The world apheresis association registry, 2023 update.

The WAA apheresis registry contains data on more than 140,000 apheresis procedures conducted in 12 different countries. The aim is to give an update of indications, type and number of procedures and adverse events (AEs). MATERIAL AND METHODS: The WAA-registry is used for registration of apheresis procedures and is free of charge. The responsible person for a center can apply at the site www.waa-registry.org RESULTS: Data includes reported AEs from 2012 and various procedures and diagnoses during the years 2018-2022; the latter in total from 27 centers registered a total of 9500 patients (41% women) that began therapeutic apheresis (TA) during the period. A total of 58,355 apheresis procedures were performed. The mean age was 50 years (range 0-94). The most common apheresis procedure was stem cell collection for which multiple myeloma was the most frequent diagnosis (51%). Donor cell collection was done in 14% and plasma exchange (PEX) in 28% of patients; In relation to all performed procedures PEX, using a centrifuge (35%) and LDL-apheresis (20%) were the most common. The main indication for PEX was TTP (17%). Peripheral veins were used in 56% as the vascular access. The preferred anticoagulant was ACD. AEs occurred in 2.7% of all procedures and were mostly mild (1%) and moderate 1.5% (needed supportive medication) and, only rarely, severe (0.15%). CONCLUSION: The data showed a wide range of indications and variability in apheresis procedures with low AE frequency.

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.

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.

Comparison of plasma separation using centrifugation or filtration for MONET lipoprotein apheresis in patients with cardiovascular disease and severe dyslipidemia.

INTRODUCTION: Homozygous or severe heterozygous familial hypercholesterolemia and elevated lipoprotein(a) levels may be treated with membrane filtration. The MONET system (Fresenius Medical Care, Bad Homburg, Germany) involves plasma separation by centrifugation or filtration. METHODS: Whether the method of plasma separation affects lipoprotein lowering and treatment safety was investigated in a single-center retrospective study. RESULTS: The centrifugation-based plasma separation achieved a higher plasma flow and shorter time to treat 1 L of plasma (46.2 ± 8.6 min), than the filtration-based system (71.5 ± 40.0 min; p = 0.001). The mean reduction of LDL-cholesterol was 69% and 67% with centrifugation and filtration and was 75% for lipoprotein(a) with both plasma separation methods. A reduction of IgM by more than 60%, of albumin and total protein by approximately 20% and low frequency of side effects was observed. CONCLUSIONS: The efficacy of lowering atherogenic lipoproteins was comparable with both plasma separation methods. Centrifugation was more time-efficient compared to filtration.

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.

Pathogenic classification of LPL gene variants reported to be associated with LPL deficiency.

BACKGROUND: Lipoprotein lipase (LPL) deficiency is a serious lipid disorder of severe hypertriglyceridemia (SHTG) with chylomicronemia. A large number of variants in the LPL gene have been reported but their influence on LPL activity and SHTG has not been completely analyzed. Gaining insight into the deleterious effect of the mutations is clinically essential. METHODS: We used gene sequencing followed by in-vivo/in-vitro and in-silico tools for classification. We classified 125 rare LPL mutations in 33 subjects thought to have LPL deficiency and in 314 subjects selected for very SHTG. RESULTS: Of the 33 patients thought to have LPL deficiency, only 13 were homozygous or compound heterozygous for deleterious mutations in the LPL gene. Among the 314 very SHTG patients, 3 were compound heterozygous for pathogenic mutants. In a third group of 51,467 subjects, from a general population, carriers of common variants, Asp9Asn and Asn291Ser, were associated with mild increase in triglyceride levels (11%-35%). CONCLUSION: In total, 39% of patients clinically diagnosed as LPL deficient had 2 deleterious variants. Three patients selected for very SHTG had LPL deficiency. The deleterious mutations associated with LPL deficiency will assist in the diagnosis and selection of patients as candidates for the presently approved LPL gene therapy.

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.

Comparison of two filter combinations for low-density lipoprotein apheresis by membrane differential filtration: a prospective crossover controlled clinical study.

Membrane differential filtration is an accepted procedure for the extracorporeal removal of low-density lipoprotein (LDL). Reduction rates largely depend on the nature of the membranes and are ideally evaluated in a crossover study design. Four patients who had been treated by LDL apheresis for at least 6 months were included. Six consecutive weekly sessions (40 ml plasma/kg body weight) were scheduled per system (Plasmacure PS06/Evaflux Eval 5A [Kuraray] versus Plasmaflo OP05W/Cascadeflo AC1770 [Asahi]). Laboratory measurements indicated reductions of plasma concentrations for fibrinogen (37% [Kuraray] versus 44% [Asahi]), IgG (15% versus 20%), IgA (24% versus 28%), IgM (63% versus 53%), and total protein (11% versus 16%). Total cholesterol was eliminated by 52% versus 49%, LDL by 67% versus 66%, triglycerides by 56% versus 41%, and high-density lipoprotein by 10% versus 20%. Three therapies employing the Asahi filter combination were terminated prematurely due to saturation of the plasma fractionator. In conclusion, despite similar physical properties, the membranes differ significantly concerning selectivity and sensitivity to saturation.