One-year follow-up of the CAPSID randomized trial for high-dose convalescent plasma in severe COVID-19 patients.

BACKGROUNDResults of many randomized trials on COVID-19 convalescent plasma (CCP) have been reported, but information on long-term outcome after CCP treatment is limited. The objectives of this extended observation of the randomized CAPSID trial are to assess long-term outcome and disease burden in patients initially treated with or without CCP.METHODSOf 105 randomized patients, 50 participated in the extended observation. Quality of life (QoL) was assessed by questionnaires and a structured interview. CCP donors (n = 113) with asymptomatic to moderate COVID-19 were included as a reference group.RESULTSThe median follow-up of patients was 396 days, and the estimated 1-year survival was 78.7% in the CCP group and 60.2% in the control (P = 0.08). The subgroup treated with a higher cumulative amount of neutralizing antibodies showed a better 1-year survival compared with the control group (91.5% versus 60.2%, P = 0.01). Medical events and QoL assessments showed a consistent trend for better results in the CCP group without reaching statistical significance. There was no difference in the increase in neutralizing antibodies after vaccination between the CCP and control groups.CONCLUSIONThe trial demonstrated a trend toward better outcome in the CCP group without reaching statistical significance. A predefined subgroup analysis showed a significantly better outcome (long-term survival, time to discharge from ICU, and time to hospital discharge) among those who received a higher amount of neutralizing antibodies compared with the control group. A substantial long-term disease burden remains after severe COVID-19.Trial registrationEudraCT 2020-001310-38 and ClinicalTrials.gov NCT04433910.FundingBundesministerium für Gesundheit (German Federal Ministry of Health).

Donors for SARS-CoV-2 Convalescent Plasma for a Controlled Clinical Trial: Donor Characteristics, Content and Time Course of SARS-CoV-2 Neutralizing Antibodies.

BACKGROUND: Convalescent plasma is one of the treatment options for COVID-19 which is currently being investigated in many clinical trials. Understanding of donor and product characteristics is important for optimization of convalescent plasma. METHODS: Patients who had recovered from CO-VID-19 were recruited as donors for COVID-19 convalescent plasma (CCP) for a randomized clinical trial of CCP for treatment of severe COVID-19 (CAPSID Trial). Titers of neutralizing antibodies were measured by a plaque-reduction neutralization test (PRNT). Correlation of antibody titers with host factors and evolution of neutralizing antibody titers over time in repeat donors were analysed. RESULTS: A series of 144 donors (41% females, 59% males; median age 40 years) underwent 319 plasmapheresis procedures providing a median collection volume of 850 mL and a mean number of 2.7 therapeutic units per plasmapheresis. The majority of donors had a mild or moderate course of COVID-19. The titers of neutralizing antibodies varied greatly between CCP donors (from <1:20 to >1:640). Donor factors (gender, age, ABO type, body weight) did not correlate significantly with the titer of neutralizing antibodies. We observed a significant positive correlation of neutralization titers with the number of reported COVID-19 symptoms and with the time from SARS-CoV-2 diagnosis to plasmapheresis. Neutralizing antibody levels were stable or increased over time in 58% of repeat CCP donors. Mean titers of neutralizing antibodies of first donation and last donation of repeat CCP donors did not differ significantly (1:86 at first compared to 1:87 at the last donation). There was a significant correlation of neutralizing antibodies measured by PRNT and anti-SARS-CoV-2 IgG and IgA antibodies which were measured by ELISA. CCP donations with an anti-SARS-CoV-2 IgG antibody content above the 25th percentile were substantially enriched for CCP donations with higher neutralizing antibody levels. CONCLUSION: We demonstrate the feasibility of collection of a large number of CCP products under a harmonized protocol for a randomized clinical trial. Titers of neutralizing antibodies were stable or increased over time in a subgroup of repeat donors. A history of higher number of COVID-19 symptoms and higher levels of anti-SARS-CoV-2 IgG and IgA antibodies in immunoassays can preselect donations with higher neutralizing capacity.

