Analyses of registry data of patients with anti-GBM and antineutrophil cytoplasmatic antibody-associated (ANCA) vasculitis treated with or without therapeutic apheresis.

Therapeutic apheresis (TA) as a treatment for antibody-associated vasculitis (AAV) was questioned by the PEXIVAS although the MEPEX study favored TA. The aim of this study was to evaluate the efficacy of TA to improve renal function in patients consecutively included in the WAA-apheresis registry versus patients not treated with TA. MATERIALS AND METHODS: Included were 192 patients that suffered from anti-glomerular basement membrane disease (anti-GBM, n = 28) and antineutrophil cytoplasmic antibody-associated vasculitis of MPO or PR3 origin. Of these 119 had performed TA and the other 73 had not performed TA for theses diagnoses (CTRL). RESULTS: Elderly had an increased risk to die within 12 months (p = 0.002). All 28 anti-GBM had renal involvement, 21 dialysis dependent. At 3 month nine (36 %) did not need dialysis. Baseline data regarding renal function of AAV patients, subtype MPO and PR3, were worse in the TA groups than in CTRL. Recovery out of dialysis was better for the PR3-TA group compared with 1) the controls of MEPEX (RR 0.59, CI 0.43-0.80) and 2) the MPO-TA patients (RR 0.28, CI 0.12-0.68). The MPO-TA recovered similarly as the MEPEX-CTRL. Renal function improved most for TA-patients from baseline during the first 3 months (MPO-TA and PR3-TA) and stabilized thereafter and less for MPO-CTRL and PR3-CTRL. CONCLUSION: PR3-TA patients seem to have best chances to get out of dialysis. PR3-TA and MPO-TA improved residual renal function better than CTRL. The present study recommends reconsiderations to use TA for AAV especially those with PR3-vasculitis with severe renal vasculitis.

Taking therapeutic apheresis services to patients in South Africa: An eight year review of SANBS mobile therapeutic apheresis service, 2013-2020.

INTRODUCTION: A 20 year review of health and health care presents the multiple challenges faced by South Africans. Health and poverty is highlighted with 45% of population living on approximately US$ 2 per day and 10 million living on less than US$ 1 per day. Widening disparities in health care provision between public and private sector hospital services exist. The South African population includes the largest number of people living with HIV infection/AIDS of any country in the world, with a 70% estimate of 7.5 million people living with HIV on antiretroviral therapy. The South African National Blood Service provides a mixed model therapeutic apheresis service including mobile service and fixed-site therapeutic apheresis and an apheresis collection of hematopoietic stem cell (HPC-A) service. Therapeutic apheresis modalities offered by SANBS include plasmapheresis, red cell exchange, leukocyte and platelet reduction. In addition, collection of plasma, thrombocytes, mononuclear cells including CD34+ cells (HPCs) and granulocytes by apheresis for plasma and cellular therapies, and customised apheresis products for research purposes is offered. An operational database for the period 2013 to 2020 was reviewed to characterise the SANBS's mixed therapeutic apheresis service and HPC-A service from 2013 to 2020 in terms of patient numbers, patient demographics, patient procedures, therapeutic apheresis indication or diagnosis, therapeutic apheresis modality, hospital service type, and the American Society for Apheresis (ASFA) category of diagnosis. METHODS: A retrospective review of therapeutic apheresis patients referred to SANBS characterising patient numbers, patient demographics, patient procedures, therapeutic apheresis indication or diagnosis, therapeutic apheresis modality (Linz, 2017), hospital service type, and the ASFA category of diagnosis (Padmanabhan et al., 2019) for the period 01 January 2013 to 31 December 2020 was completed. Data is obtained from a SANBS operational routinely utilised to record patient procedure data. Patient procedure data is manually recorded by apheresis nurses and indexed on to the operational database, with both processes audited. The review period is a convenience sample. Storage of the database and access of the operational database is in compliance with the Protection of Personal Information Act (Government Gazette, 2013). Therapeutic apheresis modalities analysed include Plasmapheresis, Red Cell Exchange, Leukopheresis, Thrombocytapheresis, Lymphocyte collection, Granulocyte collection, Haematopoietic stem cell collection by apheresis and customised apheresis products for research purposes. Customised apheresis products for research purposes is excluded from this review. Descriptive statistics is used. RESULTS: For the review period, 2,485 unique patients with 120 unique indications as recorded by referring clinicians received 13,518 procedures involving 7 therapeutic apheresis modalities at 78 hospitals (21 public sector and 57 private sector) and at 3 SANBS blood donor centres in 7 provinces of South Africa. The age range of patients serviced is 4 months to 90 years (median = 39.5 years) (figure 1), 91% by procedure count was for patients 21 years of age or older, 62% were female, with 10,783 (79.6%) procedures performed in public sector hospitals. In all patients, the most common indications was plasmapheresis for thrombotic thromobocytopaenic purpura (52.5% of cumulative procedures), HPC-A for multiple myeloma (7.86%) and Antibody-mediated kidney transplant rejection (4.90%). Plasmapheresis was the most common therapeutic apheresis modality used (82.5% of cumulative procedures) followed by HPC-A (13.7%) and leukoreduction (3.39%). A range of indications for plasmapheresis (n = 65) and HPC-A (n = 41) were observed. Red cell exchange procedures was performed for patients with severe malaria and sickle cell disease indications. For leukoreduction indications, all patients were adults managed in public sector facilities and all were symptomatic. The most common indications were Chronic Myelogenous Leukemia, Chronic Lymphocytic Leukaemia and Multiple Myeloma. A pooled, total white cell count average of 457 × 109/L (range 141-689 × 109/L) prior to first procedure. Despite complex challenges for a national mixed model service, successful patient outcomes in emergent indications such as TTP (Louw et al., 2018; Swart et al., 2019) and engraftment post HPC-A in HSCT in multiple centres (Glatt, personal communication) are reported. CONCLUSION: The review confirms that apheresis medicine is increasingly used in South Africa in patients in both public and private sector, with the most common modalities being plasmapheresis, HPC-A and leukoreduction. Patients with HIV-associated TTP is the most commonly referred patient in both paediatric and adult patients and this is anticipated to continue. A growing HSCT transplant network capacity in South Africa is augmented through the mixed model mobile and fixed-site therapeutic apheresis services, including a mobile HPC-A service. The increasing number of HPC-A is a trend towards increasing numbers of patients support to HSCT for both adults and paediatric patients in private and public sector hospitals.

