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Objectives To establish, in an unselected population of London haemoglobinopathy patients, transfusion requirements, blood antigens/alloantibodies, transfusion modalities, burden of transfusion reactions and donor exposure. Background Haemoglobinopathy patients are among the most highly transfused patient populations, and the overall population and number of patients on long-term transfusion programmes are increasing. To provide a safe and efficacious transfusion service for patients, it is important to understand current practice, morbidity associated with transfusion, efficacy of different transfusion modalities and geno-/phenotype requirements. Methods Data on 4451 transfusion episodes in 760 patients from 12 London hospitals were collected retrospectively over a 6-month period in 2011. Results Alloimmunisation prevalence was 17% for sickle cell disease (SCD) and 22% for thalassaemia, most commonly anti-Rh/Kell/Kpa /Cw . Rh phenotypes differed between SCD (Ro r 59.8%/R1 r 15.9%/R2 r 15.6%) and thalassaemia (R1 R1 29.6%/R1 r 28.4%/R1 R2 15.4%). Recording of pheno-/genotypes fell below recommendations. A 2-weekly manual exchange and 3-weekly automated exchange came closest to achieving presumptive targets. In adults with thalassaemia, the mean blood requirement was 36 units per year; for SCD, erythrocytapheresis was carried out every 7 weeks with 66 units; for manual exchange, it was 38 units every 4 weeks; and for simple transfusion, it was 30 units p.a. every 4 weeks. Conclusion Transfusion modality choice was influenced by the resources available-children mostly received simple transfusions, and adults received erythrocytapheresis; the relationships between frequency of exchanges/transfusion modality/target HbA% were not simple, possibly reflecting the difference in recipient erythropoiesis and consequent transfusion modality selection bias; adherence to existing and current guidelines regarding geno-/phenotyping was limited; and alloimmunisation had a low incidence and high prevalence in both disorders.

The American Society for Apheresis (ASFA) Journal of Clinical Apheresis (JCA) Special Issue Writing Committee is charged with reviewing, updating, and categorizing indications for the evidence-based use of therapeutic apheresis in human disease. Since the 2007 JCA Special Issue (Fourth Edition), the Committee has incorporated systematic review and evidence-based approaches in the grading and categorization of apheresis indications. This Seventh Edition of the JCA Special Issue continues to maintain this methodology and rigor to make recommendations on the use of apheresis in a wide variety of diseases/conditions. The JCA Seventh Edition, like its predecessor, has consistently applied the category and grading system definitions in the fact sheets. The general layout and concept of a fact sheet that was used since the fourth edition has largely been maintained in this edition. Each fact sheet succinctly summarizes the evidence for the use of therapeutic apheresis in a specific disease entity. The Seventh Edition discusses 87 fact sheets (14 new fact sheets since the Sixth Edition) for therapeutic apheresis diseases and medical conditions, with 179 indications, which are separately graded and categorized within the listed fact sheets. Several diseases that are Category IV which have been described in detail in previous editions and do not have significant new evidence since the last publication are summarized in a separate table. The Seventh Edition of the JCA Special Issue serves as a key resource that guides the utilization of therapeutic apheresis in the treatment of human disease. J. Clin. Apheresis 31:149-162, 2016. © 2016 Wiley Periodicals, Inc.

Erythrocytapheresis, red blood cell (RBC) depletion, and RBC exchange transfusions are apheresis techniques used to rapidly lower the circulating RBC mass or to exchange the patient erythrocyte mass with donor RBC. Automated RBC exchange is performed using an apheresis device, while manual RBC exchange is based on sequential phlebotomies and isovolemic replacement. Compared to simple RBC transfusions, RBC exchange offers several advantages, e.g., a lower risk for iron accumulation and efficient control of pathological erythrocyte populations. Disadvantages are the higher costs of the procedure, the increased use of donor RBC, and the requirement of apheresis devices and trained hospital staff. The most frequent indication for RBC exchange is sickle cell disease (SCD). RBC exchange transfusions are standard treatment in SCD patients with a history of or a risk for acute stroke and are clinical options for other acute complications of SCD. The most common indication for RBC depletion is the removal of donor RBC from the bone marrow grafts in major ABO-incompatible allogeneic hematopoietic stem cell transplantation to avoid immediate hemolysis. Rare indications for RBC exchange are severe infections with intraerythrocytic pathogens such as malaria or babesiosis and severe erythrocytosis or hereditary hemochromatosis where the aim is to rapidly decrease RBC populations or the iron content. However, only few high-quality studies are available looking at the efficacy of RBC exchange in the different disease entities, and treatment is often based on low levels of evidence and should therefore be decided in close collaboration with a transfusion medicine specialist.

INTRODUCTION Indications for apheresis procedures are expanding; however, the evidence for many is low quality. A better understanding of apheresis patterns in the United States is needed to better plan prospective research studies. METHODS Data from January 1, 2013, to September 30, 2015, were analyzed from the IBM MarketScan Research Databases of de-identified health insurance claims data of several million enrollees at all levels of care from large employers and health plans across the United States. Apheresis procedures were identified by International Classification of Diseases, Ninth version (ICD-9) and Current Procedure Terminology (CPT) codes. RESULTS Combining inpatients and outpatients, 18 706 patients underwent 70 247 procedures. The patients were 52.7% female, 5.1%

Contains fulltext : 234969.pdf (Publisher’s version ) (Open Access) BACKGROUND AND AIMS: Standard treatment for naïve hereditary hemochromatosis patients consists of phlebotomy or a personalized erythrocytapheresis. Erythrocytapheresis is more efficient, but infrequently used because of perceived costs and specialized equipment being needed. The main aim of our study was to develop a model that predicts the number of initial treatment procedures for both treatment methods. This information may help the clinician to select the optimal treatment modality for the individual patient. METHODS: We analyzed retrospective data of 125 newly diagnosed patients (C282Y homozygous), treated either with phlebotomy (n = 54) or erythrocytapheresis (n = 71) until serum ferritin (SF) reached levels ≤100 μg/L. To estimate the required number of treatment procedures multiple linear regression analysis was used for each treatment method separately. RESULTS: The linear regression model with the best predictive quality (R(2) = 0.74 and 0.73 for erythrocytapheresis and phlebotomy respectively) included initial SF, initial hemoglobin (Hb) level, age, and BMI, where initial SF was independently related to the total number of treatment procedures for both treatment methods. The prediction error expressed in RMSPE and RMSDR was lower for erythrocytapheresis than for phlebotomy (3.8 and 4.1 vs 7.0 and 8.0 respectively), CONCLUSIONS: Although the prediction error of the developed model was relatively large, the model may help the clinician to choose the most optimal treatment method for an individual patient. Generally erythrocytapheresis halves the number of treatment procedures for all patients, where the largest reduction (between 55% and 64%) is reached in patients with an initial Hb level ≥ 9 mmol/L (14.5 g/dL). ClinicalTrials.gov number NCT00202436.

