Using the World Apheresis Association Registry Helps to Improve the Treatment Quality of Therapeutic Apheresis.

Therapeutic apheresis (TA) is prescribed to patients that suffer from a severe progressive disease that is not sufficiently treated by conventional medications. A way to gain more knowledge about this treatment is usually by the local analysis of data. However, the use of large quality assessment registries enables analyses of even rare findings. Here, we report some of the recent data from the World Apheresis Association (WAA) registry. Data from >104,000 procedures were documented, and TA was performed on >15,000 patients. The main indication for TA was the collection of autologous stem cells (45% of patients) as part of therapy for therapy. Collection of stem cells from donors for allogeneic transplantation was performed in 11% of patients. Patients with indications such as neurological diseases underwent plasma exchange (28%). Extracorporeal photochemotherapy, lipid apheresis, and antibody removal were other indications. Side effects recorded in the registry have decreased significantly over the years, with approximately only 10/10,000 procedures being interrupted for medical reasons. CONCLUSION: Collection of data from TA procedures within a multinational and multicenter concept facilitates the improvement of treatment by enabling the analysis of and feedback on indications, procedures, effects, and side effects.

Granulocyte/monocyte adsorptive apheresis for the treatment of therapy-refractory chronic active ulcerative colitis.

OBJECTIVES: Current options for patients with steroid-dependent, chronic-active ulcerative colitis (UC) with insufficient response/intolerance to immunosuppressants (ISs) and/or biologics are limited. The aim of this study was to assess the long-term outcome of granulocyte/monocyte adsorptive (GMA) apheresis (Adacolumn®) in this population. MATERIALS AND METHODS: Ninety five adults with steroid-dependent active UC and insufficient response/intolerance to IS and/or TNF inhibitors received 5-8 aphereses in a single induction series of ≤10 weeks. Endpoints included rates of remission (clinical activity index [CAI] ≤ 4) at weeks 24 and 48. RESULTS: Of 94 patients (ITT population), remission and response rates were 34.0% and 44.7% at week 24, and 33.0% and 39.4% at week 48. Among 30 patients with prior failure of IS and biologics, 33.3% and 20.0% were in remission at weeks 24 and 48. At both weeks, 19.2% of patients achieved steroid-free remission. Sustained remission or response occurred in 27.7% of patients at 48 weeks. The cumulative colectomy rate at week 96 was 23.4%. Safety was consistent with previous findings. CONCLUSIONS: This study confirms findings of the 12-week interim analysis and demonstrates that GMA apheresis provides a safe and beneficial long-term outcome for patients with chronic active UC resistant/intolerant to IS and/or TNF inhibitors.

Alirocumab in patients with heterozygous familial hypercholesterolaemia undergoing lipoprotein apheresis: the ODYSSEY ESCAPE trial.

AIM: To evaluate the effect of alirocumab on frequency of standard apheresis treatments [weekly or every 2 weeks (Q2W)] in heterozygous familial hypercholesterolaemia (HeFH). METHODS AND RESULTS: ODYSSEY ESCAPE (NCT02326220) was a double-blind study in 62 HeFH patients undergoing regular weekly or Q2W lipoprotein apheresis. Patients were randomly assigned (2:1, respectively) to receive alirocumab 150 mg (n = 41) or placebo (n = 21) Q2W subcutaneously for 18 weeks. From day 1 to week 6, apheresis rate was fixed according to the patient's established schedule; from weeks 7 to 18, apheresis rate was adjusted based on the patient's low-density lipoprotein cholesterol (LDL-C) response in a blinded fashion. Apheresis was not performed when the LDL-C value was ≥30% lower than the baseline (pre-apheresis) value. The primary efficacy endpoint was the rate of apheresis treatments over 12 weeks (weeks 7-18), standardized to number of planned treatments. In the alirocumab group the least square (LS) mean ± SE (95% confidence interval [CI]) per cent change in pre-apheresis LDL-C from baseline at week 6 was -53.7 ± 2.3 (-58.2 to - 49.2) compared with 1.6 ± 3.1 (-4.7 to 7.9) in the placebo group. The primary efficacy endpoint showed statistically significant benefit in favour of alirocumab (Hodges-Lehmann median estimate of treatment difference: 0.75; 95% CI 0.67-0.83; P < 0.0001). Therefore, alirocumab-treated patients had a 0.75 (75%) additional reduction in the standardized rate of apheresis treatments vs. placebo-treated patients. During this period, 63.4% of patients on alirocumab avoided all and 92.7% avoided at least half of the apheresis treatments. Adverse event rates were similar (75.6% of patients on alirocumab vs. 76.2% on placebo). CONCLUSIONS: Lipoprotein apheresis was discontinued in 63.4% of patients on alirocumab who were previously undergoing regular apheresis, and the rate was at least halved in 92.7% of patients. Alirocumab was generally safe and well tolerated.

