Apheresis Centers Research Articles

Time from suspected thrombotic thrombocytopenic purpura to initiation of plasma exchange and impact on survival: A 10-year provincial retrospective cohort study

BackgroundThrombotic thrombocytopenic purpura (TTP) is a thrombotic microangiopathy (TMA) with significant morbidity and mortality. Guidelines recommend initiating plasma exchange within 4–8 h of suspected diagnosis. It is unclear what are real-world practice patterns and whether delays >8 h increases mortality. ObjectivesTo determine if delayed initiation of plasma exchange is associated with increased risk of death and complications. MethodsIn this retrospective cohort study, we evaluated the time from suspected diagnosis to plasma exchange in all adults presenting with suspected TTP to apheresis centres in Alberta, Canada (2008–2018). Among patients with acquired TTP, the association between delayed plasma exchange and risk of death was evaluated using Cox regression. ResultsOverall 190 episodes of suspected TTP were included among 163 individuals. Acquired TTP was confirmed in 61 patients. Inappropriate Emergency Department triage occurred in 59%. The median time from suspected diagnosis to first plasma exchange was 10.7 h; 59% had delayed plasma exchange >8 h, among whom plasma infusion was administered in only 45%. 36% of suspected TTP and 13% of confirmed TTP patients died. Delayed plasma exchange between 8 and 24 h was not associated with a significantly higher risk of death (adjusted hazards ratio; aHR 0.63, 95% CI 0.08–4.83) in confirmed TTP. On the other hand, the risks of death (aHR 1.40, 95% CI 0.20–9.79) and major thrombotic events (aHR 2.9, 95% CI 0.6–12.8) were markedly increased with >24 h delay. ConclusionsOur study demonstrated that TTP care in a real-world setting is discordant with expert guidelines due to multiple barriers. There is a gradient of increased mortality risk and thrombotic complications with longer treatment delays, although the study is likely underpowered.

Apheresis machines variably overestimate mononuclear cell collection volume.

Calculation of the actual number of CD34+ cells in the collection product is based on the volume of the collected product and its concentration of CD34+ cells measured in the lab. The number of CD34+ cells infused correlates closely with the pace of hematopoietic reconstitution following autologous or allogeneic stem cell transplantation. We studied peripheral blood stem cell collections in a single apheresis center with two Spectra Optia devices, using mononuclear cell collection or continuous mononuclear cell collection procedures. The collection volume displayed by the apheresis device was compared with the volume determined by a weight-based method. Fifty-two consecutive CD34 collections in 35 different donors (range 1-4 daily procedures per donor) were analyzed. The machines reported larger collection volumes (P < .001). The mean collection volume reported by the machine was 274.37 mL (range 162-396). The mean manually measured collection volume was 261.82 mL (range 155-371.40). Mean overestimation by machine was 12.53 mL (range -0.95 to 31.24; 95% confidence interval 10.94-14.11) or 4.88% (range -0.26 to 10.28). Median overestimation of the absolute number of CD34 was 10.29 × 106 (range -2.83 to 141.84 × 106 ). Both Spectra Optia machines overestimated the collection volume after peripheral blood stem cell collection. Although the mean variation falls within the expected range, in some cases, this overestimation may be clinically relevant if no other method of measurement is used.

Long-term lipoprotein apheresis in the treatment of severe familial hypercholesterolemia refractory to high intensity statin therapy: Three year experience at a lipoprotein apheresis centre.

