histopathological observation, suppressed progression of early carotid atherosclerotic lesions on annual B‐mode ultrasonography, and improved diabetic scleredema in FH patients. This effectiveness of LDL apheresis appears to be due to recovery of vascular endothelial function and improvement of blood rheology. For diseases that are possibly due to circulation disturbance and that are intractable with drugs alone, LDL apheresis may be worth trying, particularly for patients complicated by hyperlipemia.     

Effects of Direct Adsorption of Lipoproteins Apheresis on Lipoproteins,Low‐Density Lipoprotein Subtypes,and Hemorheology in Hypercholesterolemic Patients with Coronary Artery Disease

Abstract: Direct adsorption of lipoproteins (DALI) apheresis has been shown to reduce effectively low‐density lipoprotein (LDL) cholesterol and lipoprotein (a) concentrations. However, the effects on nontraditional risk indicators such as hemorheology and LDL subtypes have not been investigated so far. Five patients (2 women, 3 men, age 53 ± 8 years) with coronary artery disease and severe LDL hypercholesterolemia regularly treated with other LDL apheresis devices entered the study and were then treated with DALI for the first time. Hemorheological and lipoprotein parameters were measured before and immediately after the initial DALI apheresis as well as before the fourth DALI apheresis. Compared to baseline (before the first DALI apheresis), the following parameters were significantly improved (p < 0.05) after the first DALI apheresis: LDL cholesterol (69 ± 28 versus 208 ± 82 mg/dl) and cholesterol in each LDL subfraction as well as plasma viscosity (1.23 ± 0.04 versus 1.37 ± 0.06 mPa), C‐reactive protein, native blood viscosity, red cell aggregation, and red cell deformability. When parameters before the fourth DALI apheresis were compared to baseline, LDL cholesterol was still lower, and red cell deformability was still improved while cholesterol in each subfraction showed a statistical trend to lower concentrations (0.08 < p < 0.14). In conclusion, DALI apheresis not only reduces LDL cholesterol but also induced a significant reduction of cholesterol in all LDL subfractions and improved various hemorheological parameters.     

Current Topics on Low‐Density Lipoprotein Apheresis

Abstract: 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.     

Outcome of Patients on Long Term Low‐Density Lipoprotein Apheresis with Membrane Differential Filtration: A Case Study in Three Patients 14 Years on Treatment

Abstract: Membrane differential filtration (MDF) 1 , 2 is a variety of cascade filtration. Three patients with primary hyperlipoproteinemia and coronary heart disease (2 patients with foregoing myocardial infarction) were treated with MDF for a period of 14 years. The mean treatment interval was 21 days. The basic level of low‐density lipoprotein (LDL) cholesterol was about 450 mg/dl, and the level on LDL apheresis with comedication of statins was 180 to 200 mg/dl before treatment. Atherosclerosis progressed slowly during this period, and myocardial infarctions were avoided. However, in all 3 patients angiologic interventions became necessary. MDF is a well tolerated method that can be conducted without allergic hazards. The clinical results compare with those of other apheretic techniques.     

Low Density Lipoprotein Apheresis in Treatment of Hyperlipidemia: Experience with Four Different Technologies

Abstract: The prognosis of patients suffering from severe hyperlipidaemia (HLP), sometimes combined with elevated lipoprotein (a) levels, and coronary heart disease (CHD) refractory to diet and lipid lowering drugs is poor. A new therapeutic option for such patients is regular treatment with low density lipoprotein (LDL) apheresis. In total 33 patients (16 males, 17 female, aged 43.8 ± 14.3 years), suffering from severe HLP resistant to diet and lipid lowering drugs, were treated for 62.3 ± 21.3 (range, 1–113) months with LDL‐apheresis. Four different LDL‐apheresis systems were used: the dextran sulfate adsorption for 28 of 33 (Liposorber, Kaneka, Japan), immunoadsorption for 2 of 33 (Therasorb, Baxter, Germany), LDL‐hemoperfusion for 2 of 33 (Dali, Fresenius, Germany), and the immunoadsorption system with special anti‐lipoprotein (a) columns for 1 of 33 patients (Lipopak, Pocard, Russia). Before applying LDL‐apheresis, 27 of 33 patients suffered from CHD with severe angina pectoris symptoms, a history of myocardial infarction or coronary artery venous bypass (CAVB). With LDL‐apheresis, reductions (p < 0.05) of 46% for total cholesterol, 49% for LDL, 28% 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 29 of 33 patients. In 23 of 27 patients suffering from CHD, a reduction of 60 to 100% of nitrate medication was observed. Regarding the different apheresis systems used, there were no significant differences with respect to the clinical outcome and concerning total cholesterol, LDL, HDL, and triglyceride concentrations. But, in respect to elevated lipoprotein (a) levels, the immunoadsorption method using special anti‐lipoprotein (a) columns seems to be the most effective (?57% versus ?25%[Kaneka, p < 0.05] or ?23%[Baxter, p < 0.05]). The present data clearly demonstrate that treatment with LDL‐apheresis in patients suffering from severe HLP, refractory to maximum conservative therapy, is effective and safe in long‐term application.     

