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ZUSAMMENFASSUNGInsbesondere die schwere Hypertriglyzeridämie (SHTG) führt zu einem erhöhten Risiko für eine besonders schwer verlaufende Pankreatitis. In der Akutsituation einer SHTG-Pankreatitis müssen die Triglyzeride sehr rasch gesenkt werden, um einen weiteren Organschaden zu verhindern. Mithilfe der therapeutischen Apherese in Form des Plasmaaustausches oder der Doppelfiltrations-Plasmapherese (DFPP) gelingt dies effektiv und sicher. Für Patienten mit rezidivierender SHTG-Pankreatitis kann eine Langzeittherapie mit Apherese zusätzlich zu Diät, Lebensstilmaßnahmen und medikamentöser Therapie ein wichtiges Therapiemodul zur Prävention erneuter Ereignisse sein. In der Schwangerschaft ist jede zweite Pankreatitis durch zu hohe Triglyzeride verursacht. Bei fortbestehender Fettstoffwechselstörung kann die therapeutische Apherese eine Therapieoption sein, um ein solches für den Fötus und die Mutter lebensbedrohliches Ereignis zu verhindern.

ZUSAMMENFASSUNGIn Deutschland ist der Einsatz der therapeutischen Apherese (TA) vorrangig ein nephrologisches Therapieangebot. International ist der Fachbezug heterogener. Abhängig von Zulassungsstatus und Erfahrungswerten werden bei gleicher Indikation unterschiedliche Methoden bevorzugt. Der unselektive Plasmaaustausch ist in weiten Teilen der Welt unverändert das Standardverfahren. Deutschland und Japan sind die Pioniere der selektiven Verfahren wie der Immunadsorption und Doppelfiltrations-Plasmapherese. Unter den interdisziplinären Leitlinien zum Einsatz der TA sind für die Praxis in Deutschland der Apherese-Standard der Deutschen Gesellschaft für Nephrologie (DGfN) und die Leitlinien der American Society for Apheresis (ASFA) hervorzuheben. Die Leitlinien der Deutschen Gesellschaft für Neurologie e. V. (DGN) sind als nationale fachbezogene Leitlinien zu erwähnen, da die TA bei vielen neurologischen Erkrankungen zum Einsatz kommt und sehr differenziert empfohlen wird. Das neurologische Konsensuspapier zur TA fasst dies aktuell zusammen. Im Jahr 2019 wurden die 3 Werke aktualisiert bzw. erstmals vorgelegt.

Background: Severe hypertriglyceridemia (HTG) is associated with major complications such as acute or relapsing pancreatitis (AP) and atherosclerotic cardiovascular disease (ASCVD). Rapid elimination of triglyceride (TG)-rich lipoproteins (LP) with double filtration plasmapheresis (DFPP) without need for substitution has been found to be effective for the acute, short-term treatment of HTG-induced AP. Data on the long-term use of DFPP to prevent HTG-associated complications are scarce. Objectives: To evaluate the use and efficacy of regular DFPP treatment in clinical practice for preventing recurrence of HTG-associated complications in thera­py refractory patients. Methods: Retrospective multicenter study in patients with severe symptomatic drug and diet refractory HTG with regular DFPP treatment. Patients’ incidence of HTG-associated pancreatic or cardiovascular complications was compared before treatment and with regular DFPP treatment. Results: Ten patients (3 female) were identified with baseline maximal TG concentrations of 2,587–28,090 mg/dL (median 5,487 mg/dL; interquartile range [IQR] 4,340–12,636). The mean observation period was 3.9 ± 3.4 years before and 3.8 ± 3.0 years after commencement of DFPP. In 5 patients, severe HTG was related to chylomicronemia, 2 patients had familial partial lipodystrophy Dunnigan, and 1 patient had additional LP(a)-hyperlipoproteinemia. The main HTG-associated complication was recurrent AP in 8 patients, including 1 patient treated during pregnancy. Two patients presented severe progressive ASCVD. With long-term DFPP treatment, the annual rate of HTG-associa­ted pancreatic or cardiovascular complications declined from median 1.4 (IQR 0.7–2.6) to 0 (IQR 0.0–0.4; p < 0.005). The absolute number of events was reduced by 77%. In 6 patients (60%) episodes of AP did not occur, nor was progression of ASCVD detected clinically or by routine imaging techniques. DFPP was effective in the elimination of TG-rich LP from plasma, and was safe and well-tolerated. Conclusion: Long-term, regular DFPP treatment resulted in stabilization of patients with severe HTG and related recurrent AP or progression of ASCVD, who were refractory to conventional dietary and drug therapy.