Adsorptive cytapheresis for ulcerative colitis with focus on removing platelets and platelet-aggregates.

INTRODUCTION: Platelet abnormalities and secondary thrombocytosis are clinical features of ulcerative colitis (UC) and seem to play a relevant role in pathogenesis. This work analyzed the adsorption characteristics of the adsorber Immunopure. METHODS: A prospective study was performed to investigate the module in vitro with blood from healthy donors in a down-scaled recirculation model and in vivo in six patients suffering from UC. Furthermore, adsorber beads were investigated by immunofluorescence analyses. Apheresis was performed over 5 weeks at weekly intervals. RESULTS: In vitro as well as in vivo, the module showed a strong adsorption of platelets, monocytes, CD14+ CD16+ monocytes, neutrophils, and platelet leukocyte aggregates (PLAs). Five of the six patients benefited from the treatment (83%), and four (67%) went into remission. On average, the CAI was reduced by 6.4 points. CONCLUSION: Immunopure treatments improved the course of the disease and were well tolerated. The module strongly adsorbs platelets and platelet-aggregates.

Beyond dialysis: current and emerging blood purification techniques.

Extracorporeal blood purification using various techniques and hardware is a major part of the modern day practice of clinical nephrology. Although the various modalities of hemodialysis and hemofiltration are the most commonly used extracorporeal therapies in clinical nephrology, blood purification using other techniques have become necessary to remove pathogenic, toxic, or waste substances not easily cleared by hemodialysis or hemofiltration due to factors such as molecular size, protein binding, and lipid solubility. The following review is an up to date summary of extracorporeal therapies, beyond hemodialysis and hemofiltration, in current clinical use as practiced by nephrologists and others in the United States and beyond. This comprises therapeutic apheresis (plasma exchange and cytapheresis), plasma adsorption, hemoperfusion, and the bio-artificial devices.

The German Lipoprotein Apheresis Registry-Summary of the ninth annual report.

During 2012-2020, 89 German apheresis centers collected retrospective and prospective observational data of 2028 patients undergoing regular lipoprotein apheresis (LA) for the German Lipoprotein Apheresis Registry (GLAR). More than 47 500 LA sessions are documented in GLAR. In 2020, all patients treated with LA showed a high immediate median reduction rate of LDL-C (68.2%, n = 1055) and Lp(a) (72.4%, n = 994). Patient data were analyzed for the incidence rate of major coronary events (MACE) 1 and 2 years before the beginning of LA treatment (y-2 and y-1) and prospectively up to 7 years on LA (y + 1 to y + 7). During the first 2 years of LA (y + 1 and y + 2), a MACE reduction of 78% was observed. Current analysis of GLAR data shows very low incidence rates of cardiovascular events in patients with high LDL-C and/or high Lp(a) levels, progressive ASCVD, and maximally tolerated lipid lowering medication regular by LA results.