Quality of irradiated and non-irradiated plateletpheresis concentrates stored in platelet additive solution.

INTRODUCTION: Platelet additive solutions (PAS) allow to maintain platelet storage properties in platelet concentrates (PCs). The aim of the present study was to evaluate the in-vitro quality of irradiated and non-irradiated PCs, suspended in PAS, over a storage period of 6 days. METHODS: Plateletpheresis donors fulfilling current eligibility criteria underwent plateletpheresis with the MCS+ blood cell separator. The PAS SSP+ was used to store platelets (PLT) for up to 6 days. Aliquots were drawn from the PCs after collection, at day 4, 5 and 6 of storage. A battery of tests was performed to analyse the quality of the PCs: PLT count, mean PLT volume (MPV), PLT activation marker CD 62, swirl, RBC and WBC contamination, pH, citrate, glucose, lactate and lactate dehydrogenase. RESULTS: An average of 2.53 ±â€¯0.21 × 1011 PLT were collected in a product volume of 231 ±â€¯5 mL in irradiated and 233 ±â€¯6 mL in non-irradiated PCs, respectively. RBC- and WBC-contamination were within the allowed ranges. Δ CD62 steadily decreased in irradiated and non-irradiated PCs while the pH was well maintained over storage time. Glucose and lactate levels of irradiated and non-irradiated PCs showed characteristic pattern of PC storage within acceptable ranges. CONCLUSION: Our data demonstrate that parameters of PC quality were well maintained over a storage period of 6 days using PAS. Irradiation had no impact on the quality of PCs. The product quality of irradiated and non-irradiated PCs met national and European guidelines.

Donor Safety in Haemapheresis: Development of an Internet-Based Registry for Comprehensive Assessment of Adverse Events from Healthy Donors.

BACKGROUND: Currently, there is an extensive but highly inconsistent body of literature regarding donor adverse events (AEs) in haemapheresis. As the reports diverge with respect to types and grading of AEs, apheresis procedures and machines, the range of haemapheresis-related AEs varies widely from about 0.03% to 6.6%. METHODS: The German Society for Transfusion Medicine and Immunohaematology (DGTI) formed a 'Haemapheresis Vigilance Working Party' (Arbeitsgemeinschaft Hämapheresevigilanz; AGHV) to create an on-line registry for comprehensive and comparable AE assessment with all available apheresis devices in all types of preparative haemapheresis: plasmapheresis (PLS), plateletpheresis (PLT), red blood cell apheresis, all kind of leukaphereses (autologous/allogeneic blood stem cell apheresis, granulocyte apheresis, lymphocyte/monocyte apheresis) and all possible types of multi-component apheresis. To ensure the comparability of the data, the AGHV adopted the 'Standard for Surveillance of Complications Related to Blood Donation' from the International Society for Blood Transfusion in cooperation with the International Haemovigilance Network (IHN) and the American Association of Blood Banks for AE acquisition and automated evaluation. The registry is embedded in a prospective observational multi-centre study with a study period of 7 years. RESULTS: A preliminary evaluation encompassed the time period from January, 2012 to December, 2015. During this time, the system proved to be safe and stable. Out of approximately 345,000 haemaphereses 16,477 AEs were reported (4.9%) from 20 participating centres. The majority of AEs occurred in PLSs (63%), followed by PLT (34.5%) and SC (2.2%). Blood access injuries (BAI) accounted for about 55% of the supplied AEs, whereas citrate toxicity symptoms, vasovagal reactions and technical events (e.g. disposable leakages, software failures) rather equally affected haemaphereses at 8-15%. Out of 12,348 finalized AEs, 8,759 (70.1%) were associated with a procedure-related break-off, with BAI being the prevailing cause (5,463/8,759; 62.4%). An automated centre- and procedure-specific AE evaluation according to the latest IHN standard and AGHV pre-settings is available within a few minutes. CONCLUSIONS: An on-line electronic platform for comprehensive assessment and centre-specific automated evaluation of AEs in haemaphereses has been developed and proved to be stable and safe over a period of 4 years.

