Citrate Reactions Research Articles

The influence of the frequency of donor plasmapheresis on the concentration of ions and proteins in the blood of donors

Introduction. Plasmapheresis is a routine procedure in many blood centers. The most common complications in plasma donors are vasovagal and citrate reactions. The effects of citrate exposure, repeated with different frequency over a long period of time, have not been sufficiently studied.Aim. to research the effect of the frequency of plasmapheresis on the concentration of ionic and protein composition in donor blood.Materials and methods. The concentration of protein in blood serum was measured using a biochemical method. The concentration of ions was carried out using an automatic blood electrolyte analyzer. Plasma donors were divided into groups depending on gender and frequency of plasmapheresis (1–5 times a year; 6–10 times a year; 11–26 times a year). The total number of donors involved in the study was 274 (155 men and 119 women).Results. A significant decrease in the concentration of bound calcium was revealed in the group of female donors who donated plasma 11–26 times compared to the group who donated plasma 1–5 times a year. A significant decrease in the concentration of iron ions was revealed in the group of female donors who donated plasma 11–26 times compared to the group who donated plasma 1–5 times a year. Statistically significant differences in the concentrations of total protein were revealed between all three groups of male donors, and between groups of female donors who donated plasma 1–5 times and 6–10 times a year; 1–5 times and 11–26 times a year.Conclusion. The use of data on changes in the parameters of ion and protein metabolism in donors of different sexes and different donation frequencies reduces the risk of developing a citrate reaction due to the selective selection of plasma donors.

ОЦЕНКА БЕЗОПАСНОСТИ И ЭФФЕКТИВНОСТИ МЕТОДИКИ МОБИЛИЗАЦИИ И СБОРА ГЕМОПОЭТИЧЕСКИХ СТВОЛОВЫХ КЛЕТОК У ДЕТЕЙ РАЗНЫХ ВОЗРАСТНЫХ ГРУПП СО ЗЛОКАЧЕСТВЕННЫМИ НОВООБРАЗОВАНИЯМИ: ОПЫТ ОДНОГО ЦЕНТРА

High dose chemotherapy (HDCT) with autologous hematopoietic stem cell transplantation (auto-HSCT) is used currently as a consolidating stage in cancer treatment protocols for children from different age groups with various malignant neoplasms. Auto-HSCT can improve both progression-free survival and overall survival of such patients. At the same time the optimization of the collection of autologous hematopoietic stem cells (HSCs) seems to be an important factor in the successful implementation of auto-HSCT. The purpose of this research was to evaluate the safety and effectiveness of the HSCs mobilization and collection method in children from different age groups with various malignancies. Materials and methods used: a single-center retrospective cohort study of 258 pediatric patients (median body weight 20.0 [13.8; 42.0] (7.0-95.0) kg and median height 116 [97; 155] (55.0-189) cm) with various cancers aged 1 to 18 y/o (median 78.0 [36; 144] (3-215) months old) who received treatment in Jan. 2020-Jan. 2023 at the Research Institute of Pediatric Oncology and Hematology named after Academician L.A. Durnov with the N.N. Blokhin Russian Cancer Research Center (Moscow, Russia). Patients were divided into 3 age groups: younger than 1 y/o, 1 to 10 y/o and 11 to 18 y/o. Results: 242 (93.8%) of HSC apheresis procedures were successful on the first attempt, 16 patients underwent repeated apheresis (a total of 274 procedures were performed). The median number of CD34+ cells obtained was 110.95 [45.6; 276.4] (0.70-2338.2) cells/µl, median apheresis duration was 253.5 [189; 338] (82-575) min. No serious complications were observed during the HSCs mobilization and collection in any patient. None of the patients developed hemodynamic disturbances. The main criteria for effectiveness was the CD34+/kg level, the median of which was 5.1 [2.4; 12.7] (0.01-95.6)•106. One of the safety criteria for the patients from all the three age groups was the absence of hemodynamic disorders and citrate reactions in the form of numbness, cyanosis of the skin and respiratory disorders. Another important safety criteria were the absence of a significant decrease in both platelet and hemoglobin levels. The median platelet levels prior to the procedure was 125.5 [68; 210] (14.0-815)•109/l and 129 [73; 210] (17.0-823)•109/l at the end of the procedure (p<0.001). Hemoglobin levels before and after the procedure were 100 [94; 110] (75-242) g/l and 99 [93; 109] (70-142) g/l, respectively (p<0.001). Considering it safe to reduce hemoglobin (g/l) and/or platelets (•109/l) by no more than 10 units in each measurement, in 87.6±4.1% (83.0-91.1) of observed cases the procedure was safe without statistically significant differences in all age groups. The effectiveness of the HSCs mobilization and collection method proposed by the Authors in children of the older age group (11 to 18 y/o) was the lowest and was statistically significantly different from the effectiveness in the group of children aged 1 to 10 y/o (p<0.001) with cancer and amounted to 84.5±4.4% (79.6-88.4). Conclusion: with the multidisciplinary team of practitioners, HSC apheresis in children is a safe and effective technique used as part of the complex cancer treatment in patients from poor prognosis groups. The apheresis algorithm that the Authors have proposed allows high-quality collection of CD34+ positive cells in amounts sufficient for further auto-HSCT.