Novel Leucocyte/Thrombocyte Apheresis for Induction of Steroid-Free Remission in Ulcerative Colitis: A Controlled Randomized Pilot Study.

BACKGROUND AND AIMS: In active ulcerative colitis [UC] refractory to mesalazine, escalation to either steroids or immunosuppression is common practice. The efficacy and safety of alternative escalation therapy with a novel leukocyte apheresis device were studied. METHODS: This was a prospective, randomized, controlled multicentre pilot study comparing leukocyte apheresis with prednisolone in refractory UC (disease activity index [DAI] ≥ 4 and ≤8). Group A received weekly apheresis over five consecutive weeks. Group P received oral prednisolone 40 mg/day tapered to 0 mg at week 6. The primary end point was steroid-free clinical remission [DAI ≤ 2] at week 12. Clinical response was also analysed. RESULTS: Twenty-four patients were enrolled, 13 of whom were randomized into group A and 11 into group P. Clinical remission off steroids at week 12 was achieved in 3/12 patients [25.0%] with apheresis and 2/10 [20.0%] with prednisolone [p = 1.0]. The response rate after 12 weeks was 75.0% in group A and 50.0% in group P. Mean DAI scores improved in both treatment groups [p = 0.008]. C-reactive protein decreased from 6.0 ± 5.3 to 3.8 ± 3.7 mg/L at 12 weeks in group A and increased from 5.2 ± 6.0 to 6.3 ± 7.9 mg/mL in group P. Both treatments were well tolerated. No unexpected serious adverse events were seen in group A. In group P one symptomatic infection with Clostridium difficile occurred. CONCLUSIONS: In patients with active UC refractory to mesalazine a novel leukocyte apheresis showed promising results. A comparison with prednisolone revealed similar therapeutic effectivity and excellent safety, providing the chance to escalate without systemic steroids.

Prospective crossover study for a standardized comparison of the dextrane sulfate whole blood and plasma apheresis system in patients with cardiovascular disease and severe dyslipidemia.

BACKGROUND AND AIMS: The objective of this study was a standardized comparison of the safety and effectiveness of the Kaneka (Kaneka Corporation, Osaka, Japan) whole blood (Liposorber DL-100) and plasma (Liposorber LA-15) lipoprotein apheresis (LA) system to optimize the individual therapy of patients with cardiovascular disease and severe dyslipidemia. METHODS: Six chronic LA patients with a pre-treatment LDL-C < 6 mmol/l in steady state received a total of three treatments with the LA-15 device, followed by three treatments with the DL-100 device or vice versa. To achieve a standardized comparison the treated blood volume for any patient was kept identical for both procedures. Sampling points for total cholesterol, LDL-C, HDL-C, Lp(a), triglyceride, blood count, and bradykinin measurements were adjusted for both techniques. RESULTS: Total cholesterol, LDL-C, HDL-C, Lp(a), and triglycerides were reduced by 59.2 ± 6.5%, 79.3 ± 6.9%, 7.1 ± 3.9%, 87.3 ± 3.1%, 22.5 ± 24.2% using the DL-100 system and by 51.4 ± 5.2%, 65.2 ± 3.7%, 2.2 ± 4.9%, 72.7 ± 2.2%, 46.5 ± 9.4% using the LA-15 system, showing that the DL-100 adsorber was significantly more effective for lowering total cholesterol (p = 0.044), LDL-C (p = 0.001), Lp(a) (p = 0.029), while triglycerides were reduced to a higher extent by the plasma system (p = 0.046) in this patient group. The regenerable LA-15 adsorber columns showed a higher removal capacity considering the difference between inflow and outflow concentrations. Bradykinin levels significantly increased up to 145 fold in the outflow lines using the plasma system (p = 0.028), but not systemically. There was no significant bradykinin generation using the whole blood adsorber. CONCLUSION: In conclusion, the whole blood system was faster and more effective in this LA patient group with pre apheresis LDL-C<6 mmol/l. Whether the regenerable plasma system is more effective in patients with higher LDL-C content should be evaluated in future standardized comparisons.