Immunoglobulin G levels during collection of large volume plasma for fractionation.

BACKGROUND: There is a need of comprehensive work dealing with the quality of plasma for fractionation with respect to the IgG content as today most plasma derivates are used to treat patients with immunodeficiencies and autoimmune disorders. Therefore, a prospective study was carried out to analyse IgG levels before plasmapheresis and every 200ml collected plasma. MATERIALS AND METHODS: Fifty-four experienced plasmapheresis donors were recruited for subsequent 850ml plasmapheresis using the Aurora Plasmapheresis System. Donors peripheral blood counts were analysed before and after plasmapheresis using an electronic counter. Total protein, IgG and citrate were measured turbidometrically before, during and after apheresis as well as in the plasma product. Furthermore, platelets, red and white blood cells were analysed as parameters of product quality. RESULTS: An average of 2751±247ml blood was processed in 47±6min. The collected plasma volume was 850±1mL and citrate consumption was 177±15mL. A continuous drop of donors' IgG level was observed during plasmapheresis. The drop was 13% of the IgG baseline value at 800mL collected plasma. Total protein, IgG and cell counts of the plasma product met current guidelines of plasma for fractionation. CONCLUSION: Donors' IgG levels during apheresis showed a steady decrease without compromising the quality of plasma product.

Influence of lifting prescribing restrictions for losartan on subsequent sartan utilization patterns in Austria: implications for other countries.

INTRODUCTION: Prescribing restrictions for angiotensin receptor blockers (ARBs) limited their utilization in Austria. Recently, generic losartan became available with its prescribing restrictions lifted while still in place for patented ARBs. OBJECTIVES: The main aim of this study is to assess the impact of the lifting of the prescribing restriction on utilization of losartan in ambulatory care versus other single ARBs, expenditure per defined daily dose (DDD) of losartan as well as total ARB expenditure and utilization of ARB combinations. Finally, to suggest potential measures that could be introduced to further enhance ARB-prescribing efficiency. METHODOLOGY: A quasi-experimental study of the utilization of different ARBs alone or in fixed dose combinations using a segmented time series. Utilization measured in DDDs, defined as 'the average maintenance dose of a drug when used in its major indication in adults'. Costs measured as total expenditure for different ARBs as well as their expenditure/DDD. RESULTS: Losartan utilization increased significantly following the withdrawal of prescribing restrictions (p > 0.001). Utilization of single-sourced ARBs also increased , but the growth rate was appreciably reduced once restrictions were lifted for losartan (p > 0.01). As a result, total expenditure of single ARBs increased but at an appreciably lower rate than utilization, helped by total expenditure/DDD for losartan declining by 78% over the study period. There was continuing appreciable utilization of fixed-dose combinations. CONCLUSION: Lifting of prescribing restrictions for losartan significantly enhanced its utilization, increasing ARB-prescribing efficiency, providing direction to other European authorities. Additional reforms are being considered to further switch utilization away from single-sourced ARBs to additionally improve prescribing efficiency as more multiple sourced ARBs become available.

Potential to enhance the prescribing of generic drugs in patients with mental health problems in austria; implications for the future.