Analysis of extracorporeal photopheresis within the frame of the WAA register.

The aim of the study was to investigate safety and if extracorporeal photopheresis (ECP) may change health criteria (HC) and quality of life (QoL). MATERIAL AND METHOD: 560 patients (33 % women) were treated with ECP for a total of 13,871 procedures during a 17-years period. Mean age was 48 years (±18, range 3-81 years). Self-estimation of QoL was graded: 0 (suicidal) up to 10 (best ever) and HC: 0 (Bed ridden, ICU condition) up to 10 (athletic). Adverse events were analyzed. ANOVA and paired comparisons were performed. RESULTS: Patients were treated due to graft versus host disease (GVHD, n = 317), skin lymphoma (n = 70), solid organ transplants (n = 47), skin diseases (n = 20) and other diseases (n = 106). Adverse events (AEs) were registered in 5.4 % of the first treatments and in 1.2 % of the subsequent procedures. Severe AEs were present in 0.04 % of all procedures. No patient died due to the procedure. Tingling and stitching were the most common AE. For those with GVHD an improvement was noticed within approximately 10 procedures of ECP in the severity stage, QoL (from a mean of 6.1 to 6.8, p < 0.002) and the HC (6.1 -> 6.4, p < 0.014) and improved further with added procedures. CONCLUSION: Photopheresis is an established therapy with few side effects. The present study of soft variables indicate that GVHD shows benefits upon ECP within approximately 10 procedures in regard to the severity of mainly skin GVHD, and lower baseline levels of HC and QoL.

Evaluation of health and quality of life in apheresis patients - data from the WAA register.

OBJECTIVE: The World Apheresis Association (WAA) register contains data from more than 89 000 apheresis procedures in more than 12,000 patients. The aim of this study was to evaluate functional health and quality of life (QoL) in patients during apheresis treatment. MATERIAL AND METHODS: Estimates of health condition (HC) were made in 40,445 and of QoL in 22112 apheresis procedures. This study focused on a 10-step graded evaluation of HC (scale from: 'bedridden, unable to eat' to a level of 'athletic competition') and self-assessment of QoL (scale from: worst ever '0' to best ever '10'). Data were compared in relation to various apheresis procedures and if the patient underwent the first or subsequent apheresis procedure. RESULTS: Of the patients treated with plasma exchange (PEX) with centrifugation technique (n = 15787) 10% were 'bedridden, unable to come out of bed' while for patients treated with plasma filtration technique (n = 1018) the percentage was 27%. During the first procedure these figures were 16% and 30%, respectively. Self-estimates of QoL were graded 'zero' or '1' in 1.6% of patients during the first apheresis procedure; At the first contact patients undergoing PEX graded like this in 4.3%. CONCLUSION: Many of the patients undergoing apheresis treatment have poor HC and QoL at the start of therapy. Of all therapeutic apheresis procedures patients undergoing PEX had the lowest score of QoL.

Distribution of indications and procedures within the framework of centers participating in the WAA apheresis registry.