Lipoprotein(a) (Lp(a)) consists of an LDL particle whose apolipoprotein B (apoB) is covalently bound to apolipoprotein(a) (apo[a]). An increased Lp(a) concentration is a causal, independent risk factor for atherosclerotic cardiovascular disease (ASCVD) and a predictor of incident or recurrent cardiovascular events. Although Lp(a) was first described as early as 1963, only the more recent results of epidemiological, molecular, and genetic studies have led to this unequivocal conclusion. More than 20% of Western populations have elevated Lp(a) values. Lp(a) concentrations should be always part of the lipid profile when ASCVD risk is assessed. However, presence of other risk factors, laboratory findings, medical history and family history must be considered to conclude on its clinical relevance in an individual patient. Early or progressive ASCVD or a familial predisposition are key findings which can be associated with elevated Lp(a). The cholesterol portion contained in Lp(a) is also included in the various methods of LDL-C measurement. To assess proximity to the cardiovascular risk related target value for LDL-C, appropriate correction should be applied when high Lp(a) values are obtained to estimate the LDL-C that can actually be treated by lipid lowering drugs. Initial study data show that antisense oligonucleotides, which selectively decrease apolipoprotein(a), are promising as future treatment options. Currently, lipoprotein apheresis, which has a reimbursement guideline in Germany, is the therapy of choice for patients with Lp(a)-associated progressive ASCVD, with the aim of sustained prevention of further cardiovascular events.

Autoimmune encephalitis is a severe inflammatory disorder of the brain. The discovery that several non-infectious forms of encephalitis are associated with autoantibodies was a breakthrough in the care of this previously untreatable group of patients. The correlation of antibody type and titer with pattern and severity of symptoms was essential for the initiation of immunotherapies. First line therapy consists of steroids, intravenous immunoglobulins, plasma exchange or immunoadsorption. Rapid elimination of autoantibodies using selective immunoadsorption and avoiding the disadvantage of plasma substitution is a pathophysiologically guided therapeutic approach, and has been proven to be an effective therapeutic option as part of multimodal immunotherapy.

Lipoprotein(a) (Lp(a)) is an independent cardiovascular risk factor playing a causal role for atherosclerotic cardiovascular disease (CVD). Lipoprotein apheresis (LA) is a safe well-tolerated outpatient treatment to lower LDL-C and Lp(a) by 60–70%, and is the ultimate escalating therapeutic option in patients with hyperlipoproteinemias (HLP) involving LDL particles. Major therapeutic effect of LA is preventing cardiovascular events. Lp(a)-HLP associated with progressive CVD has been approved as indication for regular LA in Germany since 2008. The Pro(a)LiFe-study investigated with a prospective multicenter design the long-term preventive effect of LA on incidence rates of cardiovascular events prospectively over a period of 5 years in 170 consecutive patients who commenced regular LA. During a median period of 4.7 years of the pre-LA period, Lp(a) associated progressive CVD became apparent. Apolipoprotein(a) (apo(a)) isoforms and polymorphisms at the apo(a) gene (LPA) were analyzed to assess hypothetical clinical correlations. 154 patients (90.6%) completed 5‑years follow-up. Significant decline of the mean annual major adverse cardiac event (MACE) rate was observed from 0.41 ± 0.45 two years prior to regular LA to 0.06 ± 0.11 during 5 years with regular LA (p < 0.0001). 95.3% of patients expressed at least one small apo(a) isoform. Calculation of isoform specific concentrations allowed to confirm the equivalence of 60 mg/dl or 120 nmol/l as Lp(a) thresholds of the German LA guideline. Results of 5 years prospective follow-up confirmed that LA has a lasting effect on prevention of cardiovascular events in patients with Lp(a)-HLP and afore progressive CVD.