Low‐Density Lipoprotein Apheresis and Changes in Plasma Components

Abstract: Several different techniques of low‐density lipoprotein (LDL) apheresis are available for management of severe hypercholesterolemia. Among them, the adsorption system with a dextran‐sulfate cellulose (DSC) column is most widely used. In addition to adsorption of LDL, DSC adsorbs plasma constituents that have the following characteristics: proteins containing apolipoprotein B (Lp[a]); proteins involved in the initial contact phase of the intrinsic coagulation pathway (coagulation factor XII, high‐molecular‐weight kininogen and prekallikrein); factors with lipophilic characteristics (coagulation factor VII, coagulation factor VIII, and vitamin E); and proteins with adhesive or other characteristics (von Willebrand factor, fibronectin, serum amyloid P component, hepatocyte growth factor). The adsorption of these proteins seems to ameliorate prevention or regression of atherosclerosis. Moreover, plasma treatment by the DSC column may be useful for treatment of inexorable diseases, such as amyloidosis. On the other hand, the DSC column generates bradykinin by activation of the initial contact phase of the intrinsic coagulation pathway. Bradykinin generation may explain the functional improvement in the circulatory system, as well as hypotension during LDL apheresis, which is observed in patients taking ACE inhibitors.     

Beneficial Effect of Aggressive Low‐Density Lipoprotein Apheresis in a Familial Hypercholesterolemic Patient with Severe Diabetic Scleredema

Abstract: We present a 59‐year‐old woman with severe diabetic scleredema (DS) associated with heterozygous familial hypercholesterolemia (FH). She had been treated with drugs to lower blood glucose, with insulin for diabetes mellitus (DM), and with low‐density lipoprotein (LDL) apheresis therapy monthly or every 2 weeks in addition to drugs to lower serum lipids for FH. However, her scleredema had not improved. After we had tried weekly LDL apheresis therapy for a period of 3 years to treat her hyperlipidemia, the levels of her serum lipids were reduced to normal ranges, and scleredema in her nape improved. We also demonstrated the histopathological improvement in dermis of her cervical skin. We conclude that weekly LDL apheresis therapy is effective for diabetic scleredema that is resistant to conventional treatments.     

State of Percutaneous Transluminal Coronary Artery Angioplasty and Effectiveness of Low‐Density Lipoprotein Apheresis

Abstract: We have recognized percutaneous transluminal coronary artery angioplasty (PTCA) as an important procedure for achieving myocardial revascularization. PTCA has been performed for stable and unstable angina, acute myocardial infarction, and silent myocardial ischemia. Among many new devices, the coronary stent is the most important advancement in PTCA. Frequent stent use is due to the introduction of antiplatelet therapy to prevent stent thrombosis. One serious problem is that PTCA, even with stent use, often causes chronic restenosis. This problem has not been solved, however, despite various strategies. Aggressive lipid‐lowering therapy is one of the most important therapies for coronary heart disease. The findings in aggressive lipid‐lowering therapy show us its importance. We report that low‐density lipoprotein (LDL) apheresis, when performed immediately before and after PTCA, can prevent restenosis of coronary artery lesions. Lipid‐lowering therapy should be applied more aggressively with medicine and/or with LDL apheresis for patients who have undergone PTCA.     