The aim of our study was to assess the efficacy of red blood cell exchange (RBCx) using a Spectra Optia® automated apheresis system in children with sickle cell disease (SCD). We used automated RBCx to treat acute and chronic complications in 75 children with SCD who had a median age of 10 years [7–13]. We analyzed 649 RBCx sessions. Peripheral venous access was limited in a number of the children, and thus a femoral double-lumen central venous catheter was required. We recommend heparin locking with 500 units in each lumen of the catheter. To prevent complications, we ensured that all patients had achieved a post-RCE HbS level of

Red cell transfusion remains a critical component of care for acute and chronic complications of sickle cell disease. Randomized clinical trials demonstrated the benefits of transfusion therapy for prevention of primary and secondary strokes and postoperative acute chest syndrome. Transfusion for splenic sequestration, acute chest syndrome, and acute stroke are guided by expert consensus recommendations. Despite overall improvements in blood inventory safety, adverse effects of transfusion are prevalent among patients with sickle cell disease and include alloimmunization, acute and delayed hemolytic transfusion reactions, and iron overload. Judicious use of red cell transfusions, optimization of red cell antigen matching, and the use of erythrocytapheresis and iron chelation can minimize adverse effects. Early recognition and management of hemolytic transfusion reactions can avert poor clinical outcomes. In this review, we discuss transfusion methods, indications, and complications in sickle cell disease with an emphasis on alloimmunization.

Polycythaemia vera is one of several classical myeloproliferative neoplasms that may occur in a juvenile onset or late-onset adult forms. It is linked to specific genetic mutations that cause a deleterious elevation in the patient's red cell mass. The discourse on genetics includes an expose on the molecular biology of the disease and how a shared JAK2 V617F mutation can co-exist among three distinct neoplasms. Concepts of genetics and immunology help define the origin and behaviour of the disease: the tracking of allele burdens of mutations (genetic dosage), the timing or order of acquired mutations, the import of bystander mutations and the onco-inflammatory response; all theories are invoked to explain the progression of disease severity and potential transformational leukaemia. The World Health Organization's diagnostic criteria are accessed to focus on the subtleties of the Hb laboratories and sifting through the challenging listing of differential diagnoses that mimic PV, and our report includes an overview of manual and automated phlebotomy (erythrocytapheresis) procedures, enumerating their clinical indications, significance of temporary phlebotomy resistance and optimizing safety/ efficacy, quality and cost. Stratification of low and high-risk disease distinguishes when to commence chemo-cytoreductive therapy in the high-risk patient to prevent thrombotic complications. Drug resistance is circumvented by artfully switching drugs or using novel drug designs.

BACKGROUND Chronic transfusion in sickle cell disease (SCD) remains the gold standard therapy for stroke prevention and for patients with severe disease despite adequate hydroxyurea treatment. The aim of our study was to assess the safety and efficacy of automated red blood cell exchange (aRBX) in patients with SCD previously treated with manual exchange transfusion (MET). Costs related to transfusion and chelation overtime were evaluated. STUDY DESIGN AND METHODS Beginning in January 2012, children with SCD who weighed 30 kg or more on MET could switch to aRBX. Clinical, biological, and procedures' data, including costs, were recorded for the last 6 months on MET and compared to those after the first and the second year on aRBX. RESULTS Ten patients switched from MET to aRBX at a median age of 11.8 years. After the switch, median hemoglobin S (HbS) increased significantly (33.5% on MET compared to 45% on aRBX; p

Background: Erythrocytapheresis, or red blood cell exchange (RCE) is a non-invasive procedure in which a patient's erythrocytes are removed from the bloodstream while being replaced with erythrocytes from blood donors. RCE is commonly used as a transfusion technique in patients with sickle cell disease (SCD) to help treat and prevent complications associated with sickling of erythrocytes and iron overload. The AABB consensus report (1) outlines the procedural guidelines for RCE including appropriate indications and ideal forms of vascular access. However, the guidelines make no recommendation for determining the hematocrit (Hct) of the red cell bags for the procedure. Institutions take several different approaches to determine how many red cell units to exchange. The number of units needed depends on the volume and Hct of the individual units as well as the patient's pre-procedure Hct and HbS levels, height, weight, and the desired HbS and Hct targets. Red cell units are routinely labeled with volume, but are not generally labeled with Hct. The AABB consensus report (1) states that some institutions use an estimated Hct of 56% to 57% for each unit. The report rationalizes the use of an estimated Hct for input for the RCE, by citing the approximated Hct of bags of red cells (55% to 60%) with additive solution produced from whole blood donation, based on limited data. The goal of our study was to determine the average Hct on the red cell units used for RCE. Methods: This study used a retrospective chart review to investigate the Hct of red cell units during a RCE in a calendar year. Our institution uses pre-storage leuko-reduced red blood cells units in citrate phosphate dextrose adenine (CPDA-1) and adsol preservative (AS-1), which are 21 days old or less for RCE. The average Hct of the bags of red cells infused during the procedure was determined by accessing each bag for a small sample of blood to determine the Hct. Data was excluded if the patient did not meet standard weight requirements (> 30 kg) or required additional treatment protocols including the use of washed cells or machine priming. Results: A total of 297 encounters were recorded for 30 different patients. A total of 1953 bags (approximately 517 liters of red cell units in volume) were administered. Data from the encounters were used to calculate measures of central tendency. The average calculated Hct for each encounter was 63.3%, with a median and mode Hct being 63% and 62%. The range of Hct from the bags was 54.6% to 72.9%. The average Hct of the bags ranged from 60.6% (in March) to 64.8 % (in July). Conclusions: Our study suggests a higher average Hct of transfused red cell units than stated in the AABB consensus report (1), which was based on limited data. Our findings indicate that a standardized average of 63.3%, would be appropriate for our institution. Conversely, our findings also signify that the standardized average Hct must be determined in each institution prior to their application for RCE. However, our data also reveals that it is possible to subject patients to estimates as far as 9.7% above and 9.6 % below the true average Hct of the red cell bags used. The process of determination of Hct for each of the red cell units increases the time of pre-service activities, laboratory costs, and the overall infusion center time for the patients leading to higher costs per infusion. Consequently, using a standardized average of the Hct would result in cost savings. We have therefore adopted the practice of using the standardized average of Hct of 63.3% for RCE in our patients. Reference: 1. Biller E, Zhao Y, Berg M, Boggio L, Capocelli KE, Fang DC, Koepsell S, Music-Aplenc L, Pham HP, Treml A, Weiss J, Wool G, Baron BW. Red blood cell exchange in patients with sickle cell disease-indications and management: a review and consensus report by the therapeutic apheresis subsection of the AABB. 2018 Aug;58(8):1965-1972. doi: 10.1111/trf.14806 Disclosures Munson: Terumo Medical Corporation: Consultancy, Honoraria, Speakers Bureau. Raj: Terumo Medical Corporation: Honoraria, Speakers Bureau; Global biotherapeutics: Speakers Bureau; Forma therapeutics: Consultancy.