Severe familial hypercholesterolemia (FH) individuals, refractory to conventional lipidlowering medications are at exceptionally high risk of cardiovascular events. The established therapeutic option of last choice is lipoprotein apheresis (LA). Herein, it was sought to investigate the clinical usefulness of LA in a highly selected group of severe heterozygous FH (HeFH), as recently described by the International Atherosclerosis Society (IAS), for their efficacy in lipid reduction and safety. Efficacy and safety of LA were investigated in 318 sessions of 7 severe HeFH females with cardiovascular disease, over a mean period of 26.9 ± 6.5 months. Relative reduction of low density lipoprotein cholesterol (LDL-C) ≥ 60%, clinical complications and vascular access problems were evaluated and compared between the direct adsorption of lipoproteins (DALI) and lipoprotein filtration (Membrane Filtration Optimized Novel Extracorporeal Treatment [MONET]). Additionally, lipoprotein (a) [Lp(a)], total cholesterol (TC), high density lipoprotein cholesterol (HDL-C), triglycerides (TG) and fibrinogen concentrations were investigated. The relative reduction of LDL-C, TC, TG and Lp(a) were 69.4 ± 12.9%, 59.7 ± 9.1, 51.5 ± ± 14.2% and 71.3 ± 14.4%, respectively. A similar efficacy was found in both systems in LDL-C removal. DALI system led to larger depletions of Lp(a) (80.0 [76-83]% vs. 73.0 [64.7-78.8]%; p < 0.001). The frequency of clinical side effects and vascular access problems were low (8.5%). Long-term LA in severe HeFH individuals is safe and efficiently reduces LDL-C and Lp(a). Higher efficacy of the DALI system than MONET in Lp(a) removal may indicate the need for individualized application of the LA system in severe HeFH individuals.

The effect of DALI lipid apheresis in the prognosis of homozygous familial hypercholesterolemia: Seven patients' experience at a DALI apheresis center.

Introduction:Familial hypercholesterolemia (FH) is characterized by severe hypercholesterolemia that can result in coronary artery disease occurring at an early age. If patients are not cured with lipid-lowering drugs and diets, lipid apheresis may be an effective treatment option in these cases. Here, we evaluate the efficacy, selectivity and safety of the DALI apheresis technique.Materials and Methods:Seven pediatric patients (2 girls; 5 boys) with ages between 7 and 14 years (mean age: 6.5±2.1 years) with HFH were included in this study. We restrospectively evaluated clinical and laboratory findings. We used the DALI system for lipid apheresis concomitant with medical treatment and diet for hyperlipidemia.Results:The cohort's mean T.cholesterol level prior to apheresis was 700.57±136.36 mg/dl,the mean LDL-C value was 526.86±131.56 mg and the mean HDL-C level was 36.57±4.58 mg/dl.The mean cholesterol levels after apheresis were consecutively 317.57±93.70 /257.29±90.38 / 33.36±4.78 mg/dl.We noted a 51.1% reduction in LDL-C level and an 8.7% reduction in HDL-C level in our apheresis sessions.The reduction in LDL-C was statistically significant (p<0.05). During 1025 apheresis therapy, the most frequent mild and moderate adverse events were deviceaccess problems and hypotension (in all patients);severe adverse events were mainly due to cardiac problems(myocardial infarct and arrhythmia) and hypotension.Conclusion:Lipid apheresis is an inevitable alternative treatment for HFH. Despite all of its application problems, DALI system is an effective therapy for decreasing atherogenic lipids from circulation.

Validation of the Plasmic Score for Predicting ADAMTS13 Activity < 10% in Patients Admitted to Hospitals in Alberta with Suspected Thrombotic Thrombocytopenic Purpura