High concentrations of lipoprotein(a) (Lp(a)) represent an important independent and causal risk factor associated with adverse outcome in atherosclerotic cardiovascular disease (CVD). Effective Lp(a) lowering drug treatment is not available. Lipoprotein apheresis (LA) has been proven to prevent cardiovascular events in patients with Lp(a)-hyperlipoproteinemia (Lp(a)-HLP) and progressive CVD. Here we present the course of a male patient with established peripheral arterial occlusive disease (PAOD) at the early age of 41 and coronary artery disease (CAD), who during follow-up developed over 2 years a progressive syndrome of cerebellar and spinal cord deficits against the background of multifactorial cardiovascular risk including positive family history of CVD. Spastic tetraplegia and dependency on wheel chair and nursing care represented the nadir of neurological deficits. All conventional risk factors including LDL-cholesterol had already been treated and after exclusion of other causes, genetically determined Lp(a)-HLP was considered as the major underlying etiologic factor of ischemic vascular disease in this patient including spinal cord ischemia with vascular myelopathy. Treatment with an intensive regimen of chronic LA over 4.5 years now was successful to stabilize PAOD and CAD and led to very impressive neurologic and overall physical rehabilitation and improvement of quality of life. Measurement of Lp(a) concentration must be recommended to assess individual cardiovascular risk. Extracorporeal clearance of Lp(a) by LA should be considered as treatment option for select patients with progressive Lp(a)-associated ischemic syndromes.

Lipoprotein(a) (Lp(a)) is an independent cardiovascular risk factor playing a causal role for atherosclerotic cardiovascular disease (ASCVD). Early or progressive ASCVD or a familial predisposition are key findings which can be associated with Lp(a)-hyperlipoproteinemia (Lp(a)-HLP). The German guideline for the indication of lipoprotein apheresis in patients with Lp(a)-HLP has proved to be of value to identify patients at highest risk, using the composite of a Lp(a) threshold >60 mg/dl (>120 nmol/l) and clinical ASCVD progression despite effective LDL-C lowering therapy. In particular for such patients it appears to be plausible that Lp(a)-associated risk would increase cardiovascular mortality as the most important part of total mortality in Western populations. By the majority of existing investigations an association of Lp(a) concentration on total or cardiovascular mortality was demonstrated. However, inconsistency in the findings between studies exists without a clear trend for any study feature to explain this. Genetic homogeneity of the population, long-term follow-up, and clinically guided selection of patients might be important to further clarify the impact of Lp(a) concentration on progression of ASCVD, and finally total or cardiovascular mortality. LDL and Lp(a) particles exhibit a mutual effect modification on related ASCVD risk. Therefore, LDL-C levels and concomitant LDL-C lowering treatment must be considered in this context. Prospective evaluation is needed to document that specific Lp(a)-lowering additional to targeted LDL-C lowering will in fact reduce cardiovascular or total mortality.

In der Schwangerschaft kann die therapeutische Apherese eine rasch wirksame, risikoarme Option zur Behandlung von akuten therapierefraktaren Verlaufen bestimmter Erkrankungen darstellen oder als primare Therapiealternative dienen, wenn die regularen Medikamente aufgrund der Schwangerschaft nicht einsetzbar sind. Selektive Verfahren wie die Immunadsorption und die Lipoproteinapherese ersetzen zunehmend bei vielen Indikationen den unspezifischen Plasmaaustausch. Dargestellt wird eine Ubersicht zum Einsatz der therapeutischen Apherese in der Schwangerschaft bei immunologischen Krankheitsbildern des Nervensystems und weiterer Organsysteme sowie bei metabolischen Erkrankungen.

Elevated lipoprotein(a) (Lp(a)) has emerged as an important independent cardiovascular risk factor, and causal association has been accepted with adverse outcome in atherosclerotic disease. Lipoprotein apheresis (LA) can lower low-density lipoprotein (LDL)-cholesterol and Lp(a) by 60-70 % and is the final escalating therapeutic option in patients with hyperlipoproteinemias (HLP) involving LDL or Lp(a) particles. Major therapeutic effect of LA is preventing cardiovascular events. Stabilizing plaque morphology might be an important underlying mechanism of action. In Germany, since 2008, a reimbursement guideline has been implemented to establish the indication for LA not only for familial or severe forms of hypercholesterolemia but also for Lp(a)-HLP associated with a progressive course of cardiovascular disease, that persists despite effective treatment of other concomitant cardiovascular risk factors, i.e. isolated Lp(a)-HLP. The Pro(a)LiFe-study confirmed with a prospective multicenter design that LA can effectively reduce Lp(a) plasma levels and prevent cardiovascular events.