A donor safety evidence literature review of the short- and long-term effects of plasmapheresis.

Many blood establishments are expanding plasmapheresis collection capacity to achieve increasing plasma for fractionation volume targets, driven by immunoglobulin product demand. Some adverse events occur in both apheresis and whole blood collection, such as venepuncture-related trauma and vasovagal reactions. Others are specifically related to the apheresis procedure, such as citrate reactions, haemolysis, infiltration and air embolism. Whilst plasmapheresis procedures are generally well tolerated, theoretical longer term donor health considerations, such as the effects on donor plasma protein levels, bone mineral density, iron deficiency and malignancy also require consideration. An evidence-based framework that supports a safe and sustainable increase in the collection of plasma is essential. Our review demonstrates a lack of high-quality evidence on risks and outcomes specifically in plasmapheresis. Whilst conservative procedural controls and donor harm minimization policies will mitigate risk, high-quality evidence is needed to facilitate practice change that is safe and sustainable and maximizes the potential of individual donor differences.

The determinants of donor safety and product quality in optimization of apheresis granulocyte harvest: An experience from a tertiary care oncology centre in India

Allogeneic granulocyte transfusions play a substantial role in treatment of lifethreatening neutropenia-associated infections in patients undergoing intensive chemotherapy and hematopoietic stem cell transplant. Granulocyte harvest by apheresis is considered a safe and effective method to obtain adequate therapeutic granulocyte dosage for clinical effectiveness. This study described the experiences associated with apheresis granulocyte harvest procedures in our tertiary care haemato-oncology centre. We have analysed the incidence of adverse events (AEs) with associated potential risk factors contributing to donor safety and improvement in product quality. Retrospective data of 131 healthy allogeneic donors who underwent granulocyte harvest from May 2016 to July 2020 were analyzed. AEs were observed in overall 29 procedures (22.13%), including 14.50% citrate reactions, 7.6% venous access-related reactions, and 1.52% vasovagal reactions. Older age (p = 0.012) and higher body mass index (p = 0.015) in donors were significant variables found associated with a higher incidence of AEs. There was no significant impact of AEs on granulocyte product yield (p = 0.41) with a median collection yield of 1.73 × 10 10 cells/ unit. In multivariate analysis, post-mobilization parameters like total leukocyte counts (p = 0.036), absolute neutrophil counts (p = 0.042), and platelet counts (p = 0.006) showed a positive correlation with higher product yield. All the donors successfully donated and tolerated granulocyte colony stimulating factor plus dexamethasone mobilization and granulocyte apheresis harvest without any serious AEs. Our study shows that optimal technical and procedural modifications during apheresis granulocyte harvest procedures can overcome the associated potential risks by providing donor safety and improving product quality.

Donor citrate reactions influence the phenotype of apheresis platelets following storage.