A Case of Nephrotic Syndrome Due to Lupus Nephritis Which Was Controlled with Low‐Density Lipoprotein Apheresis

Abstract: Our report discusses a 29 year old female patient with nephrotic syndrome due to lupus nephritis, biopsy‐proven World Health Organization classification Types IVb and V that was controlled with low‐density lipoprotein (LDL) apheresis. She was initially treated with steroid therapy, including methylprednisolone pulse therapy, and the serological activity of her systemic lupus erythematosus was suppressed. However, her nephrotic state, accompanied by severe hyperlipidemia, persisted despite the steroid therapy. Since we could not obtain her consent to administer immunosuppressants such as cyclophosphamide, we tried to treat her using LDL apheresis (LDL‐A). We found that her urine protein excretion, hyperlipidemia, hypoalbuminemia, and renal function improved following the initiation of LDL‐A. This suggests that LDL‐A may be an effective therapy for nephrotic syndrome due to lupus nephritis through short‐term amelioration of hyperlipidemia.     

Italian Multicenter Study on Low‐Density Lipoprotein Apheresis Working Group 2009 Survey

We present results of the second survey of the Italian Multicenter Study on Low‐Density Lipoprotein Apheresis (IMSLDLa‐WG/2). The study involved 18 centers in 2009, treating 66 males and 35 females, mean age 47 ± 18 years. Mean age for initiation of drug treatment before low‐density lipoprotein apheresis (LDLa) was 31 ± 18 years, mean age to the first LDLa was 37 ± 20 years and average duration of treatment was 9 ± 6 years. The techniques used included direct adsorption of lipids, dextran sulfate cellulose adsorption, heparin‐mediated low‐density lipoprotein (LDL) precipitation, cascade filtration, and plasma exchange. The mean treated plasma/blood volumes/session were 3127 ± 518 mL and 8666 ± 1384 mL, respectively. The average plasma volume substituted was 3500 ± 300 mL. Lipid therapy before LDLa included ezetimibe, statins, ω‐3 fatty acids and fenofibrate. Baseline mean LDL cholesterol (LDLC) levels were 386 ± 223 mg/dL. The mean before/after apheresis LDLC level decreased by 67% from 250 ± 108 mg/dL (P = 0.05 vs. baseline) to 83 ± 37 mg/dL (P = 0.001 vs. before). Baseline mean Lipoprotein(a) [Lp(a)] level was 179 ± 136 mg/dL. Mean before/after apheresis Lp(a) level decreased by 71% from 133 ± 120 mg/dL (P = 0.05 vs. baseline) to 39 ± 44 mg/dL (P = 0.001 vs. before). Major and minor side effects occurred in 27 and 62 patients, respectively. Among patients with coronary artery disease (CAD), 62.3% had coronary angiography and 50.4% coronary revascularization before LDLa. Single vessel, double vessel and triple vessel CAD occurred in 19 (30.1%), 15 (23.8%) and 29 (46%) patients, respectively. Both CAD and extra‐CAD occurred in 41.5%, 39% had hypertension, 9.9% were smokers, 9.9% consumed alcohol and 42% were physically active. Ischemic cardiovascular events were not observed in any patient over 9 ± 6 years of treatment. Two centers have also treated 34 patients (females: 17/males 17; no. sessions: 36; average plasma volume treated: 3000 mL) for sudden hearing loss (SHL). Relief of symptoms was obtained, independently of the system used (HELP; cascade‐filtration).     

Therapeutic Potential of Low‐Density Lipoprotein Apheresis in the Management of Peripheral Artery Disease in Patients With Chronic Kidney Disease

Cardiovascular disease (CVD) is a major cause of death in patients with chronic kidney disease (CKD). Patients with CKD are reported to have a significant greater risk of CVD‐associated mortality than that of the general population after stratification for age, gender, race, and the presence or absence of diabetes. CKD itself is also an independent risk factor for the development of atherosclerosis, and in particular, patients undergoing dialysis typically bear many of the risk factors for atherosclerosis, such as hypertension, dyslipidemia and disturbed calcium‐phosphate metabolism, and commonly suffer from severe atherosclerosis, including peripheral arterial disease (PAD). Low‐density lipoprotein (LDL) apheresis is a potentially valuable treatment applied to conventional therapy‐resistant hypercholesterolemic patients with coronary artery disease and PAD. Although previous and recent studies have suggested that LDL apheresis exerts beneficial effects on the peripheral circulation in dialysis patients suffering from PAD, probably through a reduction of not only serum lipids but also of inflammatory or coagulatory factors and oxidative stress, the precise molecular mechanisms underlying the long‐term effects of LDL apheresis on the improvement of the peripheral circulation remains unclear and warrants further investigation.     

Effect of Heparin‐Induced Extracorporeal Low‐Density Lipoprotein Precipitation (HELP) Apheresis on Hepatitis C Plasma Virus Load

Abstract: 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.     