Thrombotic thrombocytopenic purpura (TTP) is a life-threatening thrombotic microangiopathy (TMA), characterized by widespread intravascular thrombosis. Diagnosis of TTP is confirmed by a deficiency in ADAMTS13. However, given the urgency of prompt diagnosis and delayed turnaround time of ADAMTS13 assay in most labs, initial diagnosis is based on clinical acumen. Suspected TTP is empirically treated with plasma exchange (PLEX), which, while beneficial in TTP, may delay appropriate treatment for similar disorders. The PLASMIC score was developed by Bendapudi et al. (Lancet Hematology 2017) to utilize clinical signs and investigations to predict which patients had an ADAMTS13 score &lt; 10%, and therefore TTP, who require PLEX. Validation studies have shown a very high sensitivity (90-98%) and high specificity (46-92%), although these studies included an enriched population with available ADAMTS13 assay results (Jajosky et al. Transfusion and Apheresis Science, 2017, Li et al. Journal of Thrombosis and Hemostasis 2018). The purpose of this study is to validate the PLASMIC score using a Canadian population of suspected TTP regardless if ADAMTS13 was ordered, and compare it to clinical gestalt. This is a retrospective cohort study of all adults aged 18 years or older who presented or were transferred to any of the two apheresis centres in Alberta, Canada with a suspected diagnosis of TTP from January 1, 2008 - December 31, 2018. A confirmed diagnosis of TTP was defined as an ADAMTS13 level prior to PLEX &lt; 10%, or ADAMTS13 level between 10-20% if drawn after plasma infusion or PLEX. ADAMTS13 testing was done in accordance with the procedures at these institutions. The PLASMIC score was used to stratify patients into low (0-4), intermediate (5) and high (6-7) risk of TTP (Table 1). Descriptive analyses was performed to examine the proportion of patients with low-, intermediate-, and high-risk PLASMIC score who had ADAMTS13 testing done and who received PLEX. The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of PLASMIC score were calculated. Two PLASMIC score cutoffs were used for the analysis, 1) high risk vs low to intermediate risk, and 2) intermediate to high risk vs low risk. Receiver operator curve (ROC) analysis was used to test the association between severe ADAMTS13 deficiency and the PLASMIC score. PLASMIC scores were also compared to clinical gestalt, defined as initiation of PLEX within 48 hours of presentation. The C statistic was calculated from the area under the ROC and compared using the Z-test. As some patients who may have died from TTP did not have ADAMTS13 level sent, sensitivity analysis was performed to assess the ROC curve for the PLASMIC score in detecting both definite and probable TTP. A P-value of &lt;0.05 was considered statistically significant. Of the 162 cases of suspected TTP, 61 (38%) had severe ADAMTS13 &lt;10%. ADAMTS13 was sent prior to plasma exchange in 103 (64%) cases and shortly after PLEX initiation in 15 (9%). Using a high-risk PLASMIC score cut-off (6-7) vs low to intermediate-risk score (0-5), the sensitivity was 83.6%, specificity 67.3%, PPV 60.7% and NPV 87.2%. In contrast, using a cut-off of medium to high-risk PLASMIC score (5-7) vs low-risk score (0-4), the sensitivity improved to 96.7%, whereas the specificity was reduced to 30.7% (PPV 45.7% and NPV 93.9%). The C-statistics were 0.75 (95% CI 0.69-0.82) and 0.64 (95% CI 0.59-0.69) using the high PLASMIC score and medium-high PLASMIC score cut-offs, respectively (Figure 1). In contrast to PLASMIC score-based risk stratification, clinical gestalt has a comparable sensitivity of 83.6%, but a much lower specificity of 38.9%. There was very low correlation between PLASMIC score and clinical gestalt (kappa 0.0883 (95% CI -0.03-0.21). In our cohort, a high-risk PLASMIC score successfully predicted patients with severe ADAMTS13 deficiency in a Canadian TMA population, with similar sensitivity and improved specificity compared to clinical gestalt. Integration of this scoring system into institutional clinical pathways should be considered to supplement clinician judgment and reduce costs. Disclosures No relevant conflicts of interest to declare.

Apheresis For Elevated Lipoprotein(A) In The Us, A Nationwide Survey Of Apheresis Centers In The United States

Background and Aims: Apheresis for treatment of patients with elevated Lipoprotein(a) {Lp(a)} with Coronary Artery Disease (CAD) and is commonly employed in Germany, other European countries, Russia and UK.

A Study on Influence of Donor Hematocrit on the Procedural Parameters of Concentrated Single Donor Platelets Collected by Two Apheresis Devices.