Rationale and design of MultiSELECt: A European Multicenter Study on the Effect of Lipoprotein(a) Elimination by lipoprotein apheresis on Cardiovascular outcomes.

BACKGROUND: Dyslipidemia is a well-known risk factor for atherosclerosis and subsequent cardiovascular disease (CVD). While low density lipoprotein cholesterol (LDL-C) is well-established and taken into consideration for risk management and therapy, lipoprotein(a) is another established CVD risk factor frequently not undergoing screening due to a lack of medical treatment options. For patients suffering from CVD due to massive elevation of Lp(a) in presence of normal LDL-C levels, lipoprotein apheresis is the only available treatment option. While this constellation is an accepted indication for lipoprotein apheresis (LA) in Germany, prospective studies including a control group are still lacking. OBJECTIVE: Primary objective of this trial is to evaluate the clinical benefit of lipoprotein apheresis on myocardial infarction, PCI, CABG and death from cardiovascular disease in subjects with elevated Lp(a). This study evaluates the clinical benefit of weekly LA in subjects with progressive cardiovascular disease, as accepted by the German Federal Joint Committee (treatment group). Comparator will be well-matched subjects under maximum tolerated lipid lowering therapy without access to LA treatment (control group). METHODS: MultiSELECt, is a prospective, multicenter, multinational, two-arm matched-pair cohort study designed to directly compare subjects with significantly elevated Lp(a) approved for LA subsequently undergoing weekly apheresis treatment versus a continuation of maximal medical therapy. The follow-up period will be 2 years after the baseline visit and until at least 60 events of the primary end-point occurred in the control group. A central trial expert committee will review all subjects with respect to their potential indication for LA according to established German guidelines in a blinded fashion. All control subjects will be contacted monthly via telephone visits to compensate for the more frequent visits during apheresis. Approximately 150 matched pairs will be necessary to detect an event reduction of at least 10% in subjects under LA treatment. CONCLUSION: The MultiSELECt trial provides the unique opportunity to demonstrate the efficiency of LA on CVD in patients with elevated Lp(a) under strongly controlled conditions.

Efficacy of lipid reduction with DALI and MONET.

BACKGROUND: Lipidapheresis techniques are increasingly used to treat drug-resistant hyperlipidemia but few efficacy studies under routine application are available. In this multicenter observational study we investigated direct adsorption of lipoproteins (DALI) and lipoprotein filtration (MONET) for the short and the long-term effects on lipid-lowering effects. METHODS: Data of 122 apheresis patients from 11 centers (DALI: n = 78, MONET: n = 44) were prospectively collected for a period of 2 years. Routine lipid measurements were evaluated (2154 DALI and 1297 MONET sessions). It was investigated whether the relative reduction of LDL-C during apheresis session achieves at least 60%. Also relative reduction of total cholesterol, HDL, triglyceride, and Lp(a) were analyzed. RESULTS: The relative reduction of LDL-C was at least 60%: DALI: 70.62%, 95% CI = [69.34; 71.90] and MONET: 64.12%, 95% CI = [60.79; 67.46]. Also triglycerides were reduced with both systems: DALI 38.63%, 95% CI = [33.95; 43.30] vs. MONET 57.68%, 95% CI = [51.91; 63.45]. Relative reductions of total cholesterol were in the range of 50% (DALI 95% CI = [46.49; 49.65] MONET 95% CI = [48.93; 55.26]) and of Lp(a) in the range of 65% (DALI 95% CI = [61.92; 65.83] MONET 95% CI = [63.71; 70.30]. HDL reduction was: DALI 15.01%, 95% CI = [13.22; 16.79] and MONET 22.59%, 95% CI = [19.33; 25.84]. For both devices treated patient plasma/blood volume and in case of DALI the use of the larger adsorber configurations (DALI 1000 and DALI 1250) were independent positive predictors of the relative reduction of LDL-C and of Lp(a). CONCLUSIONS: Both systems effectively improved lipid profile and reduced atherogenic lipids. The results point to the importance of the individualized application of these valuable therapies to achieve clinical targets.