Background: Erythrocytapheresis or red cell exchange (RCE) is an invaluable treatment option for patients with complications related sickle cell disease, including acute stroke, stroke prevention, acute chest syndrome, and recurrent pain crisis. The procedure entails the removal of each patient's red blood cells containing the abnormal sickle hemoglobin and replacing them with normal red blood cells carrying non-sickled hemoglobin. Adequate vascular access is essential for erythrocytapheresis to allow for high flow rates and various forms of access are used including peripheral veins and central venous access devices. Our center typically uses a single vortex port (Angiodynamics, Walnut Creek, CA) with placement of a peripheral IV at time of procedure in order to maintain a circuit for exchange. Using peripheral access reliably becomes particularly difficult in young patients and those that require multiple access over time due to scaring. To ensure a successful procedure in patients with poor peripheral access, a single-needle (SN) option for TPE (SN-TPE) that is available on Spectra Optia (Terumo BCT, Lakewood, CO) was used. The single-needle procedure utilizes intermittent, rather than continuous, flow, and thus requires extra procedure run time. One discontinuous cycle consists of "exchanging red cells," which is the drawing of blood and removal of the red cells, and "adjusting the volume in the reservoir," which is the returning of blood. These cycles continue until the procedure is complete. This procedure allows us to continue RCE in a select number of patients with poor vascular access. Methods: We evaluated our institutional experience on patients treated using single-needle RCE. In addition, information regarding each RCE session was collected including duration of procedure and inlet flow rate. Results: An average of 45 RCE procedures are performed each month. Patients are scheduled every 3 to 8 weeks, with an average of every 4-5 week frequency. We started the Single Needle option in July of 2019 on 3 patients: one adult aged patient and 2 pediatric patients. By the end of 2019 we had perform a total of 27 SN procedures. In 2020, we performed a total of 112 SN procedures, average of 9 procedures each month. As of the first 6 months of 2021, we have completed 35 SN procedures, averages 6 a month. In patients undergoing single needle exchange we were able to increase inlet flow rates from an average of 30-50ml/min to 60-80ml/min. This decreased the duration of run times from 120-198 min to 77- 119 min. Pre and post hemoglobin S% was comparable between dual and single exchange patients and there was no change in the interval between RCE sessions. Conclusion: With our increasing experience with single-needle RCE, our findings suggest that RCE can be successfully completed using the single-needle option with no impact on pre- and post-exchange hemoglobin S% levels. There was a reduction in the total length of procedure due to ability to maintain higher inlet rates and decreased time to obtain access for RCE. The single needle option also improved patient satisfaction due to more reliable access and negating need for peripheral IV access. Disclosures Munson: Terumo Medical Corporation: Consultancy, Honoraria, Speakers Bureau. Raj: Forma therapeutics: Consultancy; Terumo Medical Corporation: Honoraria, Speakers Bureau; Global biotherapeutics: Speakers Bureau.

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).

Erythrocytapheresis is an important procedure in the management of certain complications of sickle cell disease, including acute stroke, stroke prevention, acute chest syndrome, and multiorgan failure. Erythrocytapheresis in sickle cell disease simply entails the removal of the patient's red blood cells containing the abnormal sickle hemoglobin and replacing them with normal red blood cells carrying normal hemoglobin. In these procedures, the patient's plasma is not exchanged but is returned to the patient. Several studies have demonstrated that the plasma of patients with sickle cell disease contains several components that increase blood viscosity and initiate or promote vaso-occlusion. These factors include increased levels of globulins, especially immunoglobulin G, acute-phase reactants, fibrinogen, coagulation factors, inflammatory mediators, and heme in the steady state and increase further during painful crises. This may explain why, in certain complications of sickle cell disease, such as acute chest syndrome, hepatic crisis, and priapism, erythrocytapheresis by itself may not be effective despite repetitive cycles of red blood cell exchange. The use of therapeutic plasma exchange in addition to erythrocytapheresis in these situations seems to be useful in resolving them more efficiently. The role of therapeutic plasma exchange in the management of certain complications of sickle cell disease needs further evaluation. This commentary addresses the role of therapeutic plasma exchange in the management of complications of sickle cell disease.

Sickle cell-beta thalassemia is a double heterozygous state. Red cell exchange (RCE) transfusion reduces the concentration of sickle cells without increasing the hematocrit or whole-blood viscosity. It can be performed manually or by erythrocytapheresis. RCE transfusion is an effective tool for both acute and chronic complications of sickle cell disease. In patients unaffording erythrocytapheresis, even manual RCE can give favorable results. A 37-year-old male, a known case of sickle cell-beta+ thalassemia (βsβ+), presented with avascular necrosis of right femur and humeral head. He was posted for the right hip arthroplasty and shoulder hemiarthroplasty. Successful manual RCE transfusions were done. The hemoglobin S levels decreased postmanual RCE procedures, and the patient was operated successfully.

Background The aim of this study was to determine retrospectively the efficacy of combined therapy using erythropoietin (EPO) and erythrocytapheresis (EA) in patients with hereditary hemochromatosis (HH) who did not tolerate phlebotomy. Patients and Methods Twenty patients (age range, 43–74 years) with genetically confirmed HH had received low-dose EPO (4,000 IU) in accordance to the patient's hemoglobin levels between each EA session. Laboratory parameters including hemoglobin, ferritin, transferrin, and iron were measured at regular intervals. Results Anemia did not occur in a single patient and no serious side effects were observed. Combined treatment with EPO and EA was well tolerated, and all 18 patients who suffered from fatigue prior to therapy recovered. Median ferritin values were 678.5 ng/L before treatment and 145 ng/L after treatment. Conclusion EA in combination with EPO is safe and effective in treating patients with HH. Prospective studies comparing this therapeutic option to phlebotomy are warranted. J. Clin. Apheresis, 2016. © 2016 Wiley Periodicals, Inc.

Background Transfusions prevent a number of complications of sickle cell disease (SCD), but cause inevitable iron loading. With magnetic resonance imaging (MRI), liver iron can be monitored noninvasively. Erythrocytapheresis can limit iron loading and oral chelation provides a more tolerable alternative to subcutaneous administration. The impact of these factors on control of iron burden in SCD has not been well studied. Procedure Iron monitoring practices, chelation use, and transfusion methods were assessed in our cohort of pediatric patients with SCD receiving chronic transfusion. The impact of these factors on iron burden was assessed. Results Among 84 subjects, the proportion that underwent appropriate liver iron concentration (LIC) assessment rose from 21% before to 81% after implementation of R2-MRI in 2006. Among subjects with at least two R2-MRI examinations, median LIC improved (13.2–7.9 mg/g dw, P = 0.027) from initial to final study. Most (67.9%) subjects initially received simple transfusions and subsequently transitioned to erythrocytapheresis. After switching, LIC improved from 13.1 to 4.3 mg/g dw (P

BACKGROUND Chronic exchange transfusion is effective for primary and secondary prevention of stroke in children with sickle cell anemia (SCA). Erythrocytapheresis is recognized to be the most efficient approach; however, it is not widely implemented and is not suitable for all patients. The aim of our study was to compare automated exchange transfusion (AET) with our manual method of exchange transfusion and, in particular, to evaluate the efficacy, safety, and cost of our manual method. STUDY DESIGN AND METHODS Thirty-nine SCA children with stroke and/or abnormal findings on transcranial Doppler were included in the study. We retrospectively analyzed 1353 exchange sessions, including 333 sessions of AET and 1020 sessions of manual exchange transfusion (MET). RESULTS Both methods were well tolerated. The median decrease in hemoglobin (Hb)S per session was 21.5% with AET and 18.8% with our manual method (p