Background: Up to every fourth woman with multiple sclerosis (MS) or neuromyelitis optica spectrum disorder (NMOSD) suffers a clinically relevant relapse during pregnancy. High doses of steroids bear some serious risks, especially within the first trimester of pregnancy. Immunoadsorption (IA) is an effective and more selective treatment option in disabling MS relapse than plasma exchange. Data on the use of IA during pregnancy and breastfeeding are scarce. Methods: In this retrospective multicenter study, we analyzed the safety and efficacy of IA treatment in acute relapses during pregnancy or breastfeeding. The primary outcome parameter - change of acute relapse-related disability after IA - was assessed using Expanded Disability Status Scale (EDSS) and visual acuity (VA) measurements for patients with optic neuritis (ON). Results: A total of 24 patients were analyzed, 23 with relapsing–remitting MS, and 1 with NMOSD. Twenty patients were treated with IA during pregnancy. Four patients received IA postnatally during the breastfeeding period. Treatment was started at a mean 22.5 [standard deviation (SD) 13.9] days after onset of relapse. Patients were treated with a series of 5.8 (mean, SD 0.7) IA treatments within 7–10 days. Sixteen patients received IA because of steroid-refractory relapse, eight were treated without preceding steroid pulse therapy. EDSS improved clinically relevant from 3.5 [median, interquartile range (IQR) 2] before IA to 2.5 (median, IQR 1.1) after IA, p < 0.001. In patients with ON, VA improved in four out of five patients. Altogether, in 83% of patients, a rapid and marked improvement of relapse-related symptoms was observed after IA with either a decrease of ⩾1 EDSS grade or improvement in VA ⩾20%. No clinically relevant side effect was reported in 138 IA treatments. Conclusions: Tryptophan-IA was found to be effective and well tolerated in MS/NMOSD relapses, both as an escalation option after insufficient response to steroid pulse therapy and as first-line relapse treatment during pregnancy and breastfeeding.

Bei der Kostenerstattung der therapeutischen Apherese mussen stationarer und ambulanter Bereich unterschieden werden. Innerhalb des G-DRG-Systems (G-DRG: German Diagnosis-Related Groups) bilden die OPS-Codes (OPS: Operationen- und Prozedurenschlussel) der Zusatzentgelte die formale Grundlage fur den stationaren Einsatz des Plasmaaustauschs und der selektiven therapeutischen Apherese. Im ambulanten Bereich gehoren die Lipidapherese (LA) fur schwere Fettstoffwechselstorungen und die Immunadsorption (IA) bei therapierefraktarer rheumatoider Arthritis zum festen Leistungskatalog der GKV, wobei letztere in der Praxis keine Rolle mehr spielt. Der daruber hinaus gehende ambulante Einsatz der Apheresetherapie bei seltenen Krankheitsbildern oder sehr speziellen Verlaufssituationen schwerer Erkrankungen erfordert eine muhsame individuelle Antragstellung bei den Kostentragern.

Objective— Lipoprotein(a)-hyperlipoproteinemia (Lp(a)-HLP) along with progressive cardiovascular disease has been approved as indication for regular lipoprotein apheresis (LA) in Germany since 2008. We aimed to study the long-term preventive effect of LA and to assess hypothetical clinical correlations of apolipoprotein(a) (apo(a)) by analyzing genotypes and phenotypes. Approach and Results— This prospective observational multicenter study included 170 patients with Lp(a)-HLP and progressive cardiovascular disease (48.9 years median age at diagnosis) despite other cardiovascular risk factors, including low-density lipoprotein cholesterol had maximally been treated (mean baseline low-density lipoprotein cholesterol: measured, 2.56 mmol/L [98.9 mg/dL] and corrected, 1.72 mmol/L [66.3 mg/dL]). Patients were prospectively investigated during a 5-year period about annual incidence rates of cardiovascular events. In addition, apo(a) isoforms and polymorphisms at the apo(a) gene ( LPA ) were characterized. One hundred fifty-four patients (90.6%) completed 5 years of follow-up. Mean Lp(a) concentration before commencing regular LA was 108.1 mg/dL. This was reduced by a single LA treatment by 68.1% on average. Significant decline of the mean annual cardiovascular event rate was observed from 0.58±0.53 2 years before regular LA to 0.11±0.15 thereafter ( P Conclusions— Results of 5 years of prospective follow-up confirm that LA has a lasting effect on prevention of cardiovascular events in patients with Lp(a)-HLP. Patients clinically selected by progressive cardiovascular disease were characterized by a highly frequent expression of small apo(a) isoforms. Only Lp(a) concentration seemed to comprehensively reflect Lp(a)-associated cardiovascular risk, however.