BACKGROUND: Scrutiny over pharmaceutical expenditure is increasing leading to multiple reforms. This includes Austria with measures to lower generic prices and enhance their utilization. However the situation for newer antidepressants and atypical antipsychotic medicines (AAPs) is different to PPIs, statins, and renin-angiotensin inhibitor drugs with greater tailoring of therapy and no wish to switch products in stable patients. Authorities welcome generics though given the high costs particularly of single-sourced AAPs. OBJECTIVE: Assess (a) changes in utilization of venlafaxine versus other newer antidepressants before and after availability of generics, (b) utilization of generic versus originator venlafaxine, (c) price reductions of venlafaxine over time and their influence on total expenditure, (d) utilization of risperidone versus other AAPs, (e) suggest potential additional reforms that could be introduced if pertinent to further enhance the use of generics. METHODOLOGY: A quasi-experimental study design with a segmented time series and an observational study. Utilization measured in defined daily doses (DDDs) and total expenditure per DDD and over time. RESULTS: No appreciable changes in the utilization of venlafaxine and risperidone after generics. The reduction in expenditure/DDD for venlafaxine decreased overall expenditure on newer antidepressants by 5% by the end of the study versus just before generics despite a 37% increase in utilization. Expenditure will further decrease if reduced prescribing of duloxetine. CONCLUSION: Depression, schizophrenia, and bipolar diseases are complex diseases. As a result, specific measures are needed to encourage the prescribing of generic risperidone and venlafaxine when multiple choices are appropriate. Authorities cannot rely on a "Hawthorne" effect between classes to enhance the use of generics. Measures may include prescribing restrictions for duloxetine. No specific measures planned for AAPs with more multiple-sourced AAPs becoming available.

Guideline-conformity of initiation with oral hypoglycemic treatment for patients with newly therapy-dependent type 2 diabetes mellitus in Austria.

PURPOSE: To determine guideline conformity of initiation of oral hypoglycemic (OH) treatment for type 2 diabetes in Austria; to study patient and prescriber correlates of recommended initiation with metformin monotherapy. METHODS: We used claims from 11 sickness funds that covered 7.5 million individuals, representing >90% of the Austrian population. First-time OH use was defined as a first filled prescription after one year without any OH drug or insulin. Among these incident users, we described the OH drug class used and defined correlates of initiation with metformin monotherapy. RESULTS: From 1/2007 to 6/2008, we identified 42,882 incident users of an OH drug: 70.8% used metformin, 24.7% used a sulfonylurea, and 4.5% initiated treatment with another class. We estimated the incidence of OH-dependent type 2 diabetes at 3.8-4.4 per 1000 patient-years. We conducted multivariate analyses among 39 077 patients with available prescriber information. Independent correlates of initiation with metformin were younger age, female gender, waived co-payment, more recent initiation, fewer hospital days and more therapeutic classes received in the year prior to first OH therapy (all p < 0.001). Prescriber specialty and age (p < 0.001), but not gender, were also associated with metformin initiation. Approximately 20% of metformin initiators had a second OH drug added within <18 months. While we were unable to ascertain specific contraindications to metformin (renal insufficiency, hepatic failure), <10% of the general population are expected to have these conditions. CONCLUSIONS: Seventy per cent of new initiators of OH treatment in Austria received metformin as recommended by international guidelines. At least 20% did not, taking into account possible contraindications, which provides an opportunity for intervention.

Comparing policies to enhance prescribing efficiency in Europe through increasing generic utilization: changes seen and global implications.

