RESUMO
INTRODUCTION: Peripheral blood stem cell (PBSC) collection via apheresis requires the administration of granulocyte colony-stimulating factor (filgrastim) to stem cell donors. Several reports have shown that filgrastim administration and apheresis procedure induce a hypercoagulable state across PBSC collection, which might predispose certain donors to thrombotic complications. METHODS: We evaluated the hemostatic functions of healthy allogeneic stem cell donors by rotational thromboelastometry (ROTEM). Blood samples from healthy donors (n = 30) were collected at defined time points: before filgrastim (baseline), on the day of apheresis before and after the procedure, and 1 week after apheresis. RESULTS: The results indicated that hemostatic changes are temporary since all parameters in both EXTEM and INTEM assays are restored to their initial values 1 week after the apheresis. CONCLUSION: We concluded that stem cell apheresis does not induce a hypercoagulable state in healthy donors. This is the first study evaluating the hemostatic functions of stem cell donors by ROTEM.
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Remoção de Componentes Sanguíneos , Tromboelastografia , Humanos , Tromboelastografia/métodos , Remoção de Componentes Sanguíneos/métodos , Masculino , Feminino , Adulto , Filgrastim/farmacologia , Pessoa de Meia-Idade , Hemostasia/fisiologia , Transplante Homólogo/métodos , Doadores de Tecidos , Adulto JovemRESUMO
BACKGROUND AND OBJECTIVES: We evaluated the operational and safety impact of implementing anaerobic culture screening of apheresis and pooled platelets at the American Red Cross on the already established use of the aerobic culture screening of each donation performed no sooner than 24 h following collection. MATERIALS AND METHODS: Platelets were screened for bacterial contamination with the BACT/ALERT 3D® (bioMérieux, Durham, NC) microbial detection testing system. The addition of anaerobic culture to the already existing aerobic culture resulted in sampling an additional 8-10 mL from each donation. RESULTS: Implementation of anaerobic testing resulted in an approximate 3.5-fold increased rate of False Positive BACT/ALERT alarms. There was a modest increase in the rate of True Positive alarms of 1.4-fold with increased detection of Klebsiella and Propionibacterium species, including Cutibacterium acnes. In addition, there was an approximate 3.5-fold increase rate of False Positives and a 13.5-fold increase rate of Indeterminates, the majority (~57%) were due to Cutibacterium acnes. The combined costs and lost revenue associated with adding anaerobic screening increased by ~$1,000,000/year due to testing cost and product discards. CONCLUSION: The addition of anaerobic culture to aerobic culture to the original donation (without the introduction of sampling delay) resulted in a significant increase in the rate of alerts. The 40% increased rate of True Positive alarms may have modestly improved platelet safety. However, there was a disproportionate increase in the rate of False Positive and Indeterminate bacterial culture alarms, which added substantial cost and overall loss of platelet products.
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Remoção de Componentes Sanguíneos , Plaquetas , Humanos , Anaerobiose , Plaquetas/microbiologia , Bactérias , Contaminação de Medicamentos , Técnicas BacteriológicasRESUMO
OBJECTIVES: The US health care payment system is complex and difficult to interpret. Although federal regulations require that more data, in the form of charges and negotiated rates, be made available, compliance remains variable. We review chargemaster and negotiated rate values for extracorporeal photopheresis (ECP) to assess this variability. We sought to determine the availability of chargemaster and negotiated rates for health care consumers and to assess compliance and pricing among institutions using ECP as a model for apheresis billing. METHODS: We obtained ECP chargemaster data and negotiated rates from 20 institutions. We analyzed the availability of ECP chargemaster data and compared values with a previously published historic cohort. We evaluated the availability of negotiated rates and determined relative reimbursement using charge to reimbursement ratios. We determined calculated fines for hospitals based on bed size. RESULTS: Chargemaster availability increased from 2019 to 2022, though only 65% (13/20) of hospitals had both chargemaster and negotiated rate data. Chargemaster prices increased significantly from 2019 to 2022 (range, $3,586.83-$34,043.00). We reviewed 1,191 negotiated rates, with institutions averaging 93.6 different rates (SD, 189.5). Negotiated rates were variable, ranging from $3,586.83 to $34,043.00 per procedure. Reimbursement was higher among private insurers compared with reported Centers for Medicare & Medicaid Services negotiated rates. Of the 35% (7/20) that lacked chargemaster and negotiated rates, institutions faced an average annual fine of $1,430,800. CONCLUSIONS: Despite recent financial penalties, ECP pricing data are often unavailable or inadequate. Current available resources are unlikely to benefit the average health care consumer who requires ECP.