Platelet collection and processing methods, as well as donor attributes, can influence platelet function and quality during ex vivo storage. In this study, activation and procoagulant responses in platelets collected from donors experiencing a citrate reaction (CR) were investigated. Apheresis platelet components (n= 54) were stored in 100% autologous plasma and tested on days 1 and 5 post-collection. Platelet components were categorized into two groups according to whether the donor had experienced a CR during donation (n= 10; non-CR group, n= 44). Platelet aggregation was initiated with collagen and thrombin. Platelet phenotype was characterized by flow cytometry. Fibrinogen binding was assessed following collagen + thrombin stimulation (COATed platelets), and procoagulant activity was assessed using a procoagulant phospholipid assay (PPL). Platelet microparticle (PMP) subsets were enumerated by flow cytometry. Basal von Willebrand factor (VWF) binding was higher in the CR donations when compared with the non-CR group. Collagen aggregation was significantly higher in platelets from CR donations, in contrast to aggregation induced by thrombin. The proportion of phosphatidylserine (PS) positive PMP and PPL clotting time were higher in the CR group, in contrast to the number of basal PS+ platelets and COATed platelets following stimulation. Platelets donated by donors who experienced a CR during donation had higher platelet activation response and possibly a more procoagulant PMP phenotype, suggesting that this donor reaction might lead to increased platelet activation.

The new donor vigilance system in Denmark reveals regional differences in adverse reactions supposedly caused by variation in the registration.

In recent years, there has been an increased focus among blood bank professionals on the health and safety of blood donors. In 2019, the Danish Haemovigilance Committee designed a national donor vigilance system to improve the registration of adverse reactions (AR) in blood donors. The new donor vigilance system was implemented on 1 January 2020 and we here present the results from the first year of registration. AR categories, severity level and imputability score were defined based on the definitions from the International Society of Blood Transfusion, AABB and the European Commission directive 2005/61/EC, respectively. Across all severity levels, AR in Danish blood donors were found to be rare (1498 per 100,000 donations). Only 0.2% of the registered reactions were classified as serious (2.7 per 100,000 donations). Large regional differences were seen in the registration of citrate reactions and haematomas. Significant differences across regions in what to categorize as an AR were persistent even when including a severity score in the reporting. The Danish Haemovigilance Committee will commence a national work to align the definitions but suggests that this matter is raised to an international level as part of the current work to agree upon definitions for assessment of donor AR.

Adverse reactions to the Donation of Platelet by Apheresis and Related Factors in a Tertiary Level Care Blood Center

Background and Objectives: Although blood donation by apheresis is very safe, it is essential to identify the adverse reactions that happen and address the factors related to it so as to improve the donation experience both to the donors and the center accepting donations. This study was designed to assess the frequency of adverse reaction in donors undergoing apheresis for platelet donation and delineate the factors associated with the occurrence of such adverse donor reactions, if any. Methodology: This was an analytical retrospective study on the available data of all the donors who donated single-donor apheretic platelets in our blood center from January 2014 to October 2018. Results: The overall donor reaction rate was 8.3%, with the majority (4.7%) being a local reaction in the form of a hematoma. The other 3.6% were systemic reactions, among which 2.1% were citrate reactions and 1.5% vasovagal reactions (VVRs). The variables associated with a VVR were body weight <75 kg and diastolic blood pressure of <70 mmHg, whereas for citrate-related toxicities, it was the duration of the procedure and the amount of anticoagulant used. 4.7% of them were localized reactions in the form of the hematoma, which were more common in first-time donors. Conclusion: Adverse donor reactions to plateletpheresis are notable (8.3%) but generally mild. Auditing them to look for factors associated helps us review the policies and improve competencies among the staff to improve the safety of donors.