Background: A marked proportion of multiple sclerosis (MS) relapses is followed by incomplete recovery. Our aim was to considerably increase the evidence of the clinical use of immunoadsorption (IA) as escalation therapy for patients with MS relapse. Methods: A retrospective multicenter study was performed in MS patients with steroid refractory relapse who were treated with tryptophan IA. The main outcome parameter was change of acute relapse-related disability assessed by Expanded Disability Status Scale (EDSS) and visual acuity (VA) measurements for patients with optic neuritis (ON). IA treatments were performed using single-use tryptophan adsorbers. Results: Data of 147 MS patients and 786 single IA treatments were analyzed. Treatment with IA was commenced in mean 32 ± 35 days after the onset of relapse. One hundred and five out of 147 patients (71.4%) improved functionally after mean 5.4 IA treatments within 7-10 days. EDSS improved from median 5 (interquartile range, IQR 3.5) to 4 (IQR 2.5) (p < 0.001). In patients with ON (n = 32), VA improved after the IA series in 84% of cases from median 0.2 (IQR 0.6) to 0.6 (IQR 0.66) (p < 0.001). In 98.9% of IA treatments, no clinically relevant side effect was reported. Conclusion: Tryptophan IA was found to be effective and well tolerated as escalation therapy for MS relapse.

Background/Aims: First-line treatment options for chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) are corticosteroids, intravenous immunoglobulin, and plasma exchange. In a significant number of patients, first-line therapy fails, and long-term maintenance treatment still remains a therapeutic challenge. Immunoadsorption (IA) may be an alternative to classical plasma exchange in the therapy of immune-mediated neurologic diseases. The aim of this investigation was to evaluate efficacy and safety of IA in patients with CIDP with unsatisfactory response to first-line treatment options. Methods: CIDP patients received adjunct IA treatment using tryptophan-immune adsorbers. The inflammatory neuropathy cause and treatment disability (INCAT) score was used to grade disability and monitor treatment effects. Results: In total, 14 CIDP patients were analyzed. Ten patients were treated in hospital. After one IA treatment series, the INCAT score decreased significantly in all 10 patients. Four of these 14 patients were treated in outpatient clinics using long-term maintenance IA with 1–2 treatments per week. In these 4 patients, effects of long-term maintenance IA resulted in an improvement of overall disability. In all patients, IA was safe, well tolerated, and no severe adverse effects occurred. Conclusion: IA could be an effective and safe option for CIDP patients with unsatisfactory response to first-line treatment options and for long-term maintenance treatment.

The purpose of establishing the RheoNet registry was to evaluate the safety and efficacy of rheopheresis, a specific method of therapeutic apheresis used to treat microcirculatory disorders. Apheresis centers providing rheopheresis therapy and physicians caring for the underlying disease were asked to participate in the registry, and the registry data were analyzed for safety and tolerability. Age-related macular degeneration (AMD) was selected as a model disease to evaluate efficacy. The RheoNet registry was successfully established recording 7722 rheopheresis treatments of 1110 patients, including 833 AMD patients. The mean age of patients was 72 years. Adverse events (AE) were reported in 5.67% of treatments, but termination of the treatment session was only required in 0.48%. Transient hypotension was the most frequently reported AE. No age-related increase in AE was observed. Ophthalmological data of 428 eyes (of 279 treated patients) with dry AMD could be analyzed; 85 eyes of 55 untreated AMD patients served as the control. At 6.75 +/- 5.25 months post-baseline, 42% of the treated eyes had improved visual acuity. The proportion of eyes with a decline in visual acuity was 17%, compared to 40% in the untreated controls (P < 0.01). The RheoNet registry has been successfully established and data analysis revealed that rheopheresis is a safe outpatient treatment for microcirculatory disorders. Moreover, RheoNet currently provides the largest evaluation of the efficacy of rheopheresis for dry AMD. Registry analysis contributes to a safe and appropriate use of rheopheresis in clinical practice.