AIM: The aim of this article was to evaluate the influence of different demand-side measures to enhance the prescribing of generics in ambulatory care based on cross-national comparisons. METHODS: An observational retrospective study was conducted using administrative databases from across Europe, documenting changes in reimbursed utilization and expenditure of different proton pump inhibitors (PPIs) and statins between 2001 and 2007, alongside different reforms to enhance prescribing efficiency. Utilization was converted to defined daily doses (DDDs) and expenditures were converted to euros. Demand-side measures were collated under the '4 Es'--education, engineering, economics and enforcement--to enable comparisons on the nature and intensity of reforms between countries. RESULTS: There were considerable differences in the utilization of generics and patent-protected PPIs and statins among Western European countries. Decreased utilization of omeprazole and simvastatin, alongside increased utilization of esomeprazole, atorvastatin and rosuvastatin, was seen in countries with limited demand-side measures to counteract commercial pressures. Prescribing restrictions, or a combination of education, prescribing targets and financial incentives, had the greatest influence on enhancing the utilization of omeprazole and simvastatin. For example, there was a threefold reduction in the utilization of atorvastatin in Austria following prescribing restrictions. Multiple demand-side interventions generally had a greater influence than single interventions, with the impact appearing additive. Multiple interventions coupled with initiatives to lower prices of generics considerably enhanced prescribing efficiency. CONCLUSION: This cross-national study has demonstrated considerable variation in the utilization and expenditure of PPIs and statins across Europe, providing opportunities to further improve prescribing efficiency. The '4 Es' do provide an understandable methodology to document and compare the influence of different demand-side measures, with the influence varying by their extent and intensity. Further reforms are essential given current financial pressures. Consequently, further research will concentrate on the potential to develop a scoring system to help predict the possible impact of different demand-side measures on future utilization patterns.

Initiatives to enhance renin-angiotensin prescribing efficiency in Austria: impact and implications for other countries.

AIM: To assess the utilization of renin-angiotensin drugs, including combinations, in Austria in practice given the limited availability of diuretics, as well as the impact of recent reforms and initiatives on the utilization and expenditure of angiotensin-converting enzyme inhibitors (ACEis) and angiotensin receptor blockers (ARBs), following prescribing restrictions on ARBs immediately after their introduction. METHODS: Utilization of dispensed prescriptions in ambulatory care was captured from 2001 to 2007 using defined daily doses as well as defined daily doses/1000 inhabitants/day for patients covered by the social health-insurance system. The data were provided by the internal data warehouse of Hauptverband der Osterreichischen Sozialversicherungsträger. Total costs in Euros were used for the analysis to facilitate comparisons with earlier studies. RESULTS: There was appreciable utilization of fixed-dose diuretic combinations at between 36 and 38% of all renin-angiotensin products, in line with expectations. The reduction in expenditure/defined daily dose for originator and generic ACEis and their combinations is, again, in line with expectations, mirroring earlier findings for proton pump inhibitors and statins. ARB utilization was just under 27% of all renin-angiotensin products. This is higher than the low utilization rates seen with atorvastatin following its prescribing restrictions, and may reflect the difficulties if restrictions are based on subjective criteria. ARB utilization rates were lower or similar to other countries, who have implemented a different range of demand-side reforms to limit their prescribing with the advent of generic ACEis. CONCLUSION: The results confirm the successful implementation of the latest pricing policies and demand-side measures for generics and originators in Austria. We believe the prescribing restrictions for ARBs reduced their utilization in practice and offer an alternative approach to other demand-side measures.

Impact of reimbursement changes on statin use among patients with diabetes in Austria.

BACKGROUND: Statins have evolved as cornerstones of cardiovascular prevention in patients with diabetes. They are effective and can be cost-effective therapies, but increased use imposes a sizeable short-term burden on payors of health care. These have used various instruments to steer appropriate use of such treatment. It was the purpose of this study to examine the effect of two reimbursement policy changes of statin therapy in patients with diabetes in Austria. METHODS: Retrospective cohort study; time-series analysis. From Austrian sickness funds claims, we identified a closed cohort of 68,953 patients receiving treatment for diabetes in the first quarter of 2004. From April 2004 - December 2005, we ascertained use of statins for each monthly interval. Patients were censored at death. We used pseudo-experimental time-series regression to evaluate the effect of two policy changes on statin use and cost overall, as well as on the use of preferred versus non-preferred statins. RESULTS: Statin use among Austrian patients with diabetes increased from 20.6% to 24.9% during the time period. A policy change essentially expanding reimbursement for statins from secondary to primary prevention among patients with diabetes had no discernible effect on the observed trends in statin use. Another policy change that imposed random chart review for appropriateness of prescription of non-preferred statins including atorvastatin 10 mg yielded a marked drop in use of atorvastatin 10 mg and increase in the use of preferred statins, while leaving overall trends in statin use unaffected. CONCLUSIONS: Quantitative evaluation of new policies can provide important insights into the effectiveness und utility of such changes.