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Remoção de Componentes Sanguíneos , Fotoferese , Idoso , Humanos , Hospitais , Medicare , Pacientes Ambulatoriais , Estados UnidosRESUMO
BACKGROUND: Structural and biochemical changes in stored platelets are influenced by collection and processing methods. This international study investigates the effects of platelet (PLT) processing and storage conditions on HMGB1, sCD40L, and sCD62P protein levels in platelet concentrate supernatants (PCs). STUDY DESIGN/METHODS: PC supernatants (n = 3748) were collected by each international centre using identical centrifugation methods (n = 9) and tested centrally using the ELISA/Luminex platform. Apheresis versus the buffy coat (BC-PC) method, plasma storage versus PAS and RT storage versus cold (4°C) were investigated. We focused on PC preparation collecting samples during early (RT: day 1-3; cold: day 1-5) and late (RT: day 4-7; cold: day 7-10) storage time points. RESULTS: HMGB1, sCD40L, and sCD62P concentrations were similar during early storage periods, regardless of storage solution (BC-PC plasma and BC-PC PAS-E) or temperature. During storage and without PAS, sCD40L and CD62P in BC-PC supernatants increased significantly (+33% and +41%, respectively) depending on storage temperature (22 vs. 4°C). However, without PAS-E, levels decreased significantly (-31% and -20%, respectively), depending on storage temperature (22 vs. 4°C). Contrastingly, the processing method appeared to have greater impact on HMGB1 release versus storage duration. These data highlight increases in these parameters during storage and differences between preparation methods and storage temperatures. CONCLUSIONS: The HMGB1 release mechanism/intracellular pathways appear to differ from sCD62P and sCD40L. The extent to which these differences affect patient outcomes, particularly post-transfusion platelet increment and adverse events, warrants further investigation in clinical trials with various therapeutic indications.
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Remoção de Componentes Sanguíneos , Proteína HMGB1 , Humanos , Remoção de Componentes Sanguíneos/métodos , Plaquetas/metabolismo , Preservação de Sangue/métodos , Ligante de CD40/metabolismo , Proteína HMGB1/metabolismo , Transfusão de PlaquetasRESUMO
OBJECTIVE: We studied the impact of storage of thawed plasma (TP) on the in vitro coagulation quality and posttransfusion outcomes of apheresis plasma (AP) vs whole blood plasma (WBP). METHODS: One hundred units of each product were analyzed. In vitro assays were performed on TP on day 0, day 2, and after refreezing, evaluating international normalized ratio (INR), activated partial thromboplastin time (aPTT), fibrinogen, and factors V and VIII. Transfusion of TP on day 2 was studied in 70 patients with liver cirrhosis and 25 patients with thrombotic thrombocytopenic purpura (TTP). RESULTS: Refrozen specimens from both products showed a significant decline of all values, although AP had a considerably greater coagulation profile (P < .05).On day 0 and day 2, we observed significant decreases in coagulation values (except fibrinogen) with WBP, compared with AP (P < .05). The WBP, however, provided similar INR for patients with liver cirrhosis and TTP, as compared with AP. The AP resulted in a significant correction of aPTT following plasma exchange in TTP (P < .05). CONCLUSION: AP demonstrated considerably greater factor activity. This would be beneficial when manufacturing clotting factor concentrates. Large scale clinical trials are needed to further address the hemostatic outcomes of both products in massively transfused patients.