To evaluate Rheopheresis for the treatment of patients with high-risk dry age-related macular degeneration and no therapeutic alternative. Rheopheresis is a method of therapeutic apheresis using the methodology of double filtration plasmapheresis to treat microcirculatory disorders.The dry AMD treatment with Rheopheresis trial (ART) was a randomised, controlled clinical study. Patients with the diagnosis of AMD in both eyes, with the study eye presenting dry AMD and soft drusen (the fellow eye had advanced AMD) were randomly assigned in a 1:1 ratio to receive ten Rheopheresis treatments within 17 weeks or to remain untreated. The primary outcome was change in best-corrected ETDRS-visual acuity (mean logMar change) after 7.5 months compared to baseline visual acuity for both groups.Forty-three eyes of 43 patients (22 treatment and 21 control group) were analysed. The mean baseline BCVA in study eyes was 0.58 in the treatment group and 0.66 in the control group (n.s. p = 0.19). At the primary efficacy endpoint 7.5 months post baseline, there was a statistically significant mean difference of 0.95 ETDRS lines (p = 0.01) between the Rheopheresis and control groups. Nine percent of eyes in the group treated with Rheopheresis gained 2 or more ETDRS lines, as compared with 0% of eyes with no treatment. None of the treated patients had a loss in visual acuity in their study eyes, as compared with 24% of patients without treatment who lost 1 ETDRS line or more; 19% lost 2 ETDRS lines or more. Rheopheresis treatment was safe and well-tolerated.The results of ART provide further evidence that Rheopheresis is a safe and effective therapeutic option for high-risk patients with dry AMD and no therapeutic alternative. A series of Rheopheresis treatments can improve the natural course of AMD for selected patients.

Lipoprotein apheresis (LA) can lower LDL-cholesterol and Lp(a) by 60%-70% and is the final escalating option in patients with hyperlipoproteinemias involving LDL or Lp(a) particles. Major therapeutic effect of LA is preventing cardiovascular events. In Germany since 2008 a reimbursement guideline has been implemented accepting to establish the indication for LA not only for familial or severe forms of hypercholesterolemia but also based on Lp(a)-hyperlipoproteinemia associated with a progressive course of cardiovascular disease, that persists despite effective treatment of other concomitant cardiovascular risk factors. The Pro(a)LiFe-study confirmed with a prospective multicenter design that LA can be regarded as an important therapeutic approach to effectively reduce Lp(a) plasma levels and prevent cardiovascular events in this particular high-risk patient group. Results support that Lp(a) may be a major causal factor for precipitating mechanisms of accelerated progression of cardiovascular disease (CVD). Indication for LA based on measurement of Lp(a) as part of risk assessment is supported by the following conditions: progressive CVD as assessed clinically and with imaging techniques, established maximally tolerated lipid lowering drug treatment, recent cardiovascular events despite efficient drug treatment, out of the ordinary frequency of cardiovascular events, early CVD, or positive family history of early CVD. Still existing difficulties with Lp(a) laboratory measurement require a practical approach to establish the indication for LA considering the 60 mg/dl threshold of German guidelines with selecting an Lp(a) assay which has been calibrated for mass.

Extracorporeal low-density lipoprotein (LDL) apheresis is an established and highly effective therapy for patients with familial hypercholesterolemia (FH) not adequately responding to diet and drug therapy alone. Based on different methodology, five treatment options of LDL apheresis are available and in widespread practical use in Germany. All methods are safe and demonstrate equivalent efficacy of reducing LDL cholesterol with respect to the single apheresis session as well as during long-term treatment. Owing to methodological properties all methods also exhibit characteristics of additional plasma protein elimination, which do not impair, but in part, increase the beneficial therapeutic effect of LDL apheresis. Fibrinogen reduction has to be mentioned as an example. The lipidfiltration system is based on plasmafiltration previously named membrane differential filtration (MDF), synonymous with double filtration plasmapheresis (DFPP). The new term lipidfiltration was the result of technological progress leading to a significant improvement of the efficiency. The system consists of a novel lipid filter with enhanced sieving characteristics and capacity, and is completed by an enhanced therapy machine with an optimized heating unit.