With improvements in apheresis collection, platelet additive solution (PAS) is steadily replacing plasma as the storage medium in single donor platelets (SDP). Concentrating platelets in SDP with one-third of plasma and two-thirds of PAS is referred as Concentrated-SDP (C-SDP). We studied the influence of donor hematocrit (Hct) in C-SDP procedures. A retrospective study, consisting of 124 and 95 plateletpheresis donors in MCS+ and Trima respectively. We compared two apheresis equipments MCS+ and Trima with regard to donor hematocrit on procedural parameters such as collection efficiency (CE), collection rate (CR), yield per hour (Y/H), yield per litre (Y/L) and percentage blood volume processed (%BV) during C-SDP procedures. Donors were categorized into two groups with Group A (Hct ≤ 46%) and Group B (Hct > 46%) based on mean baseline Hct of the study population. Among the 219 procedures, the overall CE was significantly higher for Trima over MCS+ equipment (77 vs 56, P < 0.001). However, there was no difference in procedural outcomes like CE, Y/L, Y/H, CR with MCS+ or Trima equipment between groups. %BV processed had a negative correlation with hematocrit in MCS+ (r = - 0.305, P = 0.001) and no difference was observed with Trima equipment. Donor Hct influences C-SDP collection only in processed blood volume with MCS+ equipment. Trima had statistically better performance over MCS+ equipments in all procedural parameters during C-SDP procedures. The data will guide apheresis centre to choose equipments based on donor characteristics.

Validation of an Apheresis Collection Prediction Algorithm for Hematopoietic Progenitor Cells Using the Spectra Optia Cmnc Protocol

Background Increased emphasis on cost and productivity in apheresis centers requires proficient and predictable hematopoietic progenitor cell (HPC) collections. The aim of this study was to compare pre and post collection outcomes utilizing a customized prediction algorithm to estimate the number of blood volumes required to achieve a targeted CD34+ cell dose. Methods A prediction algorithm was determined by utilizing the collection efficiency from 19 autologous patients with 26 collections on the Spectra Optia CMNC from October 2017 through March 2018. The algorithm was based upon the linear regression of pre-apheresis CD34 counts, the collected CD34 cell dose and blood volumes processed. Validation was performed on 21 HPC collections (18 auto, 3 allo) completed from June 2018 through September 2018. In the analysis, if a patient collected more than one day, the data from each procedure was combined in the analysis. Cohort A included collections prior to implementation of the prediction algorithm and Cohort B included collections after implementation of the prediction algorithm. T-Test statistical analysis was used for variables that were normally distributed and Mann-Whitney statistical analysis was used for variables that were not normally distributed. Results Following implementation of the algorithm, the mean number of collections per patient decreased from 1.3 to 1.0 (P=0.003) and mean procedure time decreased from 376 minutes to 305 minutes (P=0.002). In addition, number of liters processed per patient was lower, 24.3 vs. 21.3 (P=0.466) and the product volume decreased from 348ml to 286ml (P=0.011). Product hematocrit, collection efficiency and product CD34+ yield were not significantly different. Pre procedure WBC and hematocrit were similar in each group, but platelet counts were significantly lower in Cohort A, likely due to donors requiring multiple days of collection. All patients engrafted. Discussion This analysis demonstrates that using a prediction algorithm can provide great value in the planning of leukapheresis, which may optimize resource utilization and capacity of the unit while maintaining the ability to collect the desired stem cell goal. Decreasing donor procedure time and number of days of collection prevents over collecting and further enhances donor safety. In addition, predictability was facilitated by a proficient and consistent performance of the Spectra Optia CMNC. Further investigation should include plerixafor use, cost analysis and impact on product storage.

Therapeutic plasmapheresis in thyrotoxic patients.

For the treatment of thyrotoxicosis, alternative treatment modalities may be necessary if anti-thyroid drugs cannot be used due to side effects, inefficiencies, or there is a need to start a rapid action such as thyroid storm. By using therapeutic plasma exchange (TPE), it is possible to effectively and rapidly remove the increased thyroid hormones. We evaluated our results and experience on a rapid, effective, and reliable alternative treatment modality in thyrotoxic patients. TPE was performed in 46 thyrotoxic patients at the Adult Therapeutic Apheresis Center. Forty six patients with a median age of 30 years (interquartile range [IQR] 30-50) were assessed. In 40 (87%) of the cases, the diagnosis was Graves' disease. The other causes of thyrotoxicosis were amiodarone-induced thyrotoxicosis (n = 4) and toxic nodular goiter (n = 2). The median and IQR of fT3 values in patients before TPE were 9.9 (6.5-16.8) pg/mL (N: 2.3-4.2) and the median and IQR of fT4 values were 2.9 (2.3-4.1) ng/dL (N: 0.74-1.52). When the procedure was terminated, the median and IQR of fT3 values in patients were 4.0 (3.1-5.2) pg/mL and the median and IQR fT4 values were 1.6 (1.4-2.0) ng/dL. The decrease in both free thyroid hormones was found to be statistically significant (p < 0.000). Our study is the largest series of TPE in the literature used for thyrotoxicosis. In the light of the literature and our results, we conclude that TPE is an effective alternative treatment option to prepare for ablative treatment for cases that have side effects or ineffectiveness of anti-thyroid drugs.