Adverse events associated with donor plateletpheresis: A 10-year experience from Vojvodina, Serbia

Background/Aim. Plateletpheresis (PLTP) is a medical procedure used for collecting donor platelets with multiple benefits for patients who will receive apheresis platelets. The procedure takes one hour and is well tolerated by donors. Nevertheless, adverse events (AEs) may occur during and after the PLTP procedure. The aim of the study was to determine the incidence and type of AEs associated with PLTP in donors. Methods. A retrospective analysis of AEs associated with donor PLTP was conducted at the Blood Transfusion Institute of Vojvodina from January 1, 2010, to December 31, 2019. Results. Out of 2,073 plate-let donors, 94.84% were multiple blood donors, predominantly male (98.55%). AEs were identified during 180 (8.68%) platelet donations with no statistical significance in occurrence in the first time donors (10.28%) and repeat donors (8.59%). Mild local reactions related to venous access (42.22%) were the most common AEs. Generalized symptoms were exhibited in 16.67% of donors, 26.11% exhibited symptoms related to apheresis (citrate reactions), and 15% exhibited those related to other complications. It was found that 95.55% of AEs occurred during PLTP and only 4.45% after it. Conclusion. Donor PLTP is a generally safe procedure, well tolerated by donors. Understanding risk factors for a possible occurrence of AEs provides support for adopting measures to prevent them.

MEDICAL AND ECONOMIC ANALYSIS OF THE CHOICE OF THERAPEUTIC PLASMAPHERESIS METHOD TO OPTIMIZE THE TRANSFUSION CARE QUALITY

The aim: To analyze the medical and economic aspects of the manual and different types of automatic plasmapheresis (manual, automatic centrifugal, automatic membrane, plasmapheresis with plasma therapy and mixed) used for therapeutic purposes. Materials and methods: The Baxter Auto-C, Haemonetics PCS2, Haemophenics, Baxter CPDA anticoagulant and saline, Baxter 16GA needles were used. Total protein was examined by the biuret method, hemoglobin by the Sally method, total bilirubin by the colorimetric photometric method, cell fragments by the Goryaev camera microscopy method; patient comfort – with a 10-point scale. Healthy blood donors participated in the study. Manual plasmapheresis was performed in 31 people, automatic plasmapheresis with centrifugal technology – 36 people, with membrane technology – 21 people, mixed technology – 36 people. Results: An analysis of the different technologies impact on hematological, psychological and medical and economic indicators was performed. Native hemoglobin was absent in the bloodstream and in the final plasma with all technologies. Bilirubin index was within normal limits. There were no cell fragments. It was proved the absence of significant differences in various technologies on hematological parameters. The lower level of patient comfort by manual plasmapheresis was established. Conclusion: All therapeutic plasmapheresis technologies have the same effect on the patient’s blood hematological parameters and did not have a negative impact on the body by the indicators: hemolysis, the presence of cell fragments, patient discomfort and citrate reactions during the standard procedure of sampling 800 ml of plasma. The most effective are plasmapheresis machines with centrifugal technology by medical and economic parametres.

Blood Donation-Related Adverse Reactions: Results of an Online Survey among Donors in Germany (2018)

Introduction: According to German legislation, reports of suspected serious adverse reactions (AR) associated with the donation of blood and its components are continuously being evaluated by the Paul-Ehrlich-Institut. This survey aimed at providing a more complete picture of the AR associated with the donation of blood and blood components. Materials and Methods: Eligible donors had the opportunity to anonymously report all AR occurring during or after their last donation by completing an online questionnaire. Reported AR were classified according to the Standard for Surveillance of Complications Related to Blood Donation. Donors’ self-assessment of AR seriousness was compared with the official severity classification as laid down by German legislation. Besides a descriptive statistical analysis, a multiple logistic analysis was performed to identify risk factors for AR. Results: A total of 8,138 data records were evaluated. Slightly more males (57.9%) participated in the survey and, except for donors aged ≥60 years, all age groups were equally represented. The majority of participants were whole blood donors (85.4%), repeat donors (97.2%), and stayed under observation in the blood establishment (BE) for more than 5 min (63.1%) after donation. Most participants did not report any reaction (72.5%), whereas 2,237 reported at least one AR (27.5%), 475 of whom underwent apheresis and 1,762 donated whole blood. Most AR occurred after leaving the BE (64.4%). Only a minority of participants required medical treatment (5.1%) or assessed the experienced AR as serious (3.9%). The most frequently reported donor AR were haematoma and other local reactions (57.6%). Vasovagal reactions without and with loss of consciousness were developed in 17 and 2% of the participants, respectively, whilst 7.6% experienced citrate reactions. New AR (i.e., allergic reactions and symptoms associated with iron deficiency) were reported as well. The occurrence of AR was linked to risk factors (i.e., female gender, young age, first-time donation, and thrombocytapheresis). Discussion: This survey yielded a more comprehensive AR spectrum, revealed a prolonged time to symptom onset, and identified risk factors for AR. This novel information could be implemented in an amended informed consent addressing common and rare AR.