The WAA apheresis registry was established in 2003 and an increasing number of centers have since then included their experience and data of their procedures. The registry now contains data of more than 74,000 apheresis procedures in more than 10,000 patients. This report shows that the indications for apheresis procedures are changing towards more oncological diagnoses and stem cell collections from patients and donors and less therapeutic apheresis procedures. In centers that continue to register, the total extent of apheresis procedures and patients treated have expanded during the latest years.

Adverse events in apheresis: An update of the WAA registry data.

Apheresis with different procedures and devices are used for a variety of indications that may have different adverse events (AEs). The aim of this study was to clarify the extent and possible reasons of various side effects based on data from a multinational registry. The WAA-apheresis registry data focus on adverse events in a total of 50846 procedures in 7142 patients (42% women). AEs were graded as mild, moderate (need for medication), severe (interruption due to the AE) or death (due to AE). More AEs occurred during the first procedures versus subsequent (8.4 and 5.5%, respectively). AEs were mild in 2.4% (due to access 54%, device 7%, hypotension 15%, tingling 8%), moderate in 3% (tingling 58%, urticaria 15%, hypotension 10%, nausea 3%), and severe in 0.4% of procedures (syncope/hypotension 32%, urticaria 17%, chills/fever 8%, arrhythmia/asystole 4.5%, nausea/vomiting 4%). Hypotension was most common if albumin was used as the replacement fluid, and urticaria when plasma was used. Arrhythmia occurred to similar extents when using plasma or albumin as replacement. In 64% of procedures with bronchospasm, plasma was part of the replacement fluid used. Severe AEs are rare. Although most reactions are mild and moderate, several side effects may be critical for the patient. We present side effects in relation to the procedures and suggest that safety is increased by regular vital sign measurements, cardiac monitoring and by having emergency equipment nearby.

Bone density in apheresis donors and whole blood donors.

Apheresis donation using citrate causes acute decrease in serum calcium and increase in serum parathyroid hormone. Long-term consequences, such as decrease in bone mineral density (BMD), are not known. In this study, we compared the BMD of 20 postmenopausal apheresis donors (mean donation number 115 times in up to 15 years) with that of 20 whole blood donors (for 15 years or more) aged 55-70. BMD in the lumbar spine was not lower in apheresis donors than in blood donors (mean ± SD 1.00 ± 0.18 vs. 0.92 ± 0.12, P = 0.09). In the hip, BMD was not different between the groups.

Certification of donor apheresis nurses: keys to develop an effective training program.

Within Sanquin Blood Supply, a training program to train apheresis nurses was developed. The parts of the work for which qualification should be necessary was analysed. Based on this analysis, a modular program with theoretical and practical information and knowledge was developed. The modular program consists of two sections: a theoretical and technical / practical. The theoretical section consists of by the project group identified themes including basic hematology (e.g. the characteristics, kinetics, physiology and function of blood cells), basic apheresis physiology, indications for apheresis procedures, criteria for donors apheresis, difficulties and risks of procedures as well as the actions to be taken in case of side effects, and introduction to the apheresis machine available, including the mechanism of the machine. The program for the technical / practical section consists of machine and procedure knowledge (in theory and practise) and troubleshooting. To conclude each individual module, tests in theory and capability to perform procedures are taken. Each trainee needs to demonstrate to have sufficient insight and skill to master all the relevant critical features of the work. Also a text-book for the trainee was written. This educational program provides an approach to educate and test apheresis donor nurses. The combination of theoretical and practical components and monitoring of the progression are an important basis.

Allo-exposure status and leucocyte antibody positivity of blood donors show a similar relation with TRALI.

INTRODUCTION: The fraction of transfusion-related acute lung injury (TRALI) cases preventable by deferral of allo-exposed donors has previously been estimated, under the assumption this indirectly estimated the contribution of leucocyte antibodies to the occurrence of TRALI. Our aim was to estimate the fraction preventable by deferral of leucocyte antibody positive donors and to investigate the validity of allo-exposure as a marker for leucocyte antibodies. METHODS: All donors involved in a series of previously published TRALI patients were tested for leucocyte antibodies. The observed number of antibody positive donors was compared to the expected number. From this comparison we estimated the contribution of leucocyte antibodies to the occurrence of TRALI and compared this to the previously reported estimate for allo-exposed donors. RESULTS: Sixty-one TRALI patients were included. Of 288 involved donors 43 were expected and 67 were observed to be leucocyte antibody positive. The observed percentage of positive donors was 8.3% (95% confidence interval (CI): 5.1-11.5%) in excess of the expected. Overall 59% (95% CI: 34-85%) of TRALI cases was estimated to be preventable by the exclusion of all leucocyte antibody positive donors. For plasma-poor products this was 16% (95% CI: -5.0 to 36%). CONCLUSIONS: These estimates were similar to those previously published for allo-exposed donors. This suggests allo-exposure status can effectively be used in donor deferral strategies.