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Remoção de Componentes Sanguíneos , Púrpura Trombocitopênica Trombótica , Fator V , Fibrinogênio/análise , Humanos , Cirrose Hepática , Plasma/química , Púrpura Trombocitopênica Trombótica/terapiaRESUMO
Treatment for multiple myeloma (MM) can involve apheresis to mobilize hematopoietic stem cells for later autologous stem cell transplantation (ASCT), which can become costly over time. This retrospective claims database study examined healthcare resource use and medical costs associated with plerixafor, a selective CXCR4 inhibitor that mobilizes hematopoietic stem cells and minimizes apheresis times. Medical data were sampled from Japanese MM patients between April 2017 and September 2019, after the Japanese launch of plerixafor. The study population (190 plerixafor users and 180 non-users) was identified from the Medical Data Vision database, and further stratified into those using granulocyte-colony stimulating factor in monotherapy or in combination with cyclophosphamide to trigger apheresis. A descriptive comparison of patient characteristics, healthcare resource use, and medical costs across the mobilization and ASCT phases indicated plerixafor is associated with higher average total medical costs. However, plerixafor-treated patients received fewer concomitant medications and spent less time in apheresis than non-users. A comparison of non-users with a similar analysis conducted pre-plerixafor launch (2013-2017) showed general improvements to treatment independent of plerixafor. The results of this research can inform guidelines for the role of plerixafor in balancing cost-effectiveness and drug efficacy in MM treatment.
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Benzilaminas , Remoção de Componentes Sanguíneos , Ciclamos , Transplante de Células-Tronco Hematopoéticas , Mieloma Múltiplo , Benzilaminas/uso terapêutico , Remoção de Componentes Sanguíneos/métodos , Análise Custo-Benefício , Ciclamos/uso terapêutico , Atenção à Saúde , Fator Estimulador de Colônias de Granulócitos/uso terapêutico , Mobilização de Células-Tronco Hematopoéticas/métodos , Humanos , Japão , Mieloma Múltiplo/tratamento farmacológico , Estudos Retrospectivos , Transplante AutólogoRESUMO
Abstract Introduction Convalescent Plasma therapy is one of the therapeutic strategies that has been used for patients with the Covid-19 disease. Implementing a program with national extension to supply hospitals with this blood component is a great challenge mainly in a middle-income economy. Objectives Our objective was to develop and implement a Covid-19 Convalescent Plasma Program which met established quality standards and was adapted to a reality of limited resources. Methods A multicentric convalescent plasma collection program was developed and implemented, based on four main sequential procedures: selective donor recruitment, pre-donation antibody screening (Anti-SARS-CoV-2- Chemiluminescence IgG Abbott), convalescent plasma collection by apheresis or whole-blood processing and distribution to the hospitals according to local demand. Results From the 572 candidates submitted to the pre-donation antibody screening, only 270 (47%) were considered eligible for plasma donation according to the established criteria. Higher levels of total antibody were associated with the donor age being above 45 years old (p= 0.002), hospital admission (p= 0.018), and a shorter interval between the diagnosis of the SARS-CoV-2 infection and plasma donation (p < 0.001). There was no association between the ABO and Rh blood groups and their antibody levels. Of the 468 donations made, 61% were from the collection of whole-blood and 39%, from apheresis. The Covid-19 Convalescent Plasma units obtained were distributed to 21 different cities throughout the country by air or ground transportation. Conclusion The implementation of a Covid-19 Convalescent Plasma program in a continental country with relatively scarce resources is feasible with alternative strategies to promote lower cost procedures, while complying with local regulations and meeting quality standards.