Effect of citrate on ionized calcium levels during plateletpheresis procedures

Plateletpheresis procedures are generally well tolerated by most of the donors and adverse reactions due to citrate are generally mild and easily managed. The most common apheresis‐related reaction is hypocalcemia due to citrate anticoagulation which reduces ionized calcium and magnesium levels. The levels of ionized calcium levels decrease continuously from the baseline levels till end of the procedure and restore to baseline values post‐procedure. Symptoms of citrate toxicity are dependent on various factors like rate of citrate administration, duration of citrate infusion, dilution of citrate in extracellular fluid, redistribution, rate of citrate metabolism and the rate of citrate excretion. Citrate metabolism occurs in the liver, kidney, and skeletal muscle. Donors generally tolerate up to 20% decreases in ionized calcium levels. Citrate related reactions are generally transient and selflimiting. Citrate reactions can be differentiated into mild, moderate and severe. Management of citrate reactions includes mostly procedural modifications and/or oral calcium supplementation and rarely may require intravenous calcium supplementation. In donors with citrate related hypocalcemic symptoms, unresponsive to calcium supplementation, measurement of ionized magnesium should be considered as citrate decreased the ionized magnesium levels too. Management of such donors should be done with supplementation with magnesium sulfate. Management of donor reactions will make donors experience more pleasant, thereby increasing donor return rate and maintain the donor pool.

Risk of hypotensive reactions is increased when using partial saline replacement for therapeutic plasma exchange.

Partial normal saline replacement during plasma exchange procedures is a common practice to reduce procedure costs but may increase the risk of adverse events, such as hypotension and citrate reactions. The goal of this study was to compare adverse event rates for the patients that used albumin or albumin/saline as replacement. A retrospective chart review was done of plasma exchange procedures that used all albumin or 80% albumin to 20% normal saline (80/20) as replacement. The procedure type (all albumin vs 80/20), the percent of normal saline used, age, gender, and adverse events during the procedure were recorded. During the study period, 3624 procedures were documented for 401 patients (46% female), age range 0 to 93 years, of which 2453 (67.7%) used 80/20. Overall 91 procedures (2.5%) resulted in a hypotensive event, 26 (0.7%) of which were classified as moderate to severe hypotension, and 40 (1.1%) had reported citrate toxicity. After adjusting for age, gender, and diagnosis using a generalized linear mixed model and backward model selection, results showed that 100% albumin had a significantly lower risk of having hypotension than 80/20 (odds ratio (OR): 0.531 [0.298, 0.946], P = 0.032) and moderate to severe hypotension (odds ratio: 0.140 [95% confidence interval (CI): 0.031, 0.628], P = 0.010). Older age was also predictive of having hypotensive reactions (OR[95%CI] = 1.017,[1.0, 1.034], P = 0.047). Partial saline use as a replacement fluid with albumin during plasma exchange is associated with an increased risk of hypotension. Use of saline as replacement fluid during plasma exchange should be minimized especially in older patients.

Single-needle: an effective alternative to dual-needle peripheral access in therapeutic plasma exchange.

Apheresis treatments, which involve the removal of a component of blood, generally require one access and one return line to continuously draw and return blood into the extracorporeal circuit. At our center, we prefer to use peripheral venous access to avoid central line-related complications, especially infection. Motivated by patient-centered care, the single-needle (SN) option for therapeutic plasma exchange (TPE) offered on the Spectra Optia (Terumo BCT, Lakewood, CO) was evaluated. Five patients underwent procedures using both SN and dual-needle (DN) plasma exchange procedures using the Spectra Optia. TPE procedures ran a median of 51 (range:10-102) minutes longer using the SN-TPE option. Inlet flow rates, plasma removal efficiency, and incidence of citrate reactions were similar between SN- and DN-procedures. Patients reported great satisfaction with SN-TPE.