Safety aspects of lipidapheresis using DALI and MONET - Multicenter observational study.

BACKGROUND: Lipidapheresis was introduced for intractable hyperlipidemia as a more selective therapy than plasma exchange aiming to enhance efficacy and limit side-effects. Although this therapy is regarded safe, multicenter data from routine application are limited. We investigated direct adsorption of lipoproteins (DALI) and lipofiltration (MONET) regarding the short and the long-term safety aspects. METHODS: This multicenter observational study prospectively evaluated 2154 DALI and 1297 MONET sessions of 122 patients during a period of 2 years. Safety parameters included clinical side-effects (adverse device effects, ADEs), technical complications, blood pressure and pulse rate. Also routinely performed laboratory parameters were documented. Analysis of laboratory parameters was not corrected for blood dilution. RESULTS: Overall 0.4% DALI and 0.5% MONET treatments were affected by ADE. Technical complications occurred in 2.1% and in 0.8% DALI and MONET sessions, respectively. The most frequent ADE was hypotension, and the majority of technical problems were related to vascular access. Both types of treatments led to a drop of thrombocytes in the range of 7-8%. Hematocrit and erythrocytes decreased only during the DALI treatments by about 6%. Leucocytes decreased during the DALI therapy (∼15%), whereas they increased during the MONET application (∼11%). MONET treatment was associated with a higher reduction of proteins (fibrinogen: 58% vs. 23%, albumin: 12% vs. 7%, CRP: 33% vs. 19% for MONET and DALI, respectively). Apart from severe thrombocytopenia in two DALI patients, changes of other parameters were typically transient. CONCLUSIONS: Under routine use the frequency of side-effects was low. Still, monitoring of blood count and proteins in chronic apheresis patients is recommended.

Alirocumab in patients with heterozygous familial hypercholesterolemia undergoing lipoprotein apheresis: Rationale and design of the ODYSSEY ESCAPE trial.

BACKGROUND: Many patients with heterozygous familial hypercholesterolemia (HeFH) fail to reach optimal low-density lipoprotein cholesterol (LDL-C) levels with available lipid-lowering medications, including statins, and require treatment using alternative methods such as lipoprotein apheresis. OBJECTIVE: To evaluate the efficacy of alirocumab 150 mg every 2 weeks (Q2W) compared with placebo in reducing the frequency of lipoprotein apheresis treatments in patients with HeFH. METHODS: ODYSSEY ESCAPE is a randomized, double-blind, placebo-controlled, parallel-group, 18-week, phase 3 study being conducted in the United States and Germany. ODYSSEY ESCAPE will evaluate the efficacy and safety of alirocumab in approximately 63 adults with HeFH undergoing regular weekly (QW; for ≥4 weeks) or Q2W (for ≥8 weeks) lipoprotein apheresis. Patients will be randomly assigned (2:1, respectively) to receive alirocumab 150 mg subcutaneously Q2W or placebo subcutaneously Q2W (both in 1-mL injections) for 18 weeks. From day 1 to week 6, the apheresis frequency will be fixed to the individual patient's established schedule (QW or Q2W); thereafter, apheresis will be performed according to the LDL-C value at that visit: apheresis will not be performed when the LDL-C value is ≥30% lower than the baseline pre-apheresis LDL-C value. The primary end point is the frequency of apheresis treatments over a 12-week period starting at week 7. DISCUSSION: The ODYSSEY ESCAPE trial will determine whether alirocumab reduces the frequency of lipoprotein apheresis in patients with HeFH.

First data from the German Lipoprotein Apheresis Registry (GLAR).