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.     

Improvements in Artery Occlusion by Low‐Density Lipoprotein Apheresis in a Patient with Peripheral Arterial Disease

Abstract: Peripheral arterial disease (PAD; arteriosclerosis obliterans) shows ischemic symptoms along the peripheral arteries due to reduced blood flow, and the number of patients with PAD is increasing. Several papers have reported on the clinical effect of low‐density lipoprotein apheresis (LDL‐A) on PAD, but there has been no report so far on the improvement of total peripheral artery stenosis by LDL‐A. We report on the clinical course of a female PAD patient with intractable decubitus in her heel due to the complete occlusion of anterior tibial artery who was treated by a series of LDL‐A sessions. The complete occlusion of the anterior tibial artery improved as seen on angiography, and the decubitus in her heel also markedly improved after LDL‐A therapy. This report supports the clinical benefit of LDL‐A for the treatment of PAD.     

Proteomic Analysis of Proteins Eliminated by Low‐Density Lipoprotein Apheresis

Low‐density lipoprotein apheresis (LDL‐A) treatment has been shown to decrease serum LDL cholesterol levels and prevent cardiovascular events in homozygous patients with familial hypercholesterolemia. Recently, LDL‐A treatment has been suggested to have beneficial effects beyond the removal of LDL particles. In this study, to clarify the preventive effects of LDL‐A treatment on atherosclerosis, the waste fluid from the adsorption columns was analyzed. The waste fluid of LDL adsorption columns was analyzed by two‐dimensional electrophoresis followed by mass spectrometry. Serum concentrations of the newly identified proteins before and after LDL‐A treatment were measured by enzyme‐linked immunosorbent assay. We identified 48 kinds of proteins in the waste fluid of LDL adsorption columns, including coagulation factors, thrombogenic factors, complement factors, inflammatory factors and adhesion molecules. In addition to the proteins that were reported to be removed by LDL‐A treatment, we newly identified several proteins that have some significant roles in the development of atherosclerosis, including vitronectin and apolipoprotein C‐III (Apo C‐III). The serum levels of vitronectin and Apo C‐III decreased by 82.4% and 54.8%, respectively, after a single LDL‐A treatment. While Apo C‐III was removed with very low‐density lipoprotein (VLDL) and LDL, vitronectin was removed without association with lipoproteins. The removal of proteins observed in the waste fluid has a certain impact on their serum levels, and this may be related to the efficacy of LDL‐A treatment. Proteomic analysis of the waste fluid of LDL adsorption columns may provide a rational means of assessing the effects of LDL‐A treatment.     

Influence of Single Low‐Density Lipoprotein Apheresis on the Adhesion Molecules Soluble Vascular Cellular Adhesion Molecule‐1, Soluble Intercellular Adhesion Molecule‐1, and P‐Selectin

Abstract: The aim of our study was to investigate the influence of single low‐density lipoprotein apheresis (heparin extracorporeal low‐density lipoprotein precipitation [HELP]procedure) on plasma concentrations of soluble adhesion molecules (sAMs) such as soluble vascular cellular adhesion molecule‐1 (sVCAM‐1), soluble intercellular adhesion molecule‐1 (sICAM‐1), and P‐selectin in patients with familial heterozygous hypercholesterolemia and documented coronary artery disease enrolled in a chronic weekly HELP apheresis. Before HELP apheresis, the mean plasma concentration of sVCAM‐1 was 515 ± 119 ng/ml, 204 ± 58 ng/ml for sICAM‐1, and 112 ± 45 ng/ml for P‐selectin. After single HELP apheresis, plasma concentrations of sAM declined significantly by 32 ± 7%, 18 ± 15%, and 33 ± 25% for sVCAM‐ 1,sICAM‐1 and P‐selectin, respectively. After a 1 week interval, sAM concentrations rose to approximately the initial values. The concentrations of all sAMs studied were significantly lower in the plasma leaving than entering the filter. Due to filtration, the decline in plasma level of sVCAM‐1, sICAM‐1, and P‐selectin was 62 ± 19%, 51 ± 39%, and 67 ± 22%, respectively. In addition to lipid reduction, single HELP apheresis significantly lowers plasma concentrations of sVCAM‐1, sICAM‐1, and P‐selectin.     

High‐Efficiency DALI Apheresis Using 1,250 ml Adsorbers in a Hypercholesterolemic Obese Patient: A Case Report

Abstract: 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.