Reduction of body iron in HFE-related haemochromatosis and moderate iron overload (Mi-Iron): a multicentre, participant-blinded, randomised controlled trial

The iron overload disorder hereditary haemochromatosis is most commonly caused by HFE p.Cys282Tyr homozygosity. In the absence of results from any randomised trials, current evidence is insufficient to determine whether individuals with hereditary haemochromatosis and moderately elevated serum ferritin, should undergo iron reduction treatment. This trial aimed to establish whether serum ferritin normalisation in this population improved symptoms and surrogate biomarkers. This study was a multicentre, participant-blinded, randomised controlled trial done at three centres in Australia. We enrolled people who were homozygous for HFE p.Cys282Tyr, aged between 18 and 70 years, with moderately elevated serum ferritin, defined as 300-1000 μg/L, and raised transferrin saturation. Participants were randomly assigned, via a computer-generated random number, to undergo either iron reduction by erythrocytapheresis (treatment group) or sham treatment by plasmapheresis (control group). Randomisation was stratified by baseline serum ferritin (<600 μg/L or ≥600 μg/L), sex, and study site. Erythrocytapheresis and plasmapheresis were done every 3 weeks, the number of procedures and volume of red cells or plasma removed determined on the basis of each patient's haemoglobin, haematocrit, and serum ferritin concentration, as well their height and weight. In the erythrocytapheresis group, the target was to reduce serum ferritin to less than 300 μg/L. The number of procedures for the control group was based on the initial serum ferritin and prediction of decrease in serum ferritin of approximately 120 μg/L per treatment. The primary outcome was patient-reported Modified Fatigue Impact Scale (MFIS) score, measured at baseline and before unblinding. Analyses were by intention to treat, including the safety analysis. The trial is registered with ClinicalTrials.gov, number NCT01631708, and has been completed. Between Aug 15, 2012, and June 9, 2016, 104 participants were randomly assigned to the treatment (n=54) and control (n=50) groups, of whom 94 completed the study (50 in the treatment group and 44 in the control group). Improvement in MFIS score was greater in the treatment group than in the control group (mean difference -6·3, 95% CI -11·1 to -1·4, p=0·013). There was a significant difference in the cognitive subcomponent (-3·6, -5·9 to -1·3, p=0·0030), but not in the physical (-1·90 -4·5 to 0·63, p=0·14) and psychosocial (-0·54, -1·2 to 0·11, p=0·10) subcomponents. No serious adverse events occurred in either group. One participant in the control group had a vasovagal event and 17 participants (14 in the treatment group and three in the control group) had transient symptoms assessed as related to hypovolaemia. Mild citrate reactions were more common in the treatment group (32 events [25%] in 129 procedures) compared with the control group (one event [1%] in 93 procedures). To our knowledge, this study is the first to objectively assess the consequences of iron removal in individuals with hereditary haemochromatosis and moderately elevated serum ferritin. Our results suggest that serum ferritin normalisation by iron depletion could be of benefit for all individuals with hereditary haemochromatosis and elevated serum ferritin levels. National Health and Medical Research Council (Australia).

Safe and sustainable plasmapheresis

Background and ObjectivesOur aim is to present the recent Australian experience in trying to optimise collections from our apheresis program to meet the challenge of increasing demand for intravenous immunoglobulin. This is against a background of decreasing red cell demand, resulting in less recovered plasma from whole blood.Materials and MethodsWe extracted data from our donor and product databases and from targeted internal studies and audits. Data was analysed to determine the effects of donor factors, changes in collection processes and other interventions on the plasma volume, plasma quality, donor safety and donor return rates.ResultsVasovagal reactions remain a key adverse reaction in apheresis with implications not only for donor safety but also for donor return and therefore supply. Many factors influence reaction rates including donor selection and the details of the apheresis procedure. Other apheresis related complications include citrate reactions, iron deficiency and potentially bone health in long‐term donors. Changes in collection procedures can also affect product quality, which may negate benefits of increasing volume. Another key to maintaining supply is to optimise the frequency of donor visits, a major challenge in the non‐remunerated donor setting.ConclusionIn a time of increasing demand it is important to optimise immunoglobulin yield by retaining donors, increasing visit frequency and maximising volumes from each visit, whilst carefully balancing the risk of adverse reactions. Interventions must be assessed in terms of donor safety and also product yield. Both must be optimised if sustainability of plasma supply is to be achieved.