OBJECTIVE: In recent years the Federal Joint Committee (G-BA), a paramount decision-making body of the German health care system challenged the approval of diagnostic and therapeutic procedures for regular reimbursement, including lipoprotein apheresis therapy. Years before an interdisciplinary German apheresis working group, established by members of both German Societies of Nephrology (Verband Deutsche Nierenzentren (VDN), Deutsche Gesellschaft für Nephrologie (DGfN)), initiated a revision of the indication of lipoprotein apheresis therapy according to current guidelines and recommendations for the treatment of lipid disorders. This working group was convinced, that data derived from a registry would support lipoprotein apheresis as a therapy for severe hyperlipidemic patients suffering from progressive cardiovascular diseases. METHODS AND RESULTS: In 2009 the working group established the indication for lipoprotein apheresis with respect to current cardiovascular guidelines and scientific knowledge for the registry, which are in line with the reimbursement guidelines. In 2011 financing by sponsors was secured and an internet-based registry was created. A pilot project with 5 apheresis centers finished in 2012 - since then the registry is available to all German apheresis centers. CONCLUSIONS: There has been consensus between the medical societies and health care carriers regarding the need for a German Lipoprotein Apheresis Registry (GLAR). The launch of this registry complies with requirements of the Federal Joint Committee (G-BA). Complementing the Pro(a)LiFe-Study, first data from GLAR support the safety of the different apheresis treatment procedures. In addition these first data suggest, with respect to the results of Pro(a)LiFe-Study, effectiveness in preventing cardiovascular progression as well. Here, further data are needed to statistically substantiate these early findings.

Extracorporeal fibrinogen adsorption--efficacy, selectivity and safety in healthy subjects and patients with foot ulcers.

The elimination of fibrinogen from plasma improves plasma viscosity and whole blood viscosity. For extracorporeal adsorption of fibrinogen the pentapeptide gly-pro-arg-pro-lys was coupled to sepharose CL-4B. Columns containing 100 ml of coupled sepharose CL-4B were used to eliminate fibrinogen from the plasma of 8 healthy male subjects (mean age 27.4 +/- 4.3 years, height 180.9 +/- 8.3 cm, weight 85.1 +/- 13.6 kg). Four treatments were performed in each proband (days 1, 2, 4 and 7). Plasma fibrinogen concentration was lowered from 221.1 +/- 39.0 to 123.5 +/- 21.7 mg/dl (2275 +/- 477 ml plasma treated) by the first treatment, from 172.8 +/- 42.3 to 105.6 +/- 16.5 mg/dl (1609 +/- 761 ml) by the second, from 140.5 +/- 13.8 to 98.8 +/- 8.6 mg/dl (1224 +/- 118 ml) by the third and from 160.2 +/- 23.6 to 106.4 +/- 9.7 mg/dl (1513 +/- 521) by the fourth. Plasma viscosity was improved from 1.40 +/- 0.18 mPa s before the first treatment to 1.23 +/- 0.06 mPa s after fourth treatment, whole blood viscosity from 4.49 +/- 0.36 mPa s to 3.83 +/- 0.27 mPa s (P < 0.01). No clinical side effects and no clinically relevant change of laboratory parameters including in vitro tests on thrombocyte function were observed. Seven men and three women (48-75 years old, 9 patients suffered from diabetes mellitus, one patient from peripheral arterial occlusive disease, 5 patients were on regular hemodialysis) were treated by fibrinogen adsorption. Each column contained 135 ml of coupled sepharose CL-4B. Treatments were scheduled on day 1, 2, 4, 6, 8, 10, 13, 16, 19, 22, 25 and 28. 144 treatments with fibrinogen adsorption were performed. No clinical side effects due to the fibrinogen-adsorption procedure were observed. In these 10 patients the fibrinogen concentration before the first treatment was 473.7 +/- 183.7 mg/dl. In the first treatment session it was lowered to 241.4 +/- 125.8 mg/dl by treating 4270 +/- 1180 ml of plasma. In the following 134 treatments the pre-treatment concentration of fibrinogen was 262.6 +/- 83.4 mg/dl, the post-treatment concentration was 120.6 +/- 37.2 mg/dl. The mean volume of plasma treated was 3737 +/- 1643 ml, the mean duration of a treatment session (except the first treatment) was 143.7 +/- 63.1 min. In 7 patients a mean post-treatment fibrinogen concentration of < or = 123 mg/dl was obtained, in the other patients 133, 177 and 184 mg/dl. Yet, the decrease of fibrinogen concentration was also pronounced in these 3 patients: -82%, -67%, and -73%, respectively. Accelerated wound healing was observed in 9 of the 10 patients. In conclusion, affinity chromatography using the pentapeptide gly-pro-arg-pro-lys is an effective, selective and safe procedure to lower fibrinogen concentration in plasma thereby improving blood viscosity. It could be a therapeutic option in severe blood vessel disease where drug therapy is not sufficient and invasive procedures like bypass or angioplasty cannot be applied.