BACKGROUND Chronic transfusion therapy (CTT) is indicated for stroke prevention in children with sickle cell anemia (SCA) and is complicated by iron overload and alloimmunization. CTT is performed by simple transfusion (ST), partial manual exchange (PME), or erythrocytapheresis (RCE). Although small case series have demonstrated RCE in combination with iron chelation therapy stabilizes and/or decreases ferritin, there are no reports comparing the effect of ST, PME, and RCE on liver iron concentration (LIC). CTT modality effect on serum ferritin and LIC were compared in SCA patients on iron chelation, with hemoglobin (Hb)S goal of 30%. STUDY DESIGN AND METHODS Medical records of SCA patients on CTT and deferasirox (≥25 mg/kg/day) were retrospectively reviewed. Mean HbS%, change in ferritin and LIC, and alloimmunization rate were determined for each CTT group. RESULTS Twenty-eight patients were included; six crossed over (one from ST to PME, one from ST to PME then to RCE, three from ST to RCE, and one from PME to RCE) to include 36 transfusion modality intervals. Median pretransfusion HbS% levels were 32.7% (ST), 36.2% (PME), and 34.7% (RCE; p = 0.732). Median ferritin changes were +15 (−17 to +45), +38 (+24 to +105), and −91 (−141 to −48) ng/mL/month (p = 0.003), and median LIC changes (available in 22 patient transfusion modality intervals) were +1.3 (−1.6 to +4.3), +2.3 (−6.5 to +8.9), and −5.7 (−10.7 to −0.5) mg/g/year (p = 0.024) in ST, PME, and RCE, respectively. There was no significant difference in alloimmunization rate between ST/PME and RCE groups. CONCLUSION We recommend RCE plus chelation as an effective method for reducing iron overload, while maintaining HbS at 30% to 35%.

Current treatment for newly diagnosed patients with hereditary hemochromatosis (HH) and iron overload consist of weekly phlebotomy or less frequent and more personalized erythrocytapheresis. Previous observations during phlebotomy suggest an increase in intestinal iron uptake caused by lowering of hepcidin as a result of intensive bloodletting. It is not known whether such an effect is present or even more pronounced using erythrocytapheresis since a larger amount of iron is extracted per procedure. In this study we aimed to assess the effect of erythrocytapheresis on the course of iron parameters, with special focus on serum hepcidin. We performed a retrospective proof-of-principle observational study, comparing serum iron parameters in 12 males during the depletion phase using either phlebotomy (n = 6) or erythrocytapheresis (n = 6). Decreases in serum ferritin over time were similar for both treatments but more pronounced using erythrocytapheresis when expressed per treatment procedure. Hemoglobin did not change during erythrocytapheresis, whereas during phlebotomy decreased with 10%. Increase of erythropoietin and soluble transferrin receptor and decrease in transferrin saturation were similar for both treatments. Reduction in serum hepcidin was higher (50% versus 25% of initial value) and occurred more early using phlebotomy (10 versus 20 weeks after start). In aggregate, compared to phlebotomy, the less frequent and more personalized erythrocytapheresis leads to a more pronounced decrease in serum ferritin per treatment procedure, without a larger decrease in serum hepcidin. This may be clinically relevant and may prevent an increase in intestinal iron uptake and an ensuing vicious circle of more frequent treatment procedures. J. Clin. Apheresis 31:564-570, 2016. © 2015 Wiley Periodicals, Inc.

Background Securing adequate vascular access is essential for a successful apheresis procedure. In most, peripheral access is preferred but it is not always technically possible. Ultrasound-Guided Peripheral Vascular Access (USG-PIVA) is a well-documented technique in the setting of Emergency departments. However, limited data exists reporting its use in the context of automated red cell exchanges (a-RCEx). Purpose To assess the effectiveness and feasibility of USG-PIVA to undertake successful a-RCEx. Methods Data was collected prospectively from patients with sickle cell disease and difficult venous access, undergoing a-RCEx at a single centre. The USG-PIVA technique was attempted and data relating to each attempt was collected and analysed. Results Between April 2014 and July 2015 84 USG-PIVA procedures were performed on 38 patients. 71 USG-PIVA (85%) were successful, 13 (15%) were unsuccessful. Veins successfully cannulated: in the upper arm, basilic (22), brachial (33) and cephalic (2) veins; in the antecubital fossa, basilic (3) and median cubital (7) and in the lower arm, cephalic (2) and radial (2). Cannulas used: Introcan Safety® Braun 22 g (1), 20 g (9) and 18 g (61). Inlet flow rates achieved: 30–60 ml/min (mean 45 ml/min). Depth of veins cannulated: 2–12 mm (mean 5 mm). two complications were observed—one cannula displacement and one nerve injury. No arterial punctures occurred. Central Venous Catheters avoided (49). Conclusion The US-PIVA method offers an effective alternative to Central Venous Access in patients requiring a-RCEx procedures who lack visual or palpable peripheral access, with minimal complications seen in this series. J. Clin. Apheresis 31:501–506, 2016. © 2015 Wiley Periodicals, Inc.

Dysmetabolic iron overload syndrome is a rare event causing hepatic impairment with serious long-term side effects. Here, we describe a case of metabolic syndrome-related hepatic iron overload that showed a rapid, effective, and safe response to erythrocytapheresis. J. Clin. Apheresis 31:443-447, 2016. © 2015 Wiley Periodicals, Inc.

BACKGROUND Phlebotomy is standard maintenance treatment of patients with hereditary hemochromatosis (HH). Erythrocytapheresis, which selectively removes red blood cells, provides a new, potentially more effective treatment option. Our aim was to evaluate the effectiveness of erythrocytapheresis over phlebotomy for maintenance therapy in patients with HH. STUDY DESIGN AND METHODS We conducted a two-treatment-arms, randomized, crossover clinical trial, involving 46 patients, treated for 1 year with either erythrocytapheresis or phlebotomy to keep the ferritin level at not more than 50 µg/L. After 1 year, patients were switched to the other treatment modality. Primary endpoint was the number of treatment procedures per treatment year. Secondary endpoints were intertreatment intervals, several aspects of health-related quality of life, costs, and patient discomfort as well as preference for one of both treatments. RESULTS The mean number of required treatment procedures per treatment year was significantly higher using phlebotomy versus erythrocytapheresis (3.3 vs. 1.9; mean difference, 1.4; 95% confidence interval, 1.1-1.7). The median intertreatment time was 2.3 times longer for erythrocytapheresis. There was no significant difference in overall health assessed by SF-36 and EQ-5D, respectively, between both treatments arms. The number of self-reported swollen joints was significantly higher during phlebotomy treatment. The mean treatment costs of one treatment year were 235€ for phlebotomy versus 511€ for erythrocytapheresis. Eighty percent of patients preferred erythrocytapheresis as treatment method. CONCLUSION Erythrocytapheresis significantly reduced the number of treatment procedures per treatment year, although the mean treatment costs per year are higher in our health care system. It is the preferred treatment for the majority of patients.