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Humanos , Masculino , Feminino , Adolescente , Adulto , Pessoa de Meia-Idade , Adulto Jovem , Remoção de Componentes Sanguíneos , Imunização Passiva , COVID-19/terapia , Plasma , SARS-CoV-2RESUMO
BACKGROUND: Platelet transfusion therapy is widely used to prevent hemorrhage in patients with thrombocytopenia and platelet disorders. The platelet concentrate (PC) quality is affected by increased storage time, as reflected in the decreased number of platelets, morphological changes, and impaired functions. This study aimed to analyze the impact of 5 days storage on platelets count and the expression of CD63, and Annexin V as activation markers during PC storage. METHODS: Fifty PCs collected from single donors were tested for platelet count on days 0, 3, and 5 using a Sysmex blood counter. CD61, CD63, and Annexin V expression was analyzed by a multicolor Navios flow cytometer. RESULTS: There was a significant decrease in platelet count during 5 days of storage. There was a direct relationship between storage time and degree of platelet activation. CD63 had almost double increased expression on day 5 than day 3. Annexin V showed significantly increased expression on day 3 with minor differences between days 3 and 5. CONCLUSION: According to standard blood bank conditions, PC stored for 5 days showed a degree of in vitro activation as evidenced by CD63 and Annexin V expression, may lead to reduced therapeutic efficacy. Flow cytometry monitoring platelet activation in PC offers a better understanding of the changes during PC storage and may help improve platelet products.
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Remoção de Componentes Sanguíneos , Neoplasias , Anexina A5/metabolismo , Plaquetas/metabolismo , Preservação de Sangue , Humanos , National Cancer Institute (U.S.) , Transfusão de Plaquetas , Estados Unidos , UniversidadesRESUMO
INTRODUCTION: Supplemental data from the 2019 National Blood Collection and Utilization Survey (NBCUS) are presented and include findings on donor characteristics, autologous and directed donations and transfusions, platelets (PLTs), plasma and granulocyte transfusions, pediatric transfusions, transfusion-associated adverse events, cost of blood units, hospital policies and practices, and implementation of blood safety measures, including pathogen reduction technology (PRT). METHODS: National estimates were produced using weighting and imputation methods for a number of donors, donations, donor deferrals, autologous and directed donations and transfusions, PLT and plasma collections and transfusions, a number of crossmatch procedures, a number of units irradiated and leukoreduced, pediatric transfusions, and transfusion-associated adverse events. RESULTS: Between 2017 and 2019, there was a slight decrease in successful donations by 1.1%. Donations by persons aged 16-18 decreased by 10.1% while donations among donors >65 years increased by 10.5%. From 2017 to 2019, the median price paid for blood components by hospitals for leukoreduced red blood cell units, leukoreduced apheresis PLT units, and for fresh frozen plasma units continued to decrease. The rate of life-threatening transfusion-related adverse reactions continued to decrease. Most whole blood/red blood cell units (97%) and PLT units (97%) were leukoreduced. CONCLUSION: Blood donations decreased between 2017 and 2019. Donations from younger donors continued to decline while donations among older donors have steadily increased. Prices paid for blood products by hospitals decreased. Implementation of PRT among blood centers and hospitals is slowly expanding.
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Doadores de Sangue/estatística & dados numéricos , Pesquisas sobre Atenção à Saúde , Adolescente , Adulto , Distribuição por Idade , Idoso , Bancos de Sangue/estatística & dados numéricos , Remoção de Componentes Sanguíneos/estatística & dados numéricos , Transfusão de Componentes Sanguíneos/estatística & dados numéricos , Transfusão de Componentes Sanguíneos/tendências , Doadores de Sangue/provisão & distribuição , Antígenos de Grupos Sanguíneos/genética , Transfusão de Sangue/estatística & dados numéricos , Transfusão de Sangue/tendências , Transfusão de Sangue Autóloga/estatística & dados numéricos , Transfusão de