Characterization of the complications associated with plasma exchange for thrombotic thrombocytopaenic purpura and related thrombotic microangiopathic anaemias: a single institution experience

BackgroundPlasma exchange (PEX) is a life-saving therapeutic procedure in patients with thrombotic thrombocytopaenic purpura (TTP) and other thrombotic microangiopathic anaemias (TMAs). However, it may be associated with significant complications, exacerbating the morbidity and mortality in this patient group.Study Design and MethodsWe reviewed all PEX procedures over a 72-month period, following the exclusive introduction of solvent–detergent double viral-inactivated plasma in high-volume users, such as TTP, in the United Kingdom (UK). We documented allergic reactions to plasma, citrate reactions, complications relating to central venous access insertion and venous thrombotic events (VTE) in 155 patient episodes and >2000 PEX procedures.ResultsThe overall complication rate was low. Allergic plasma reactions occurred in 6·45% of the cohort with only one episode of acute anaphylaxis. Similarly, VTEs were 6·45%, not significantly greater than in medical patients receiving thromboprophylaxis, despite added potential risk factors in TTP. Citrate reactions were the most frequent complication documented, but toxicity was significantly reduced by administration of further calcium infusions during the PEX procedure. There were no serious central line infections and no catheter thrombosis.ConclusionOur data confirms that PEX continues to be a life-saving procedure in the acute TTP setting and, the procedure was not associated with an increased mortality and limited morbidity.

Safety of plasma exchange therapy in patients with myasthenia gravis

Plasma exchange (PLEX) is effective in myasthenia gravis (MG), but there are concerns about its safety. We collected data prospectively from 42 patients randomized to PLEX treatment in a comparison study with intravenous immunoglobulin (IVIg). Detailed information on the PLEX treatment methodology and adverse events are reported. Forty of 42 patients completed PLEX. Ninety percent were treated in an outpatient setting. Fifty-five percent had no complications, and 45% had mild-moderate reactions that did not require stopping treatment; the majority were citrate reactions and peripheral vascular issues that were easily treated. Fifty-seven percent of patients responded to treatment, and 83% completed PLEX via peripheral venous access. Two patients had severe adverse events: 1 related and 1 unrelated to PLEX. Comorbid disease and age did not predict reactions. PLEX is safe, effective, and well tolerated in patients with MG. Our results do not raise concerns about the safety of PLEX in patients with moderate-severe MG.

Donor vigilance: progress and challenges

Background Internationally, there is increased interest in reporting, treating and attempting to reduce complications of blood donation. Donor haemovigilance is the systematic monitoring of adverse reactions and incidents in the whole chain of blood donor care, with a view to improving quality and safety for blood donors.International Developments Several studies have described the risk factors for vasovagal reactions – female donors, young age, first‐time status, low body weight, etc. A water drink before donation, use of applied muscle tension and social support during donation have been found effective in reducing minor vasovagal reactions and/or increasing the likelihood of donors returning for subsequent donations. Haematomas and other venepuncture‐related complications are frequent and are the predominant cause of long‐term morbidity from complications of blood donation. International surveillance data on donor complications are captured in ‘ISTARE’ International Surveillance database for Transfusion‐associated Adverse Reactions and Events, which is being developed by the International Hemovigilance Network.Experience in The Netherlands: Better Monitoring of Donor Complications, Where Next? All donor complications and procedural problems are routinely recorded in the computer system eProgesa. Since 2009, the results have been monitored. An improved coding list was introduced in 2010 in order to record more details and cover new procedures such as Rhesus immunizations. The overall rate of donor complications increased from 0·64 in 2009 to 0·80 per 1000 whole blood collections (second half of 2010) and from 1·34 to 1·40 per 1000 plasmaphereses; there were no changes in donor demographics or procedures to explain this, so better recording is presumed. The recorded complications and procedural problems are regularly presented in team leaders’ and regional directors’ meetings. The data have been used to analyse the effect of a procedural modification: increasing the concentration of citrate solution used in plasmapheresis. The rate of terminating procedures because of citrate reactions was 0·14 per 1000 collections [95% confidence interval (CI) 0·018–0·27] before and 0·09 (95% CI 0·018–0·17) after the modification, signifying no relevant change. It is hoped that in 2012 a revised donor information brochure with instructions on avoiding vasovagal reactions will be piloted and subsequently tested. Nevertheless, only immediate and short‐term complications can be effectively addressed by the recording and analysis of complications. Longer term issues such as whole blood donor iron status are the subject of research in our country and abroad.Conclusion In our country as well as elsewhere, recording and monitoring the incidence of complications of blood donation has become the norm. Knowledge of risk factors and evidence‐based interventions will enable blood establishments worldwide to reduce donor complications. As yet, longer term complications are not well addressed.