BACKGROUND Pregnancy represents a challenge for women with sickle cell disease (SCD), with higher rates of both maternal and fetal complications. The aim of this study was to evaluate the impact of prophylactic transfusion support administered specifically to pregnant women with sickle hemoglobin C disease. MATERIALS AND METHODS Patients were divided into two groups according to the type of transfusion support received: 10 women received prophylactic erythrocytapheresis or manual exchange transfusion at 28 weeks of gestation, and 14 received transfusions only on demand, due to acute complications, or received no transfusions at all. RESULTS Our results indicated higher frequencies of SCD-related complications in the group that did not receive prophylactic transfusion support (35.7% vs. only 10% in the erythrocytapheresis group). Furthermore, these complications were more severe in this group and included all cases of acute chest syndrome. A significant difference was observed concerning gestational age at birth (38.7 weeks in the transfusion group vs. 34.4 weeks, p = 0.037), with a higher frequency of preterm births in the nontransfused group (69.23% vs. 30% in the transfusion group). CONCLUSION We demonstrated a clear reduction of unfavorable outcomes in patients receiving prophylactic transfusions, probably reflecting better maternal and fetal conditions, which corroborated to the more satisfactory indices of vitality, observed in newborns. Considering that erythrocytapheresis or manual exchange transfusions both represent feasible and safe procedures, they could represent important tools for the optimal management of these patients.

Background This study aims to compare in patients with sickle cell disease (SCD), the technical performance and packed red blood cell unit consumption between the automated depletion/Red Blood Cell exchange (RBCx) program (Spectra Optia Apheresis System) with the isovolemic hemodilution (IHD)/RBCx procedure (COBE Spectra Apheresis System) in a routine clinical setting. Methods We retrospectively reviewed the data of 23 patients treated between October 2010 and August 2013 who underwent repeated RBCx on both apheresis systems for preventive indications. Each patient was their own control and had undergone two procedures on each system, totaling 46 sessions per group. On Spectra Optia, we performed the automated depletion/RBCx program. For COBE Spectra, we used a modified IHD/RBCx protocol. All patients had an initial 250 mL depletion offset by a 5% albumin prior to the exchange procedure, for the respective device, with leucodepleted Rh/Kell compatible and cross-matched RBC packs. Results All procedures were well tolerated except three mild febrile nonhemolytic reactions. Postprocedure hemoglobin S (HbS), fraction of cells remaining (FCR), procedure duration and processed blood and anticoagulant volumes were comparable in the two groups. However, the RBCx volume was significantly higher for the Spectra Optia group (+71 mL, P = 0.01), with no significant difference in the number of RBC units used. Conclusions Technical performance and packed RBC unit consumption were not compromised when switching from the COBE Spectra IHD/RBCx protocol to the depletion/RBCx protocol on the Spectra Optia. Tolerability was equal for both protocols. J. Clin. Apheresis 31:429–433, 2016. © 2015 Wiley Periodicals, Inc.

Chronic red blood cell (RBC) transfusion is employed for a wide range of sickle cell disease complications, ranging from primary and secondary stroke prophylaxis to prevention of painful vaso-occlusive episodes. Currently different methods are employed by centers for chronic transfusion that include simple, automated and partial manual RBC exchange transfusion. A retrospective cohort study of two different manual RBC exchange transfusion methods was conducted between two comprehensive care centers in Toronto, ON, Canada and London, United Kingdom in 19 and 21 sickle cell disease adults, respectively. London used a weight-based protocol, while Toronto used a unit-based method. Our results indicated that sickle cell disease patients utilizing a weight-based method are more often unable to achieve the prescribed Hb S (HBB: c.20A T) target compared to the unit-based method (90.0 vs. 53.0% in the weight-based and unit-based methods, respectively, p = 0.0123). On multivariable logistic regression, none of the covariates examined was found to influence the ability to achieve the prescribed Hb S target after accounting for the exchange transfusion method. Mean interval of exchange sessions, session duration, total units of packed RBC, volume of blood used by body weight each year, the mean post exchange hematocrit [or packed cell volume (PCV)] and ferritin change were similar in both cohorts. In conclusion, the unit-based method was more effective at maintaining the prescribed Hb S target.

Cytapheresis (removal of cellular blood components) has been employed for treatment of infectious diseases since the 1960s. Techniques have included thrombocytapheresis (buffy coat apheresis) for loiasis, erythrocytapheresis for malaria and babesiosis, and leukocytapheresis for pertussis-associated lymphocytosis. Published data on these applications is largely limited to case level data and small observational studies; as such, recommendations for or against the use of cytapheresis in the treatment of infections have been extrapolated from these limited (and at times flawed) data sets. Consequently, utilization of cytapheresis in many instances is not uniform between institutions, and typically occurs at the discretion of treating medical teams. This review revisits the existing literature on the use of cytapheresis in the treatment of four infections (loasis, malaria, babesiosis, and pertussis) and examines the rationale underlying current treatment recommendations concerning its use.

The primary function of red blood cells (RBCs) is to deliver oxygen from the lungs to tissues. Tissue hypoxia occurs when the oxygen-carrying capacity of RBCs is compromised due primarily to 3 causes: (1) a reduction in circulating RBC mass, (2) an increase in circulating RBC mass, or (3) abnormal hemoglobin (Hb) that either does not sufficiently release oxygen to tissues (high-oxygen-affinity hemoglobin) or occludes the microvasculature due to deformed RBCs (sickled RBCs). To improve oxygenation in patients with reduced or increased RBC mass, RBC administration (simple transfusion) or RBC removal (RBC depletion) is performed, respectively. However, for patients with abnormal Hb, RBCs containing abnormal Hb are removed and replaced by healthy volunteer donor RBCs by red cell exchange (RCE). RCE can be performed by manual exchange or by automated exchange using a blood cell separator (erythrocytapheresis). In this review, indications for RCE in sickle cell disease using the evidence-based American Society for Apheresis categories1 are presented and the rationale for RCE in each disorder are discussed. Simple transfusion versus RCE and manual RCE versus automated RCE are compared. Finally, this review briefly presents some of the challenges of performing erythrocytapheresis in small children and discusses various choices for central venous access during RCE.2

Apheresis can remove pathogens and mediators that contribute to pathogenic inflammatory responses in diseases not generally considered to be "Hematologic." Erythrocytapheresis can remove intracellular pathogens such as Babesiosis. Plasmapheresis can remove mediators of the inflammatory response in conditions such as sepsis, chronic autoimmune urticaria and malignant pertussis. Leukapheresis can remove potentially harmful leukocytes in Crohn's Disease and malignant pertussis. While apheresis can remove all of these substances, the clinical efficacy and pathophysiologic changes that occur during apheresis in these conditions are largely unknown. Hence, the clinical utility of apheresis in these conditions is largely unknown and research in these areas has the potential to benefit many patients with a variety of diseases.