Sangue Autóloga/tendências , Área Programática de Saúde , Criança , Pré-Escolar , Transmissão de Doença Infecciosa/prevenção & controle , Seleção do Doador/estatística & dados numéricos , Feminino , Custos de Cuidados de Saúde , Hospitais/estatística & dados numéricos , Humanos , Lactente , Recém-Nascido , Procedimentos de Redução de Leucócitos/economia , Procedimentos de Redução de Leucócitos/métodos , Masculino , Pessoa de Meia-Idade , Política Organizacional , Assunção de Riscos , Estudos de Amostragem , Procedimentos Cirúrgicos Operatórios/estatística & dados numéricos , Reação Transfusional/epidemiologia , Estados Unidos/epidemiologia , Adulto JovemRESUMO
OBJECTIVES: We aimed to compare plasmapheresis and medical apheresis as lipid-lowering therapies in children with familial lipoprotein lipase (LPL) deficiency. METHODS: The data of 13 patients who were followed up after a diagnosis of LPL deficiency were retrospectively analyzed. Plasma triglyceride, cholesterol, amylase, and lipase values and complications were recorded before and after each patient underwent plasmapheresis or medical apheresis. RESULTS: The mean follow-up period of the patients was 99.64 ± 52.92 months in the medical apheresis group and 118 ± 16.97 months in the plasmapheresis group. While the mean triglyceride level before plasmapheresis was 1,875.38 ± 547.46 mg/dL, it was 617 ± 228.28 mg/dL after plasmapheresis. While the mean triglyceride level before medical apheresis was 1,756.86 ± 749.27 mg/dL, it was found to be 623.03 ± 51.36 mg/dL after medical apheresis. Triglyceride levels were decreased by 59.62% with medical apheresis and 65.57% with plasmapheresis. The cost of treatment for medical apheresis was found to be lower compared to plasmapheresis 296.93 ± 29.94 Turkish lira (USD 43.34 ± 4.01) vs. 3,845.42 ± 156.17 Turkish lira (USD 561.37 ± 20.93; p<0.001). CONCLUSIONS: Although there is no standardized strategy for the acute treatment of hypertriglyceridemia due to LPL deficiency, medical apheresis is a safe and effective treatment with a low risk of side effects. Unlike plasmapheresis, medical apheresis can be performed in any center, which is another important advantage of the procedure.
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Remoção de Componentes Sanguíneos/métodos , Hiperlipoproteinemia Tipo I/complicações , Hipertrigliceridemia/terapia , Plasmaferese/métodos , Triglicerídeos/sangue , Remoção de Componentes Sanguíneos/economia , Criança , Pré-Escolar , Feminino , Custos de Cuidados de Saúde , Humanos , Hiperlipoproteinemia Tipo I/sangue , Hipertrigliceridemia/sangue , Hipertrigliceridemia/etiologia , Lactente , Recém-Nascido , Masculino , Plasmaferese/economia , Estudos Retrospectivos , Resultado do TratamentoRESUMO
BACKGROUND: This study aims to determine the phlebotomy and procedural outcomes using a vein assessment tool (VAT) in Double Dose Platelet (DDP) collections by apheresis. METHODS: VAT was based on assessing vein visibility, palpation and size with maximum score of 12 and the least being 0 and the scores were graded as adequate and inadequate. A vein-viewer was used for studying cubital vein patterns (type 1-5). Phlebotomy outcome was defined based on need for re-puncture. Procedural outcomes in terms of target yield attained and RBC reinfusion completed. Chi square test and Mann- Whitney U test were used to assess the vein score and pattern against phlebotomy and procedural outcome. RESULTS: Out of 200 DDP collections, the phlebotomy was successful in 88 % with good procedural outcome in 94 % donations. The cut off in VAT scores for successful phlebotomy was ≥8 (AUC: 70 %). Median vein scores of the arm selected for phlebotomy was 9 and graded adequate in 154 (77 %) donations.Odds for successful phlebotomy was 3.7 times higher when donors had an adequate VAT grades(p = 0.003). Procedural outcomes was favourable when at least one arm had adequate VAT grade when compared to both arms being inadequate (98 % vs 82 %; p < 0.001). Phlebotomy failure was more with first time apheresis donors than repeat apheresis donors (p = 0.014). CONCLUSION: This study indicated that a VAT score with a cut off of ≥8 had better phlebotomy and procedural outcomes in DDP collections and that donor with at least one arm having the VAT score of ≥8 are preferred for DDP collections.