First human application of a novel adsorptive-type cytapheresis module in patients with active ulcerative colitis: a pilot study.

The aim of this study was to evaluate the safety, tolerability, technical performance and clinical efficacy of a novel adsorptive-type cytapheresis module in patients with active ulcerative colitis. Ten patients with ulcerative colitis (clinical activity index 6-10) were recruited. The new adsorber (Nikkiso, Tokyo, Japan) was specifically designed to remove platelets, granulocytes and monocytes from peripheral blood using an extracorporeal circulation. Cytapheresis treatments were performed weekly for five consecutive weeks (each with a 60-min duration). Safety and tolerability were evaluated by investigating vital parameters, routine laboratory tests, adverse event reporting and a questionnaire. Disease activity was evaluated by assessing the clinical activity index as well as the endoscopic index, according to Rachmilewitz. Technical performance and biocompatibility were investigated by repeated measurements of cellular blood count, complement factor C3a and cell surface markers before, during and after the apheresis treatments. The cytapheresis treatments were "well" to "very well" tolerated by the patients. All measured safety parameters remained essentially unchanged. Performance data showed that platelets, monocytes and neutrophil granulocytes were effectively reduced during the cytapheresis treatments. Apheresis treatment was associated with high remission rates (80% at week 10). Clinical remission was accompanied by the reduction of the endoscopic index in four out of the nine eligible patients. Levels of C3a did not significantly increase during cytapheresis treatments. The novel device has been shown to be safe, well tolerated and clinically efficient. It offered a very good biocompatibility and platelet elimination capacity.

Albumin dialysis molecular adsorbents recirculating system: impact of dialysate albumin concentration on detoxification efficacy.

Albumin dialysis with the molecular adsorbent recirculating system (MARS) or single pass albumin dialysis (SPAD) uses human serum albumin (HSA) as an addendum of the dialysate fluid. The purpose of this in vitro study was to evaluate the impact of the dialysate albumin concentration on removal efficacy. Heparinized human plasma (3 L/test) was spiked with creatinine (1000 mg/L), unconjugated bilirubin (100 mg/L), chenodeoxycholic acid (CDCA) (100 mg/L), and diazepam (3 mg/L). The MARS albumin circuit was primed with different amounts of HSA (150, 100, 60, and 40 g). The plasma, albumin, and dialysate flow rates were 200, 200, and 40 mL/min, respectively. Clearances were calculated based on repeated sampling during the experiments, which lasted 480 min. The effective HSA concentrations in the dialysate were 175, 115, 77, and 46 g/L, respectively. They decreased over treatment time to 147, 99, 63, and 41 g/L, respectively, due to surface adsorption. The plasma-HSA concentration remained unchanged over time in all experiments (average 39 g/L). The creatinine clearance was not impacted by dialysate HSA concentration. For the albumin-bound markers a clear correlation between HSA-concentration and clearance was demonstrated with the highest clearances for the 100 and 150 g HSA experiments. The 100 g HSA setup appeared to be the one with best cost-benefit ratio, resulting in clearances (after 1 h of treatment) of 31 mL/min creatinine, 0.3 mL/min unconjugated bilirubin, 11 mL/min CDCA, and 35 mL/min diazepam. Low albumin concentrations, such as in SPAD, result in low clearance rates for albumin-bound substances. The optimal clearances in these experiments were reached with a priming dose of 100 g HSA.