Background Sickle cell disease (SCD) has become a major public health issue. Hydroxyurea and red blood cell (RBC) transfusion are the cornerstone treatments. Erythrocytapheresis (ECP) is an automated method for transfusion exchange. Given that ECP requires more blood than conventional transfusion, there is concern about alloimmunization and hemolytic transfusion reactions. We evaluate the incidence of hemolytic transfusion reactions and alloimmunization rates in patients receiving conventional blood transfusions and in patients participating in long-term blood exchange programs with ECP. Study Design and Methods All hemolytic transfusion reactions and alloimmunizations in SCD patients were recorded over the period 2006 to 2011. Conventional transfusions and ECP were compared. Results The cohort consisted of 188 SCD patients. The median (±SD) age was 23 (±14) years. The ECP and conventional transfusion groups comprised 49 and 139 patients, respectively. The prevalence of alloimmunization was 33% in the ECP group and 22% in the conventional transfusion group (p = 0.1797). The alloimmunization/RBC unit (RBCU) ratio was lower in the ECP group than in the conventional transfusion group (1.6 and 11.6 per 1000, respectively; p

Background Children with sickle cell disease (SCD) lag in weight and height and have a delayed growth spurt compared to normal children. We studied the effect of long-term erythrocytapheresis (LTE) on the growth of children with SCD and the age at which they attained peak height velocity. Procedure A retrospective chart review was performed recording weight, height, and body mass index (BMI) measurements of 36 patients with SCD who received LTE every 3–5 weeks for an average duration of 5 years. The z-scores for weight, height, and BMI of these patients were compared with that of patients with SCD from the Cooperative Study of Sickle Cell Disease (CSSCD) and a sub-set of 64 controls matched for age, sex, and initial growth parameter z-scores at the start of LTE. Results The z-scores for all parameters improved significantly for our patients on LTE compared to match controls from CSSCD and the entire pediatric CSSCD cohort (P-value

Using patients with polycythemia vera (PV) as an experimental model, we evaluated the impact of clot retraction (CR) and architecture of the clot on fibrinolysis. We studied the kinetics of clot retraction and the fibrinolysis rate in whole blood from 48 PV patients and 48 healthy controls. Measurements were performed before and after isovolemic eryhrocytapheresis (ECP). CR was measured by optical method. Clot lysis time (CLT) and maximum clot firmness (MCF) were measured by thromboelastometry in recalcified blood supplemented with t-PA and tissue factor. Compared with healthy controls, CR rate in PV patients was higher (0.0219 vs. 0.0138; p0.001), the clot volume smaller and MCF elevated (64 vs. 58 mm). CR rate correlated with platelet count (r=0.546; p=0.001) but not with erythrocyte concentration (r=0.192; p0.3). Compared with healthy controls, CLT in PV patients was significantly prolonged (158 min vs. 71 min). Fibrinolysis rate inversely correlated with CR rate (r=-0.566; p0.001); MCF (r=-0.704; p0.001) and platelet count (r=-0.461; p0.001). As judged by confocal microscope, in comparison to healthy controls, clots formed in blood from PV patients demonstrated booth a distinctly higher degree of crosslinking and possessed thinner fibers. Altered CR, MCF and fibrinolysis speeds were not normalized following the ECP procedure. Tirofiban (a blocker of platelet GPIIb/IIIa receptors), unlike aspirin, normalized abnormal CR and fibrinolysis in blood from PV patients. Collectively, our data indicate that in PV patients, abnormal CR may result in formation of thrombi that are more resistant to fibrinolysis. ECP and aspirin failed to normalize platelet-related fibrinolysis resistance.

Background and Objectives Erythrocytapheresis and leukapheresis (LPE) of small children are logistically complex and many centres are reluctant to perform these procedures. In children, both sickle cell and leukaemic emergencies demand prompt action to prevent additional morbidity but detailed protocols for small children are lacking, and often are performed using guidelines shown to work in larger patients. We report a 3-year experience with children weighing 11–25 kg at a large academic medical centre. Materials and Methods All patients were treated with the COBE® Spectra apheresis system; circuit was primed with blood not adjusted for haematocrit and anticoagulant citrate dextrose A was used as anticoagulation. Procedures were performed in the paediatric intensive care unit by apheresis nursing staff. Results Twenty-five apheresis procedures in 19 patients were performed; 17 of 19 patients presented with sickle cell-related acute complications and two (2/19) with newly diagnosed acute leukaemia and hyperleucocytosis. None of the patients required medications during the procedures. Vital signs and clinical condition remained stable and did not worsen during or postapheresis. One patient had a delayed haemolytic transfusion reaction 1 week posterythrocytapheresis as he developed alloantibodies as a result of the procedure. All sickle cell patients achieved a target haematocrit of 21–30% and Haemoglobin A of ≥68%. Both leukaemia patients who underwent LPE had no further signs of leukostasis and achieved marked reductions in leucocyte counts. Conclusions Apheresis of children weighing 11–25 kg can be safely performed without increased morbidity. We outline a protocol that can be used to perform apheresis with minimal complications.

We compared preoperative autologous blood donation (PABD) using serial manual whole blood (WB) and PABD using a single session, double-unit erythrocytapheresis in terms of the hemodynamic recovery and clinical outcomes.This study included 56 donors in the WB PABD group and 117 donors in the double-unit erythrocytapheresis PABD group. All subjects were men with body weight70 kg, Hb level13.3g/dL, Hct40%, and who were scheduled for oral and maxillofacial surgery. Three cycles of manual WB collection for PABD or a single session, double-unit erythrocytapheresis using the Alyx was performed.There were no significant differences in donor demographic variables including age, height, weight, Hb, Hct, or red cell mass between the 2 groups. The double-unit erythrocytapheresis was completed earlier than the last manual WB PABD (at 15.3 ± 4.7 days and 6.5 ± 3.2 days before surgery, p0.001). Hct values before surgery were higher in the double-unit erythrocytapheresis PABD group than in the manual WB PABD group (39.7 ± 3.2 vs. 38.6 ± 2.7, p=0.024). ΔHct and %ΔHct before the first PABD and before surgery were lower in the double-unit erythrocytapheresis PABD group than in the manual WB PABD group (-5.6 ± 2.8 vs. -6.8 ± 2.7, p=0.010 and -12.3 ± 5.9 vs. -14.8 ± 5.6, p=0.008, respectively). The incidence of additional allogeneic blood transfusions during or after surgery and the post-operative Hb and Hct values were similar in the 2 groups. The length of hospital stay after surgery was significantly longer in the manual WB PABD group than in the double-unit erythrocytapheresis group (6.1 ± 2.5 vs. 5.4 ± 1.9, p=0.043). Of the 33 donors in the double-unit erythrocytapheresis PABD group, 7 (21.2%) reported discomforts related to the procedure, and 6 graded the discomforts (hypocalcemia, perioral tingling sense, paresthesia, dizziness, stuffiness, pain on the intravenous site, and muscle tension) as mild.The single session, double-unit erythrocytapheresis prolonged the time interval between PABD and surgery and led to better hemodynamic recovery than the serial manual WB PABD, and hypocalcemic symptoms were mild.