Peripheral blood stem cell mobilisation with G-CSF alone versus G-CSF and cyclophosphamide after bortezomib, cyclophosphamide and dexamethasone induction in multiple myeloma.

Bortezomib-based induction is often used in transplant-eligible patients with myeloma. The optimal peripheral blood stem cell (PBSC) mobilisation strategy in this context is unclear. We reviewed the efficacy of G-CSF alone (G-alone) vs. G-CSF and cyclophosphamide (G-cyclo: standard dose: 1.5-2 g/m2; high dose: 3-4 g/m2) PBSC mobilisation strategies in 288 patients who only received bortezomib, cyclophosphamide and dexamethasone (VCD) induction prior to autograft across six apheresis centres from November 2012 to June 2017. 'Uncomplicated successful mobilisation' was defined as achieving a PBSC yield of ≥4 × 106/kg within two aphereses, without plerixafor or mobilisation-associated toxicity (predominantly febrile neutropenia, FN). Success rates were 84% in G-cyclo standard dose (6% FN), 64% in G-cyclo high dose (18% FN) and 69% in G-alone (plerixafor successfully salvaged 8/9 patients). Median total stem cell yield was significantly higher with G-cyclo, but not different between the two cyclophosphamide doses. Age greater than the median of 61 years was associated with higher failure rates (22 vs. 11%, p = 0.01) and lower PBSC yield, especially in the G-alone group. Prior radiotherapy exposure did not impact on collection success. Our observations suggest that both G-cyclo standard dose and G-alone are reasonable mobilisation strategies. The former may be preferred if salvage plerixafor is unavailable.

Reduction of peripheral blood stem cell collection sessions with extended-hour operation of the apheresis center

Reduction of peripheral blood stem cell collection sessions with extended-hour operation of the apheresis center

A multicenter experience of thrombotic microangiopathies in Turkey: The Turkish Hematology Research and Education Group (ThREG)-TMA01 study

Thrombotic microangiopathies (TMAs) are rare, but life-threatening disorders characterized by microangiopathic hemolytic anemia and thrombocytopenia (MAHAT) associated with multiorgan dysfunction as a result of microvascular thrombosis and tissue ischemia. The differentiation of the etiology is of utmost importance as the pathophysiological basis will dictate the choice of appropriate treatment.We retrospectively evaluated 154 (99 females and 55 males) patients who received therapeutic plasma exchange (TPE) due to a presumptive diagnosis of TMA, who had serum ADAMTS13 activity/anti-ADAMTS13 antibody analysis at the time of hospital admission. The median age of the study cohort was 36 (14-84). 67 (43.5%), 32 (20.8%), 27 (17.5%) and 28 (18.2%) patients were diagnosed as thrombotic thrombocytopenic purpura (TTP), infection/complement-associated hemolytic uremic syndrome (IA/CA-HUS), secondary TMA and TMA-not otherwise specified (TMA-NOS), respectively. Patients received a median of 18 (1­75) plasma volume exchanges for 14 (153) days. 81 (52.6%) patients received concomitant steroid therapy with TPE. Treatment responses could be evaluated in 137 patients. 90 patients (65.7%) achieved clinical remission following TPE, while 47 (34.3%) patients had non-responsive disease. 25 (18.2%) non-responsive patients died during follow-up. Our study present real-life data on the distribution and follow-up of patients with TMAs who were referred to therapeutic apheresis centers for the application of TPE.

Vascular access in lipoprotein apheresis: a retrospective analysis from the UK's largest lipoprotein apheresis centre.