The purpose of establishing the RheoNet registry was to evaluate the safety and efficacy of rheopheresis, a specific method of therapeutic apheresis used to treat microcirculatory disorders. Apheresis centers providing rheopheresis therapy and physicians caring for the underlying disease were asked to participate in the registry, and the registry data were analyzed for safety and tolerability. Age-related macular degeneration (AMD) was selected as a model disease to evaluate efficacy. The RheoNet registry was successfully established recording 7722 rheopheresis treatments of 1110 patients, including 833 AMD patients. The mean age of patients was 72 years. Adverse events (AE) were reported in 5.67% of treatments, but termination of the treatment session was only required in 0.48%. Transient hypotension was the most frequently reported AE. No age-related increase in AE was observed. Ophthalmological data of 428 eyes (of 279 treated patients) with dry AMD could be analyzed; 85 eyes of 55 untreated AMD patients served as the control. At 6.75 +/- 5.25 months post-baseline, 42% of the treated eyes had improved visual acuity. The proportion of eyes with a decline in visual acuity was 17%, compared to 40% in the untreated controls (P0.01). The RheoNet registry has been successfully established and data analysis revealed that rheopheresis is a safe outpatient treatment for microcirculatory disorders. Moreover, RheoNet currently provides the largest evaluation of the efficacy of rheopheresis for dry AMD. Registry analysis contributes to a safe and appropriate use of rheopheresis in clinical practice.

Patients suffering from sudden sensorineural hearing loss (SSHL), especially those with hearing impairment refractory to infusion therapy, need new therapeutic options. Fibrinogen-LDL-apheresis, covering Rheopheresis and HELP-apheresis for the indication of SSHL, proved to be an effective treatment option within the therapeutic armamentarium for SSHL in two randomized controlled trials including each more than 200 patients, and has also been shown to be an effective treatment option for patients refractory to the first line standard treatment. Fibrinogen-LDL-apheresis effects an immediate pulsed reduction of plasma viscosity as well as whole blood viscosity, hypothesized to lead to a sustained microcirculatory recovery, thus improving the natural course of acute microcirculatory impairment significantly. The solid body of evidence provided by investigations on fibrinogen-LDL-apheresis in recent years has been recognized by German SSHL guidelines, proposing fibrinogen-lowering treatments like this as part of a multimodality approach. Superiority of fibrinogen-LDL-apheresis over established first line standard treatments could not been shown in general. In consequence, no regular reimbursement by health insurances is available, in particular facing the current policy of health insurances for initial therapeutic nihilism at the acute onset of SSHL. Patients can apply for individual reimbursement or must pay the cost for the treatment. Refractory patients hopefully will profit by growing experiences.

There is increasing interest from neurologists to use therapeutic apheresis in autoimmune neurologic diseases due to growing knowledge of pathogenic relevance of autoantibodies. Developments in that field have been summarized in this review focusing on German guidelines and recent results from clinical research. Therapeutic apheresis can offer a therapeutic armamentarium with rapid response for severe acute neurologic symptoms, and a drug-free option for clinical courses being refractory to drug based strategies or complicated by drug side effects. Plasma exchange (PE) as the classical method has become part of current guidelines within basic and escalating immunomodulatory treatments of autoimmune neurologic diseases, and in daily practice gets increasingly replaced by selective immunoadsorption (IA) due to its equivalent efficacy in combination with a superior safety profile. Therapeutic effects of PE and IA in autoantibody mediated diseases can be attributed to 3 major mechanisms: immediate intravascular reduction of (auto-)antibody concentration, pulsed induction of antibody redistribution, and subsequent immunomodulatory changes. 5 treatments over a period of 8-10 days seem to be an appropriate regimen to restore neurologic function in acute flares or relapses of autoimmune neuropathies, e.g. myasthenic crisis, Guillain-Barre-syndrome, and steroid refractory relapse of multiple sclerosis. Especially in MS a better understanding is needed, who are the best candidates for IA.

Familial hypercholesterolemia (FH) not adequately responding to diet and drug therapy represents an indication for extracorporeal lipid-apheresis, which has become an highly effective and approved therapy for those patients in several countries. Based on different methodology, five treatment options of lipid-apheresis exist and are in widespread practical use covered by regular reimbursement in Germany. All methods are safe and demonstrate equivalent efficacy of reducing LDL cholesterol with respect to the single apheresis session as well as during long-term treatment. Therefore German reimbursement guidelines leave the choice of the method to the discretion of the apheresis center. Related to properties of the used technology all methods exhibit characteristic patterns of additional plasma protein elimination, which do not impair, but in part may increase the therapeutic benefit of lipid-apheresis. Fibrinogen reduction has to be mentioned as an example. The Lipidfiltration system is based on plasmafiltration previously referred to as membrane differential filtration (MDF), synonymous with double filtration plasmapheresis (DFPP). The new term Lipidfiltration was the result of technological progress in the manufacturing process of the plasmafilter resulting in enhanced sieving characteristics and capacity. The Lipidfiltration system is completed by a specifically designed therapy machine with optimised performance characteristics.