Policies to enhance prescribing efficiency in europe: findings and future implications.

INTRODUCTION: European countries need to learn from each other to address unsustainable increases in pharmaceutical expenditures. OBJECTIVE: To assess the influence of the many supply and demand-side initiatives introduced across Europe to enhance prescribing efficiency in ambulatory care. As a result provide future guidance to countries. METHODS: Cross national retrospective observational study of utilization (DDDs - defined daily doses) and expenditure (Euros and local currency) of proton pump inhibitors (PPIs) and statins among 19 European countries and regions principally from 2001 to 2007. Demand-side measures categorized under the "4Es" - education engineering, economics, and enforcement. RESULTS: Instigating supply side initiatives to lower the price of generics combined with demand-side measures to enhance their prescribing is important to maximize prescribing efficiency. Just addressing one component will limit potential efficiency gains. The influence of demand-side reforms appears additive, with multiple initiatives typically having a greater influence on increasing prescribing efficiency than single measures apart from potentially "enforcement." There are also appreciable differences in expenditure (€/1000 inhabitants/year) between countries. Countries that have not introduced multiple demand side measures to counteract commercial pressures to enhance the prescribing of generics have seen considerably higher expenditures than those that have instigated a range of measures. CONCLUSIONS: There are considerable opportunities for European countries to enhance their prescribing efficiency, with countries already learning from each other. The 4E methodology allows European countries to concisely capture the range of current demand-side measures and plan for the future knowing that initiatives can be additive to further enhance their prescribing efficiency.

Use of Generics-A Critical Cost Containment Measure for All Healthcare Professionals in Europe?

Pharmaceutical expenditures in ambulatory care rose rapidly in Europe in the 1990s and early 2000s. This was typically faster than other components of healthcare spending, leading to reforms to moderate future growth. A number of these centered on generic medicines with measures to lower reimbursed prices as well as enhance their prescribing and dispensing. The principal objective of this paper is to review additional measures that some European countries can adopt to further reduce reimbursed prices for generics. Secondly, potential approaches to address concerns with generics when they arise to maximize savings. Measures to enhance the prescribing of generics will also briefly be discussed. A narrative review of the extensive number of publications and associated references from the co-authors was conducted supplemented with known internal or web-based articles. In addition, health authority and health insurance databases, principally from 2001 to 2007, were analyzed to assess the impact of the various measures on price reductions for generic omeprazole and generic simvastatin vs. pre-patent loss prices, as well as overall efficiency in Proton Pump Inhibitor (PPI) and statin prescribing. The various initiatives generally resulted in considerable lowering of the prices of generics as well as specifically for generic omeprazole and generic simvastatin vs. pre-patent loss prices. At one stage in the UK, generic simvastatin was just 2% of the originator price. These measures also led to increased efficiency for PPI and statin prescribing with reimbursed expenditure for the PPIs and statins either falling or increasing at appreciably lower rates than increases in utilization. A number of strategies have also been introduced to address patient and physician concerns with generics to maximize savings. In conclusion, whilst recent reforms have been successful, European countries must continue learning from each other to fund increased volumes and new innovative drugs as resource pressures grow. Policies regarding generics and their subsequent impact on reimbursement and utilization of single sourced products will continue to play a key role to release valuable resources. However, there must continue to be strategies to address concerns with generics when they exist.

Impact of recent reforms in Austria on utilization and expenditure of PPIs and lipid-lowering drugs: implications for the future.