Lipoprotein apheresis (LA) has proven to be an effective, safe and life-saving therapy. Vascular access is needed to facilitate this treatment but has recognised complications. Despite consistency in treatment indication and duration there are no guidelines in place. The aim of this study is to characterise vascular access practice at the UK's largest LA centre and forward suggestions for future approaches. A retrospective analysis of vascular access strategies was undertaken in all patients who received LA treatment in the low-density lipoprotein (LDL) Apheresis Unit at Harefield Hospital (Middlesex, UK) from November 2000 to March 2016. Fifty-three former and current patients underwent 4260 LA treatments. Peripheral vein cannulation represented 79% of initial vascular access strategies with arteriovenous (AV) fistula use accounting for 15%. Last used method of vascular access was peripheral vein cannulation in 57% versus AV fistula in 32%. Total AV fistula failure rate was 37%. Peripheral vein cannulation remains the most common method to facilitate LA. Practice trends indicate a move towards AV fistula creation; the favoured approach receiving support from the expert body in this area. AV fistula failure rate is high and of great concern, therefore we suggest the implementation of upper limb ultrasound vascular mapping in all patients who meet treatment eligibility criteria. We encourage close ties between apheresis units and specialist surgical centres to facilitate patient counselling and monitoring. Further prospective data regarding fistula failure is needed in this expanding treatment field.

The management of anticoagulation in patients undergoing therapeutic plasma exchange: A concise review.

We surveyed multiple apheresis centers represented by the authors for their clinical approach to the management of anticoagulation issues during therapeutic plasma exchange (TPE). We present the results of their practices and a review of the pertinent literature. As plasma is removed during TPE, replacement with all or partial non-plasma-containing fluids (eg, 5% albumin) may lead to significant changes in hemostasis. These changes are amplified in patients who are receiving anticoagulation. We discuss various anticoagulants as well as the monitoring and adjustment of anticoagulation before, during, and after TPE. No single guideline can be applied, but rather, patients must be monitored individually, taking into account their often complex clinical conditions and medication profiles.

Most significant reduction of cardiovascular events in patients undergoing lipoproteinapheresis due to raised Lp(a) levels – A multicenter observational study

ObjectivesLipoprotein(a) (Lp(a)) is an independent cardiovascular (CV) risk factor, predisposing to premature and progressive CV events. Lipoproteinapheresis (LA) is the only efficacious therapy for reducing Lp(a). Data comparing the clinical efficacy of LA with respect to reduction of CV events in subjects with elevated Lp(a) versus LDL-C versus both disorders is scarce. We aimed to perform this comparison in a multicenter observational study. Methods113 LA patients from 8 apheresis centers were included (mean age 56.3 years). They were divided into 3 groups: Group I: Lp(a) < 600 mg/l, LDL-C > 2.6 mmol/l, Group II: Lp(a) > 600 mg/l, LDL-C < 2.6 mmol/l, and Group III: Lp(a) > 600 mg/l, LDL-C > 2.6 mmol/l. CV events were documented 2 years before versus 2 years after LA start. ResultsBefore start of LA Group II showed the highest CV event rate (p 0.001). Group III had a higher CV event rate than Group I (p 0.03). During LA there was a significant reduction of CV events/patient in all vessel beds (1.22 ± 1.16 versus 0.33 ± 0.75, p < 0.001). The highest CV event rate during LA was seen in coronaries followed by peripheral arteries, cerebrovascular events were least common. Greater CV event reduction rates were achieved in patients with isolated Lp(a) elevation (−77%, p < 0.001) and in patients with Lp(a) and LDL-C elevation (−74%, p < 0.001) than in subjects with isolated hypercholesterolemia (−53%, p 0.06). ConclusionThis study demonstrates that patients with Lp(a) elevation benefit most from LA treatment. Prospective trials to confirm these data are warranted.