Background and Objectives We describe the recognition and pattern of care of voluntary blood donors with early-uncomplicated genetic haemochromatosis in our blood donation centre. Materials and Methods Asymptomatic volunteers with suspicion of hereditary haemochromatosis (HH) due to an elevated ferritin level on routine screening were referred for further investigation. Alternatively, we accepted subjects with prediagnosed HH on referral. In the case of early-uncomplicated genetic haemochromatosis, either standard whole blood donation (WBD) or double-erythrocytapheresis (DEC) was offered. Results A median of six procedures was needed to achieve a ferritin value below 100 ng/ml in the WBD group and of four in the DEC group (P = 0·5). The rate of donation side-effects was higher in the DEC group, while the costs it generated were equivalent to WBD. Conclusion Compared with WBD, DEC had no beneficial effect on treatment number, length of treatment, side-effects or treatment budget in early-uncomplicated HH. Integrating donors with uncomplicated genetic haemochromatosis to blood donation programmes can supplement blood stores and provide the donors with a cost-effective and altruistic purpose of treatment.

Children and adolescents with sickle cell disease (SCD) are at high risk of strokes and are frequently treated with red blood cell (RBC) transfusions. The goal is to suppress hemoglobin (Hb) S while minimizing transfusion-induced iron overload. RBCs may be given via simple transfusion, manual exchange transfusion (MET), or erythrocytapheresis (aRBCX). Chronic transfusion practices vary among institutions.This single-institution, retrospective cohort study compares Hb S control and therapy complication rates between MET and aRBCX in a cohort of children and adolescents with SCD and stroke during a 5-year period from 2008 through 2012. Duration and mode of transfusion therapy, achievement of Hb S suppression goal, iron burden by ferritin levels, and catheter complications were evaluated.Thirty-seven children were included in analysis. The prevalence of catheter complications was 75% in aRBCX recipients compared with 0% in MET recipients (P0.001). There was no significant difference between modalities in achieving Hb S suppression or ferritin goals, but those receiving aRBCX had a greater likelihood of discontinuing chelation therapy. Among aRBCX recipients, adherence to90% of transfusion appointments was associated with achieving Hb S suppression goals.aRBCX may have increased complication risks compared with MET for chronic transfusion therapy in SCD. Risks and benefits of aRBCX and MET should be considered when selecting a chronic transfusion modality. Transfusion therapy modalities should be compared in prospective studies for stroke prevention in children with SCD.

A number of disorders cause iron overload: some are of genetic origin, such as hereditary haemochromatosis, while others are acquired, for instance due to repeated transfusions. This article reviews the treatment options for hereditary haemochromatosis, with special attention to the use of erythrocytapheresis. In general, therapy is based on the removal of excess body iron, for which ferritin levels are used to monitor the effectiveness of treatment. For many decades phlebotomy has been widely accepted as the standard treatment. Recent publications suggest that erythrocytapheresis, as a more individualized treatment, can provide a good balance between effectiveness, tolerability and costs. Other treatments like oral chelators and proton pomp inhibitors, which are used in selected patients, create the possibility to further individualize treatment of hereditary haemochromatosis. In the future, hepcidin-targeted therapy could provide a more fundamental approach to treatment.

Therapeutic apheresis is an extracorporeal blood purification technique designed for the removal of either plasma (plasmapheresis) or cellular blood components (cytapheresis). One of the main indications for the use of apheresis is in the treatment of the hyperviscosity syndromes that can result from either the presence of abnormal plasma components, such as antibodies, immune complexes, paraproteins, and cryoglobulins, or the excessive increase in blood cells as seen in polycythemia, leukemias, and myeloproliferative diseases. Apheresis involves withdrawal of anticoagulated blood via a vascular catheter, separation of different blood components by either centrifugation or membrane filtration, removal of the undesired component, and reinfusion of the remaining components with replacement fluid into the patient. The centrifugal method can be intermittent or continuous, the latter being faster and fully automated, and is principally used in North America. The membrane filtration technique, mainly used in Europe and Japan, involves the filtration of blood by filters of different pore sizes. These are used sequentially in a process called double or cascade filtration, enabling removal of specific plasma pathogens without need for replacement fluids. In paraproteinemias, hyperviscosity syndrome is most commonly seen with Waldenstrom's macroglobulinemia, followed by immunoglobulin (Ig) A and IgG (3) multiple myeloma. Single plasmapheresis with one plasma volume replacement (about 3 L) usually results in a dramatic improvement in patients with macrogobulinemia because of its predominant intravascular distribution, whereas repeated plasmapheresis is necessary with other types of paraproteins. Cryofiltration apheresis using a high-capacity cryofilter is specific for the removal of cryoglobulins. In leukemias with hyperleukocytosis, there are no evidence-based guidelines for use of leukapheresis, but it is commonly initiated when white blood cells (WBC) are > 100,000/microL or even with lower counts if leukostasis symptoms are present, especially in acute myeloid leukemia. Erythrocytapheresis and plateletpheresis are mostly used in the acute management of symptomatic patients with polycythemia vera (PV), essential thrombocytosis, and sickle cell disease.

We investigated the correlation between body weight index (BWI) and the effective power of erythrocytapheresis in patients with polycythemia vera (PV) who received therapeutic erythrocytapheresis (TEA). Furthermore, the risk factors of the adverse events related to erythroapheresis therapy were analyzed. Two hundred and seventeen cycles of therapeutic erythrocytapheresis were carried out in 139 patients with PV (Hct). The correlation between the BWI and the difference of hematocrit before and after therapeutic erythrocytapheresis (ΔHct) was analyzed by the Pearson correlation analysis method. Logistic regression analysis was used to study the risk factors of adverse events for TEA. We observed a positive correlation between the BWI and ΔHct. BWI over 15 ml/kg, inlet velocity of the apheresis procedure over 45 ml/min and an age older than 50 years were the risk factors of adverse events of TEA. The results suggested that BWI was a sensitive index to estimate the effective power and adverse events of TEA. The rate of adverse events of TEA might be reduced by maintaining the BWI below the dangerous threshold of 15 ml/kg and the inlet velocity of the apheresis procedure below 45 ml/min especially in patients older than 50 years of age.

OBJECTIVES The study sought to assess the potential utility of impedance cardiography (ICG) to detect hemodynamic changes after erythrocytapheresis in stable children with sickle cell disease (SCD). METHODS We prospectively monitored cardiac index, systemic vascular resistance index, heart rate, and blood pressure using ICG before and after erythrocytapheresis in 26 stable children with SCD. Echocardiography was carried out in all patients to evaluate left ventricular systolic function. Hemoglobin (Hb), sickle cell hemoglobin (HbS), and ferritin levels were also measured. RESULTS Of a total of 78 erythrocytapheresis procedures in 26 children with SCD, 22 (28.2%) had hypotensive episodes defined as a decrease in systolic, diastolic, or mean blood pressure by 10 mmHg. Risk factors for developing hypotension during erythrocytapheresis were identified with logistic regression analysis: lower-body surface area and decrease in cardiac index. In contrast, age, prepheresis Hb and HbS, serum ferritin levels, and left ventricular function at baseline were not associated with hypotension. CONCLUSIONS This study demonstrates the feasibility of the ICG technique to detect the hemodynamic changes in children with SCD after an erythrocytapheresis procedure.