AIM: To assess the impact of a plethora of reforms and initiatives introduced in Austria since 2002 on the actual utilization and expenditure of proton pump inhibitors and statins. METHODS: Utilization of dispensed prescriptions in ambulatory care was captured from 2001 to 2007 using defined daily doses (DDD) as well as DDDs/1000 inhabitants/day for patients covered by the social health insurance system. The data were provided by the internal data warehouse of Hauptverband der Osterreichischen Sozialversicherungsträger. Total costs in Euros were used for the analysis from the payer's perspective. RESULTS: The reduction in the expenditure per DDD for both generic PPIs and statins was generally in line with expectations at over 60% of originator prices before multiple sources became available. There was also increased utilization of generics following the range of demand-side initiatives. This was 89.5% for generic omeprazole versus total omeprazole and 95.1% for generic simvastatin versus total simvastatin by the end of 2007. The utilization of atorvastatin fell substantially from 36.5% of all statins in 2002 to 10.7% by the end of 2007 following restrictions on its prescribing to patients not achieving target lipid levels with, for instance, generic simvastatin. The combined initiatives reduced expenditure per DDD for the PPIs and the statins by 41 and 60%, respectively, in 2007 versus 2001 levels. This reduction translated into lower expenditure for the statins in 2007 versus 2001 despite substantially increased utilization. CONCLUSION: The results provide examples to other European countries, especially the restrictions on atorvastatin utilization. Nevertheless, further initiatives will be needed to conserve resources as utilization rates grow in chronic disease areas. This includes potential lessons from other European countries.

Insight into recent reforms and initiatives in Austria: implications for key stakeholders.

Pharmaceutical expenditure continued to rise steadily in Austria during the 1990s and early 2000s despite a variety of reforms. However, recent reforms and initiatives have moderated the growth rate. These initiatives include transparent pricing of new drugs and generics, greater restrictions on the prescribing of new drugs and voluntary price reductions. Alongside this, there have also been initiatives to enhance rational and efficient prescribing. The lack of published data makes it difficult to fully analyze the impact of individual reforms. In addition, some reforms have only recently been introduced. Despite this, implications can be drawn for key stakeholder groups in the future. This includes pharmaceutical companies continuing to need to demonstrate substantially added benefit for their new drug to command average European prices. Otherwise, premiums will be restricted to a maximum 10% above the price of current standards. In addition, companies will need to continue to lower the price of their brands in interchangeable classes as standards become available as generics. The alternative will be prescribing restrictions. Further reforms will be needed in Austria to meet government growth targets for pharmaceutical expenditure of only 3-4% per annum, while continuing to fund new innovative drugs and increased volumes with greater prevalence of chronic diseases. Possible future measures and their implications for key stakeholder groups will also be discussed.

Assessment of complement activation during membrane-based plasmapheresis procedures.

Previous studies have suggested that plasmapheresis procedures using a separation membrane may activate the complement system and release anaphylatoxins. This study determines the content in C3a/C3a(des Arg) and C5a/C5a(des Arg) in plasma donations obtained by the new Haemonetics Filter Core (FC) procedure and compares it to Baxter Autopheresis C (Auto-C). FC performs sequential blood centrifugation and plasma filtration on a microporous polyethersulfone membrane, while Auto-C removes blood cells by simultaneous gravitation and filtration on a rotating nylon membrane. One group of 34 donors donated on FC and two groups of 30 and 10 donors on Auto-C. Plasma aliquots were taken from the plasma units within 30 min of the end of the collection procedures, frozen at < -30 degrees C and assessed for C3a and C5a at various time points of storage. Mean C3a/C3a(des Arg) in FC plasma (N = 34) was 1,151 (range: 526-2,991), 1,092 (range: 349-3498), and 507 (range: 307-815) ng/ml at time of collection and after 6 and 12 months of storage, respectively. Respective C5a/C5a(des Arg) was 26.6 (range 4.9-74), 18.9 (9.5-42.6), and 30.9 (range: 10.7-62.3) ng/ml. Mean C3a/C3a(des Arg) was higher in Auto-C (P < 0.001): 4,724 ng/ml (N = 10; range: 2,400-7 ,360) and > 4,149 ng/ml (N = 30; 2,408- > 6,430) after 3 and 18 months storage, respectively. Mean C5a/C5a(des Arg) was 32.1 ng/ml (N = 30; range: 10.6-57.2) after 18 months of storage. Complement activation in FC plasmas appears limited compared to Auto-C, suggesting better biocompatibility of this collection device and/or a favourable impact of the sequential cell centrifugation/filtration technology used. Further studies are needed to explain differences in complement activation between apheresis procedures and to assess clinical impacts, if any.