Low rate of infectious complications following immunoadsorption therapy without regular substitution of intravenous immunoglobulins

IntroductionImmunoadsorption (IA) is increasingly used instead of plasma exchange due to lower risk of side effects and a higher selectivity. As a consequence of the reduction of immunoglobulins (Ig), the rate of infectious complications might increase in those patients. We therefore aimed to investigate the infection rate following IA without intravenous IG (IVIG) substitution in our apheresis center, where patients do not receive IVIG on a regular basis. Material and methodsWe conducted a retrospective analysis of the IA treatments performed between 2010 and 2015 without IVIG substitution and collected data on patient age, diagnosis, number of IA treatments, serum levels of Ig, total protein, albumin, C-reactive protein (CRP) and infectious complications that occurred within 2 months after the IA treatment cycle. ResultsA total number of 52 patients (27 females) received at least 5 IA sessions using the following adsorbers: TheraSorb™-Ig (n = 3), TheraSorb™-Ig flex (n = 44), TheraSorb™ Ig pro (n = 1) and TheraSorb™-IgE (n = 5). The median number of treatment sessions was 8.8 [range 5–16], the median IgG reduction was 82 [11–99] %. Serum albumin was decreased by 8%. The median CRP levels remained normal until the end of therapy and within 2 months after that (3.10 and 4.30 mg/L respectively). Only 4 patients had infections (7.7%). Three of them received additional immunosuppressive therapy. ConclusionsImmunoadsorption leads to a significant reduction of IgG. CRP as inflammatory marker is not affected. Even without substitution of IVIG the complication rate directly linked with IA is low and questionable.

History of lipidology and lipoprotein apheresis

This review tells the story of atherosclerosis research in the beginning of the 20th century. It presents the significance of cardiovascular diseases and addresses major questions currently being discussed among lipidologists and the current thinking with respect to low LDL-cholesterol levels and HDL. It provides an overview of the period during which lipid-modifying drugs were introduced and their relevance with respect to cardiovascular outcome data and lists possible reasons why some patients develop new cardiovascular events while being treated with statins. Especially impressive is the history of the appearance of the PCSK9 inhibitors on the market – only 12 years after PCSK9 was detected; a study completed in 2017 provides evidence about the cardiovascular effects of these new drugs. Other new drugs are also mentioned: mipomersen, lomitapide, and Alipogen Tiparvovec. Some promising drugs are still in the pipeline which inhibit the synthesis of apolipoprotein CIII, apolipoprotein(a), and the PCSK9 protein. During the 1970s, specific lipoprotein apheresis began to be used in high-risk patients with homozygous familial hypercholesterolemia, severe hypercholesterolemia and elevated Lipoprotein(a) levels and this review provides evidence of the effectiveness of the extracorporeal therapy with respect to the reduction of cardiovascular events. Particularly in patients with high Lipoprotein(a) levels, apheresis has been proven capable of reducing cardiovascular events by more than 80%. The current situation with regard to lipoprotein apheresis centers and patients in Germany is described herein, and, in conclusion, an estimation of the future of the therapeutic options in lipidology is given.

How effectively will PCSK9 inhibitors allow retrieval of freedom from apheresis in cardiovascular high risk patients? – Estimates form a large single center

Lipoprotein apheresis (LA) has been the last-resort therapeutic option in patients suffering from limited pharmaceutical options to lower highly elevated low density lipoprotein cholesterol (LDL-C) levels. Facing the introduction of the proprotein convertase subtilisin/kexine type 9 (PCSK-9) inhibitors, it has been speculated that they might replace LA to a large extend. Given an efficacy of approx. 55–65% to lower LDL-C it is important to analyze whether this might be realistic i) for potential candidates in apheresis sites and ii) for the future structures of the sites themselves.We performed a review of our own single center, one of the largest apheresis centers in Germany to answer these questions. Therefore we analyzed all actively treated apheresis patients and identified those with the primary indication of LDL-C elevation. In a next step we used pre-apheresis LDL-C values to calculate expected LDL-C under three given models of PCSK9 inhibitor efficacy.Including other aspects such as the accompanying presence of elevated lipoprotein(a), we identified 11–17 patients among 29 patients undergoing treatment for insufficiently treated LDL-C (38–58%). In the total cohort of 112 patients this reflects 10–15% of all patients that might potentially stop apheresis therapy due to the availability of PCSK9 inhibitor therapy, which is in clear contrast to speculations on the future perspective of apheresis therapy.