BACKGROUND: Erythrocytapheresis (ECP), automated red blood cell exchange, is increasingly being used for chronic transfusion therapy in sickle cell disease (SCD) as it is an isovolumetric transfusion, is more effective in lowering hemoglobin (Hb)S, and can limit iron overload. Because ECP requires increased blood exposure compared to simple transfusions there is concern for increased transfusion complications, including alloimmunization. We compared alloimmunization rates between patients receiving simple or exchange chronic transfusions. STUDY DESIGN AND METHODS: Data were retrospectively collected for 45 SCD patients (n = 23 simple, n = 22 ECP) on a chronic transfusion program as of December 2010 to determine the rate of antibody formation (antibodies formed per 100 units transfused). RESULTS: The 45 patients received 10,949 units and formed six new alloantibodies during the study period (1994-2010); therefore, the overall alloimmunization rate was 0.055 alloantibodies per 100 U. There were three antibodies formed in three patients on ECP, one allo (anti-rhi) and two autoantibodies. There were six antibodies in four patients on a simple transfusion program, five allo (anti-Lea, M, D, C, and Kpa) and one autoantibody. The ECP group received significantly more blood (338.5 units/patient vs. 152.2 units/patient, p = 0.001). The rate of antibody formation (auto plus allo) was 0.040 antibodies per 100 U in the ECP group and 0.171 antibodies per 100 U in the simple transfusion group (p = 0.04). The alloantibodies formed per 100 units was 0.013 in the ECP group and 0.143 in the simple transfusion group (p = 0.03). CONCLUSION: Chronic ECP should be considered in patients requiring optimal management of HbS levels and iron burden. Concerns about increased alloimmunization with ECP may be unjustified.

BACKGROUND: Standard treatment of newly diagnosed HFE hemochromatosis patients is phlebotomy. Erythrocytapheresis provides a new therapeutic modality that can remove up to three times more red blood cells per single procedure and could thus have a clinical and economic benefit. STUDY DESIGN AND METHODS: To compare the number of treatment procedures between erythrocytapheresis and phlebotomy needed to reach the serum ferritin (SF) target level of 50 microg/L, a two-treatment-arms, randomized trial was conducted in which 38 newly diagnosed patients homozygous for C282Y were randomly assigned in a 1:1 ratio to undergo either erythrocytapheresis or phlebotomy. A 50% decrease in the number of treatment procedures for erythrocytapheresis compared to phlebotomy was chosen as the relevant difference to detect. RESULTS: Univariate analysis showed a significantly lower mean number of treatment procedures in the erythrocytapheresis group (9 vs. 27; ratio, 0.33; 95% confidence interval [CI], 0.25-0.45; Mann-Whitney p < 0.001). After adjustments for the two important influential factors initial SF level and body weight, the reduction ratio was still significant (0.43; 95% CI, 0.35-0.52; p < 0.001). Cost analysis showed no significant difference in treatment costs between both procedures. The costs resulting from productivity loss were significantly lower for the erythrocytapheresis group. CONCLUSION: Erythrocytapheresis is highly effective treatment to reduce iron overload and from a societal perspective might potentially also be a cost-saving therapy.

This article reviews advances in the scientific basis and medical practice of plasmapheresis and cytapheresis therapies. Newly-characterized autoantibodies in neuromyelitis optica, Guillain-Barre variants, anti-neutrophil cytoplasmic antibody (ANCA) vasculitides, etc., exemplify the modern molecular biology which now provides a rigorous framework of understanding for the clinical practice of plasmapheresis. Clinical trials continue to clarify the appropriate use of therapeutic plasmapheresis (TPE) in these and other diseases. Centrifugal (cTPE) and membrane filtration (mTPE) types of plasmapheresis are compared, with details of the plasmapheresis prescription, anticoagulation choices, replacement fluids and other practical considerations. Plasma removal is more efficient with cTPE; mTPE systems have a lower plasma extraction ratio, and therefore require higher blood flow rates or longer procedure times. Autoantibodies and other pathogenic macromolecules targeted for removal by plasmapheresis can be depleted predictably when the plasma is discarded, as in conventional TPE. On-line plasma processing to regenerate the patient’s own plasma avoids the need for replacement albumin solutions or plasma transfusion, but is inherently less efficient at removing the target molecule, so usually requires a longer procedure. Therapeutic white cell reduction (leukapheresis), platelet reduction (thrombocytapheresis) and red cell exchange (erythrocytapheresis) require centrifugal apheresis systems. J. Clin. Apheresis 26:230–238, 2011. V C 2011 Wiley-Liss, Inc.

Venous thromboembolism (VTE) is being increasingly recognized in children with sickle cell disease (SCD). In a retrospective cohort study, we identified bilateral central venous catheter (CVC) placement as an independent risk factor for VTE. At our institution, the only indication for bilateral CVC placement in children with SCD is erythrocytapheresis. To investigate the impact of erythrocytapheresis on coagulation, we measured levels of natural anticoagulants in 11 patients with SCD on chronic erythrocytapheresis, immediately before and after apheresis. We demonstrated a statistically significant reduction in most parameters. Additional studies are needed to further investigate the exact etiology and clinical impact of this acute decrease.

Background Erythrocytapheresis, or red blood cell exchange transfusion (RBCX), with donor red blood cell (RBC) units is now increasingly used in the treatment of acute and chronic complications of sickle cell disease (SCD). As in all transfusions, RCBX carries a risk of immunization against foreign antigen on transfused cells. However, by selecting donor units with RBC phenotypes similar to the patient, the risk of allo- and autoimmunization can be reduced. Procedure The formation of RBC alloantibodies and/or autoantibodies in 32 multitransfused pediatric SCD patients undergoing monthly RBCX over a 11-year period (12/1998 to 12/2009) was evaluated utilizing a retrospective patient chart review at Kosair Children's Hospital, Louisville, Kentucky. Results After starting C, E, K antigen-matched RBCX, the rate of clinically significant allo-immunization decreased from 0.189/100 to 0.053/100 U, with a relative risk of 27.9%. Likewise, the rate of autoimmunization decreased from 0.063/100 to 0.035/100 U, with a relative risk of 55.9%. Conclusion After controlling for clinically insignificant antibodies, our auto- and alloimmunization rate was much less than previously reported values. In addition, the incidence of clinically significant allo- and autoimmunization decreased in our patient population after starting minor antigen-matched RBCX. These results suggest that by matching selected RBC phenotypes, there may be an association in the risk of allo- and autoimmunization of multi-transfused SCD patients. Pediatr Blood Cancer. 2010;55:1134–1137. © 2010 Wiley-Liss, Inc.