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Remoção de Componentes Sanguíneos/métodos , Plaquetas/citologia , Plaquetoferese/instrumentação , Plaquetoferese/métodos , Veias/anatomia & histologia , Veias/fisiologia , Adulto , Transfusão de Componentes Sanguíneos/instrumentação , Transfusão de Componentes Sanguíneos/métodos , Doadores de Sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Razão de Chances , Flebotomia , Estudos Prospectivos , Resultado do Tratamento , Adulto JovemRESUMO
INTRODUCTION: A 20 year review of health and health care presents the multiple challenges faced by South Africans. Health and poverty is highlighted with 45% of population living on approximately US$ 2 per day and 10 million living on less than US$ 1 per day. Widening disparities in health care provision between public and private sector hospital services exist. The South African population includes the largest number of people living with HIV infection/AIDS of any country in the world, with a 70% estimate of 7.5 million people living with HIV on antiretroviral therapy. The South African National Blood Service provides a mixed model therapeutic apheresis service including mobile service and fixed-site therapeutic apheresis and an apheresis collection of hematopoietic stem cell (HPC-A) service. Therapeutic apheresis modalities offered by SANBS include plasmapheresis, red cell exchange, leukocyte and platelet reduction. In addition, collection of plasma, thrombocytes, mononuclear cells including CD34+ cells (HPCs) and granulocytes by apheresis for plasma and cellular therapies, and customised apheresis products for research purposes is offered. An operational database for the period 2013 to 2020 was reviewed to characterise the SANBS's mixed therapeutic apheresis service and HPC-A service from 2013 to 2020 in terms of patient numbers, patient demographics, patient procedures, therapeutic apheresis indication or diagnosis, therapeutic apheresis modality, hospital service type, and the American Society for Apheresis (ASFA) category of diagnosis. METHODS: A retrospective review of therapeutic apheresis patients referred to SANBS characterising patient numbers, patient demographics, patient procedures, therapeutic apheresis indication or diagnosis, therapeutic apheresis modality (Linz, 2017), hospital service type, and the ASFA category of diagnosis (Padmanabhan et al., 2019) for the period 01 January 2013 to 31 December 2020 was completed. Data is obtained from a SANBS operational routinely utilised to record patient procedure data. Patient procedure data is manually recorded by apheresis nurses and indexed on to the operational database, with both processes audited. The review period is a convenience sample. Storage of the database and access of the operational database is in compliance with the Protection of Personal Information Act (Government Gazette, 2013). Therapeutic apheresis modalities analysed include Plasmapheresis, Red Cell Exchange, Leukopheresis, Thrombocytapheresis, Lymphocyte collection, Granulocyte collection, Haematopoietic stem cell collection by apheresis and customised apheresis products for research purposes. Customised apheresis products for research purposes is excluded from this review. Descriptive statistics is used. RESULTS: For the review period, 2,485 unique patients with 120 unique indications as recorded by referring clinicians received 13,518 procedures involving 7 therapeutic apheresis modalities at 78 hospitals (21 public sector and 57 private sector) and at 3 SANBS blood donor centres in 7 provinces of South Africa. The age range of patients serviced is 4 months to 90 years (medianâ¯=â¯39.5 years) (figure 1), 91% by procedure count was for patients 21 years of age or older, 62% were female, with 10,783 (79.6%) procedures performed in public sector hospitals. In all patients, the most common indications was plasmapheresis for thrombotic thromobocytopaenic purpura (52.5% of cumulative procedures), HPC-A for multiple myeloma (7.86%) and Antibody-mediated kidney transplant rejection (4.90%). Plasmapheresis was the most common therapeutic apheresis modality used (82.5% of cumulative procedures) followed by HPC-A (13.7%) and leukoreduction (3.39%). A range of indications for plasmapheresis (nâ¯=â¯65) and HPC-A (nâ¯=â¯41) were observed. Red cell exchange procedures was performed for patients with severe malaria and sickle cell disease indications. For leukoreduction indications, all patients were adults managed in public sector facilities and all were symptomatic. The most common indications were Chronic Myelogenous Leukemia, Chronic Lymphocytic Leukaemia and Multiple Myeloma. A pooled, total white cell count average of 457â¯×â¯109/L (range 141-689â¯×â¯109/L) prior to first procedure. Despite complex challenges for a national mixed model service, successful patient outcomes in emergent indications such as TTP (Louw et al., 2018; Swart et al., 2019) and engraftment post HPC-A in HSCT in multiple centres (Glatt, personal communication) are reported. CONCLUSION: The review confirms that apheresis medicine is increasingly used in South Africa in patients in both public and private sector, with the most common modalities being plasmapheresis, HPC-A and leukoreduction. Patients with HIV-associated TTP is the most commonly referred patient in both paediatric and adult patients and this is anticipated to continue. A growing HSCT transplant network capacity in South Africa is augmented through the mixed model mobile and fixed-site therapeutic apheresis services, including a mobile HPC-A service. The increasing number of HPC-A is a trend towards increasing numbers of patients support to HSCT for both adults and paediatric patients in private and public sector hospitals.