Current insights into the German Lipoprotein Apheresis Registry (GLAR) – Almost 5 years on

BackgroundIn recent years the Federal Joint Committee (G-BA), a paramount decision-making body of the German health care system required a reassessment of the approval of chronic lipoprotein apheresis therapy for regular reimbursement. Since 2005 an interdisciplinary German apheresis working group has been established by members of both German Societies of Nephrology. In 2009 the working group completed the indication for lipoprotein apheresis with respect to current cardiovascular guidelines and current scientific knowledge for the registry. In 2011 the German Lipoprotein Apheresis Registry (GLAR) was launched and data acquired over nearly 5 years can now be reported. Methods and resultsAll data were collected and analyzed during the time period 2012–2015. Over this time interval, 68 German apheresis centers collected retrospective and prospective observational data of 1.283 patients undergoing lipoprotein apheresis (LA) treatment of high LDL-cholesterol (LDL-C) levels and/or high lipoprotein(a) (Lp(a)) levels suffering from progressive cardiovascular disease (CVD). A total of 15,167 documented LA treatments were investigated. All patients treated by LA exhibited a median LDL-C reduction rate of 68.6%, and a median Lp(a) reduction rate of 70.4%. Analogue to the Pro(a)LiFe pattern, patient data were analyzed and compared with respect to the incidence rate of coronary events (MACE) 1 and 2 years before the start of LA treatment (y−2 and y−1) and prospectively one year on LA treatment (y+1). During the first year of LA treatment a MACE reduction of 97% was be observed. In the years considered, LA treatment side effects occurred at a low rate (ca. 5%) and mainly comprised puncture problems. ConclusionsFor the first time data generated by the GLAR shows that LA lowers the incidence rate of cardiovascular events in patients with high LDL-C and/or high Lp(a) levels, progressive CVD and maximally tolerated lipid lowering medication. In addition LA treatments were found to be safe, exhibiting a low rate of side effects.

161 - Safety, clinical efficancy, and cost-effectiveness of mononuclear cell collections for autologous immunotherapies: First experience from a private cell collection facility

Background & Aim Within the EU the collection of mononuclear cells (MNC) as starting source for the manufacturing of autologous cell therapies are mainly performed in hospitals or hospital-associated apheresis centers. We report about the challenges to perform the leukapheresis procedure (LA) at a private held medical practice, with specific emphases on safety, cell collection efficiency, and cost-effectiveness. Methods, Results & Conclusion We reviewed the records of altogether 60 outpatients and 100 healthy donors who underwent a total of 220 unstimulated LA procedure at Cyto-Care, a private held medical practice/ certified cell collection facility located in Vienna, Austria. All patients participated in various industry-sponsored clinical P I-III trials; the study sponsors were responsible for the manufacturing of the active cell product. Disease entities were mainly prostatic cancer (75%) and ovarian cancer (20%). Based on differences in the study protocols LA was performed either one-time (41%), two-times (27%) or three-times (32%), with an interval of at least 2 weeks between repeated collections. All patients successfully completed the apheresis course. Because of poor venous access, 3 out of 60 patients (5%) required a short-term femoral catheter insertion. There were no serious side effects in patients who required a femoral catheter, or in patients with repeated LA procedures. Side effects of the LA procedure mainly consisted on mild hypocalcaemia-related symptoms in 16% of patients. A follow-up survey one week after completion of the LA revealed no infectious complications, and no patient required hospitalization. Median cell yield collected per single apheresis was 1.5 × 10e10 WBC consisting of 1.3 × 10e10 MNC. MNC cell yields remained stable even in repeated LA collections. All cell products were successful transformed into an active cellular product. Analysis of the cost structure showed that the total cost of care was 32% lower in the setting of a private collection center compared to hospital-based apheresis centers. Leukapheresis performed in a private medical practice/ certified cell collection facility is safe and effective, with low rates of complications and high levels of patient satisfaction. This service model is cost-effective and can help to reduce the cost of manufactured goods in the production of innovative cellular products.