Longitudinal cohort study on the effectiveness of lipid apheresis treatment to reduce high lipoprotein(a) levels and prevent major adverse coronary events.

BACKGROUND: We investigated in a longitudinal, multicenter, cohort study whether combined lipid apheresis and lipid-lowering medication can reduce extremely high levels of lipoprotein(a) (Lp[a]) and thus prevent major adverse coronary events (MACE) more efficaciously than lipid-lowering medication alone. METHODS: Eligible patients had coronary artery disease and Lp(a) levels > or =2.14 micromol/l (95th percentile). All patients received lipid-lowering medications alone until maximally tolerated doses were no longer effective, followed by combined lipid apheresis and lipid-lowering medication. The rates of the primary outcome, MACE, were recorded for both periods. RESULTS: A total of 120 patients were included. The mean duration of lipid-lowering therapy alone was 5.6+/-5.8 years, and that of apheresis was 5.0+/-3.6 years. Median Lp(a) concentration was reduced from 4.00 micromol/l to 1.07 micromol/l with apheresis treatment (P<0.0001); the corresponding mean annual MACE rate per patient was 1.056 versus 0.144 (P<0.0001). CONCLUSIONS: Lowering of Lp(a) levels by apheresis was efficacious and safe, and we recommend this therapy for patients in whom maximally tolerated doses of medication alone have failed to control coronary artery disease-associated events.

Reduction of dendritic cells by granulocyte and monocyte adsorption apheresis in patients with ulcerative colitis.

The influence of the granulocyte/monocyte apheresis (GMCAP) on cell populations participating in mechanisms of tolerance, e.g. dendritic cells (DCs), is still not very clear. In a first step, we aimed to investigate changes in the DC population of patients suffering from ulcerative colitis (UC) (n = 13) compared to healthy subjects (n = 9). In a second step, we studied the changes in peripheral DCs in a small group of patients with active UC before and after Adacolumn apheresis (n = 7). For this purpose, plasmacytoid and myeloid DCs and their maturation markers CD40, CD80, and CD86 were measured using four-color flow cytometry in the peripheral blood. After apheresis, and in acute flare-ups, we identified a significantly lower number of lymphocytes, plasmacytoid, and myeloid DCs. In conclusion, the additional removal of peripheral DCs by GMCAP, which otherwise would contribute to the inflammatory process in the gut, may lead to a higher tolerogeneic status towards luminal antigens.

Leukocytapheresis (LCAP) in the management of chronic active ulcerative colitis--results of a randomized pilot trial.

Recent studies suggest that leukocytapheresis with Cellsorba is a valuable therapy for ulcerative colitis after failure of conventional treatment. In this study the potential of leukocytapheresis to induce remission in refractory chronic colitis under the conditions of European treatment guidelines was investigated. The therapeutic benefit of leukocytapheresis in the maintenance of remission was additionally elucidated. Twenty patients were treated weekly for 5 weeks. A significant decrease in the activity index was observed. Fourteen patients achieved clinical remission, and mucosal healing was observed endoscopically in six patients. After randomization these 14 patients in remission entered a second period of either monthly leukocytapheresis or no further treatment. In both groups steroids were tapered down. After 6 months, only one patient in the control group remained in remission, in contrast to five of eight patients in the leukocytapheresis group. In conclusion, leukocytapheresis may offer a therapeutic option in the induction and the maintenance of remission in chronic active ulcerative colitis.