Age-related macular degeneration (AMD) is the leading cause of visual impairment and blindness in the elderly. Successful therapy is not yet available for the majority of patients, especially not for patients with dry AMD. AMD at cellular and molecular levels is at least in part a microcirculatory disorder of the retina. Rheopheresis is a safe and effective modality of therapeutic apheresis to treat microcirculatory disorders and represents a novel treatment option for patients with dry AMD. Elimination of a defined spectrum of high molecular weight proteins from human plasma including pathophysiologically relevant risk factors for AMD such as fibrinogen, cholesterol, von Willebrand factor, and alpha 2-macroglobulin results in the reduction of blood and plasma viscosity as well as erythrocyte and thrombocyte aggregation. Pulses of lowering blood and plasma viscosity performed as a series of Rheopheresis treatments lead to rapid changes of blood flow, subsequently inducing sustained improvement of microcirculation and recovery of retinal function. Two controlled randomized clinical trials demonstrated the safety and efficacy of Rheopheresis for the treatment of AMD patients, especially for those with the dry form. Recently the interim analysis of the sham-controlled, double blind, randomized multicenter Multicenter Investigation of Rheopheresis for AMD (MIRA-I) trial confirmed these results. The framework of completed and still ongoing controlled clinical trials in combination with postcertification studies including the RheoNet registry represents a comprehensive quality management approach for this novel interdisciplinary therapy for AMD. The development and continuous update of guidelines for the precise indication of Rheopheresis for AMD follows the requirements of evidence-based medicine.

Rheopheresis is a specific application of membrane differential filtration, synonymous with double filtration plasmapheresis for extracorporeal hemorheotherapy, eliminating an exactly defined spectrum of high molecular weight proteins from human plasma (e.g.: fibrinogen, alpha-2-macroglobulin, low-density lipoprotein cholesterol, IgM). This results in the improvement of blood flow and microcirculation initiated by lowering blood and plasma viscosity, and erythrocyte aggregation. In this context, microcirculation stands not only for the patency of small blood vessels, but for the complete interactive network between plasma, blood cells, the vessel wall, and cellular and extracellular compartments of the surrounding tissue. Insufficient tissue oxygenation leads to tissue damage, e.g., a microcirculatory disorder develops, creating acute as well as chronic symptoms. Therefore, impaired microcirculation has a rheologic, functional, and structural dimension with respect to involved organs or tissues. Rheopheresis represents a specific therapeutic approach with an acute rheologic as well as chronic functional and structural effects, which was confirmed in pilot and controlled clinical studies for several organ systems. Data from 2 controlled clinical trials are available for the safe and effective treatment in patients with age-related macular degeneration.

Purified histone H1 exerts growth inhibition of leukemia cells independent of lineage, stage, and maturation. At 200 micrograms/ml, H1 proved cytotoxic in 19 of 21 of the tested leukemia-derived cell lines and for 11 of 16 of the fresh tumor samples from leukemia patients. In all cases, normal peripheral blood mononuclear cells and bone marrow cells remained unaffected. Multicellular spheroids from the Burkitt's lymphoma cell line IM-9 were growth arrested at 500 micrograms H1/ml. The clonogenic growth of the Burkitt's lymphoma cell line Daudi was arrested at 160 micrograms H1/ml. Synthetic H1-peptides as well as peptides and proteins with biochemical properties similar to H1 had no inhibitory growth effect at equimolar concentrations. Furthermore, 250 micrograms H1 injected into a Burkitt's lymphoma (Daudi), xenotransplanted into nude mice, arrested tumor growth. As shown by electron microscopy and flow cytometry, incubation of leukemia cells with H1 resulted in severe plasma membrane damage and ultimately cytolysis. This report characterizes a 33-kd protein that binds H1 and is responsible for the cell death via destruction of the cell membrane integrity. New extranuclear functions of histones are presented.