Residual cell content in plasma produced by three centrifugal apheresis procedures.

BACKGROUND: Understanding the impact of collection procedures on the residual amount of blood cells in plasma for transfusion and for fractionation is of current interest. This prospective work evaluated plasma donations collected on an apheresis machine (PCS 2, Haemonetics) with three different automatic centrifugal apheresis procedures, currently largely used in the US (Revision G) and in Europe (Revision F), and included a new procedure that uses a high-separation core (HSC) that is designed with a second separation chamber to further separate cells from plasma. STUDY DESIGN AND METHODS: A total of 90 collection procedures have been performed from a population of 37 donors, under comprehensively standardized conditions. There were 30 well-matched donors in each group. Plasma aliquots were taken from the plasma units within 30 minutes of the end of the collection procedures and immediately assessed for WBCs, RBCs, PLTs, and supernatant Hb. RESULTS: In Revision F and Revision G plasma donations, the mean numbers of WBCs were 83.1 x 10(4) and 311 x 10(4) per L; PLTs, 5.01 x 10(9) and 20 x 10(9) per L; and RBCs, 58 x 10(6) and 43 x 10(6) per L, respectively [corrected]. Significantly lower values were found with the HSC procedure (mean WBC, RBC, and PLT counts, 3.01 x 10(4)/L [p < 0.05], 9 x 10(6)/L [p < 0.001], and 3.5 x 10(9)/L [p < 0.001], respectively). The amount of free Hb was similar in all three procedures. CONCLUSION: Significant differences in numbers of cells in plasma were found depending on the centrifugal procedures used and the design of the separation bowl. The lowest level of cell contamination was found with the new HSC bowl, which without a filtration step, yielded plasma that met the standard for WBC-reduced plasma. Plasma collectors can select the most appropriate method of plasma collection based on donor criteria, use of plasma (transfusion, viral inactivation, or fractionation), and local or international regulations, when in place.

Protein composition and activation markers in plasma collected by three apheresis procedures.

BACKGROUND: Scientific and technical advances made in transfusion medicine sustain the need for more comprehensive understanding of the impact of collection procedures on the quality of plasma for fractionation and for transfusion. This prospective work evaluated protein composition and markers of activation in plasma donations collected with three different automatic collection procedures (performed on Haemonetics machines), including a new procedure using a high-separation core-molded bowl. STUDY DESIGN AND METHODS: A total of 90 collection procedures have been performed from a population of 37 donors, under comprehensively standardized conditions. Plasma aliquots were taken from the plasma units within 30 minutes of the end of the collection procedures and immediately frozen at -70 degrees C. Content in an extended range of proteins and of markers of activation of the coagulation and fibrinolytic systems has been measured using standard in vitro testing methods. RESULTS: Plasma donations had normal mean total protein, IgG, IgM, and fibrinogen content. The mean levels in coagulation FV, FVII, FVIII, and FXI and in antithrombin were above the standard international requirements. There was no sign of activation of the hemostasis system, as assessed by activated FVII, thrombin antithrombin complex, Prothrombin fragment 1+2, and D-dimers. Activated complement component C3 and C5 were low. CONCLUSION: Data indicates the good and consistent protein composition of plasma obtained by those automatic apheresis procedures. In particular, the new high-separation core procedure yields a high-quality plasma meeting requirements for transfusion and fractionation.