Moderate and severe adverse events associated with apheresis donations: incidences and risk factors

The goal of this observational retrospective study was to evaluate various donor and procedural variables as potential risk factors for different types of moderate to severe adverse events (AEs) during apheresis collections. Data on all apheresis collections performed on Trima Accel (TA; CaridianBCT) instruments over a 28-month period were extracted from a donor database (Vista Information System, CaridianBCT) and reviewed along with AE reports from the same period. Donor and procedural variables were compared among uneventful procedures and those that resulted in various types of moderate to severe AEs, including presyncopal or syncopal (PS) episodes, citrate reactions (CR), reactions with both components (PS + CR), and self-reported incidents of significant venipuncture-related vascular injuries (VIs). A total of 59 moderate to severe AEs occurred among 15,763 procedures (0.37%), including 19 PS, 4 CR, 17 PS + CR, 12 VI, and 7 miscellaneous reactions. Greater blood loss and lower net fluid balance were associated with PS; female sex, older age, and smaller total blood volume (TBV) were associated with CR; and development of VI may be associated with female sex and smaller TBV. Younger age was not a risk factor for AEs. Apheresis collections performed by TA instruments are safe with a low incidence of significant AEs. Various types of AEs have different predisposing factors. Apheresis may be a safer option for donors with risk factors for PS reactions associated with whole blood collections, such as younger age, female sex, and small TBV.

Increased risk of citrate reactions in patients with multiple myeloma during peripheral blood stem cell leukapheresis

The citrate based anticoagulant ACD is commonly used in apheresis procedures. Due to its ability to decrease ionized calcium, citrate may cause unpleasant symptoms, such as paresthesias and muscle cramps, in patients undergoing therapeutic and donor apheresis. We noticed that patients with multiple myeloma (MM) undergoing autologous stem cell leukapheresis appeared to have more citrate reactions when compared to other patients undergoing the same procedure. A retrospective chart review was performed to evaluate 139 (of 151) consecutive patients with MM, amyloidosis, hematological and solid malignancies who had autologous peripheral blood stem cell collection between January 2007 and February 2008. Citrate reactions, ranging from mild (e.g., perioral tingling and parasthesias) to severe (e.g., nausea/vomiting and muscle cramps) were noted for 35 patients. Twenty-three of 63 patients with MM had documented citrate reactions, which was significantly higher than those with other hematological and solid malignancies (37% vs. 20%; P < 0.05, Relative Risk (RR) = 1.9). The severities of citrate reactions were the same in both groups; approximately 50% of patients in each group received i.v. calcium gluconate for treatment of hypocalcemia. No correlation between bisphosphonate therapy and citrate reactions were noted in our study group. Examination of available laboratory values related to calcium homeostasis, liver, and renal function failed to reveal a mechanism for the increase in citrate reactions observed. In summary, this single institution retrospective study indicates that patients with MM are more sensitive to citrate-induced hypocalcemia during leukapheresis when compared to patients with other hematological and solid malignancies. Strategies for decreasing citrate reactions (e.g., supplemental calcium and slowing return rates) should be considered for patient safety and comfort, especially in the MM population, on a prophylactic rather than reactive basis.