Prevalence of leucocyte antibodies in the Dutch donor population.

INTRODUCTION: Donor leucocyte antibodies have been associated with transfusion-related acute lung injury (TRALI) and can be present in allo-exposed donors. Donor deferral policies aiming at excluding allo-exposed donors are increasingly implemented worldwide. We aimed at assessing the prevalence of leucocyte antibodies in different subgroups of allo-exposed donors in the Dutch donor population. METHODS: Consecutive donors were enrolled during routine whole blood donation. Donors filled out a questionnaire on allo-exposure history. Blood samples were tested for human leucocyte antigens (HLA) (LifeScreen Deluxe and the Lifecodes LSA I/II assays) and granulocyte-reactive (GIFT, GAT, and MAIGA) antibodies. RESULTS: Six thousand and thirty-four consecutive donors (60% men) were included. A total of 2.5% reported a history of blood transfusions, and 51% (of female donors) reported a history of pregnancy. In never allo-exposed donors, the prevalence of granulocyte-reactive antibodies was 2.0% (95% CI: 1.6-2.4), and for HLA antibodies, it was 7.0% (95% CI: 6.3-7.8). In previously pregnant donors, the prevalence of granulocyte-reactive antibodies was increased to 3.0% (95% CI: 2.0-4.0), and for HLA antibodies, it was increased to 33% (95% CI: 30-36). Prevalence of leucocyte antibodies of all types depended on transfusion history, number of pregnancies, time since last pregnancy, and pregnancy outcome. CONCLUSIONS: Fourteen percent of Dutch blood donors are allo-immunized against HLA or granulocyte antigens. Deferral of all self-reported allo-exposed donors will decrease this prevalence to 9%. Deferral of all female donors and transfused male donors will result in a similar prevalence among remaining donors but approximately twice as many deferrals.

Granulocyte transfusions for pediatric patients and the establishment of national treatment guidelines and donor registry.

G-CSF/dexamethasone stimulated donor derived granulocyte transfusion (GTX) has been shown in non-randomized studies to be a useful co-therapy in immune-compromised patients unresponsive to conventional antimicrobial treatments. Reports of GTX are however usually single institution adult experiences. Substantiated pediatric data, other than in neonates, is less common.

Sick leave analysis among self-employed Dutch farmers.

BACKGROUND: Agriculture is one of the most physically demanding and risky industries. Aim The objective of this study was to provide baseline data on the diagnoses, occurrence and duration of sick leave of self-employed Dutch farmers. METHOD: A database of 22 807 sick leave claims of 12 627 farmers during the period 1994-2001 was analysed. RESULTS: Most of the claims (61%) were for musculo-skeletal injuries and disorders. The mean cumulative incidence (CI) was 10.2 claims per year per 100 farmers and did not change over time. However, it varied per agricultural sector and per age category, being lowest in arable farming and in the youngest age category and highest in mushroom farming and in the oldest age category. The duration of sick leave depended both on diagnosis and age category: the slowest recovery from sick leave was seen in farmers with respiratory diseases and farmers in the oldest age category. CONCLUSION: The results make it easier to identify groups of farmers to be targeted to prevent sick leave. To reduce the occurrence of sick leave in agriculture, the strategy should be to prevent musculo-skeletal injuries and disorders. Furthermore, a sector-specific approach is recommended, so that preventive actions can be focused on working conditions-specifically on workload and work safety. Efforts to shorten the duration of sick leave will also be valuable to obtain a reduction of sick leave.

Prevalence of and risk factors for HIV infection in blood donors and various population subgroups in Ethiopia.

The aim was to determine the prevalence of HIV infection and risk factors for HIV infection in various population subgroups in Ethiopia. Serum panels from blood donors (n = 2610), from various population subgroups in Ethiopia were tested for anti-HIV-1/2 by ELISA. All ELISA repeatedly reactive samples were subjected for confirmation by immunoblot (IB) and anti-HIV-1 and anti-HIV-2 specific ELISAs. 155/2610 (5.9%) blood donors were HIV-1 infected. Of pregnant women, 84/797 (10.5%) were HIV-1 infected, and 1/797 (0.1%) was HIV-2 infected. 1/240 (0.4%) individuals from the rural population were HIV-1 infected. 198/480 (41.3%) female attendees, and 106/419 (25.3%) male attendees at sexual transmitted disease (STD) clinics were HIV-1 infected. One (0.2%) male, and 2 (0.4%) female STD patients were infected with both HIV-1 and HIV-2. It was concluded that the prevalence of HIV-1 infection varied from 0.4% among urban residents to 25.3-41.3% among STD attendees. There is a low prevalence of HIV-2 present in Ethiopian subjects. Risky sexual behaviour is significantly associated with HIV-infection in Ethiopia.