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Remoção de Componentes Sanguíneos/métodos , Unidades Móveis de Saúde/normas , Feminino , Humanos , Masculino , Estudos Retrospectivos , África do Sul , Fatores de TempoRESUMO
Familial hypercholesterolemia (FH) is an inherited disorder with retarded clearance of plasma LDL caused by mutations of the genes involved in the LDL receptor-mediated pathway and most of them exhibit autosomal dominant inheritance. Homozygotes of FH (HoFH) may have plasma LDL-C levels, which are at least twice as high as those of heterozygous FH (HeFH) and therefore four times higher than normal levels. Prevalence of HoFH had been estimated as 1 in 1,000,000 before but more recent genetic analysis surveys predict 1 in 170,000 to 300,000. Since LDL receptor activity is severely impaired, HoFH patients do not or very poorly respond to medications to enhance activity, such as statins, and have a poorer prognosis compared to HeFH. HoFH should therefore be clinically distinguished from HeFH. Thorough family studies and genetic analysis are recommended for their accurate diagnosis.Fatal cardiovascular complications could develop even in the first decade of life for HoFH, so aggressive lipid-lowering therapy should be initiated as early as possible. Direct removal of plasma LDL by lipoprotein apheresis has been the principal measure for these patients. However, this treatment alone may not achieve stable LDL-C target levels and combination with drugs should be considered. The lipid-lowering effects of statins and PCSK9 inhibitors substantially vary depending on the remaining LDL receptor activity of individual patients. On the other hand, the action an MTP inhibitor is independent of LDL receptor activity, and it is effective in most HoFH cases.This review summarizes the key clinical issues of HoFH as well as insurance coverage available under the Japanese public healthcare system.
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Remoção de Componentes Sanguíneos/métodos , Intervenção Médica Precoce , Hipercolesterolemia Familiar Homozigota , Proteínas Relacionadas a Receptor de LDL/genética , Reguladores do Metabolismo de Lipídeos , LDL-Colesterol/sangue , Intervenção Médica Precoce/métodos , Intervenção Médica Precoce/organização & administração , Fatores de Risco de Doenças Cardíacas , Hipercolesterolemia Familiar Homozigota/diagnóstico , Hipercolesterolemia Familiar Homozigota/tratamento farmacológico , Hipercolesterolemia Familiar Homozigota/epidemiologia , Hipercolesterolemia Familiar Homozigota/genética , Humanos , Cobertura do Seguro , Japão/epidemiologia , Reguladores do Metabolismo de Lipídeos/classificação , Reguladores do Metabolismo de Lipídeos/farmacologia , PrognósticoRESUMO
During autologous stem cell transplant, granulocyte colony-stimulating factors (G-CSF) serve the integral role of mobilizing hematopoietic cells into the peripheral blood for subsequent collection by leukapheresis. Filgrastim (Neupogen®) is a G-CSF and affects hematopoietic cells by stimulating growth and differentiation of neutrophils. Filgrastim-sndz (Zarxio®), a biosimilar of filgrastim, received landmark approval as the first biosimilar product approved by the FDA in the United States. As a result of the recent FDA approval, our medical center made the conversion in August 2016 from using filgrastim to filgrastim-sndz to provide patients the same benefits of the filgrastim injection at a reduced cost. This retrospective, observational cohort study evaluated the comparative efficacy of the filgrastim-sndz biosimilar in 147 patients who underwent mobilization prior to stem cell transplant with filgrastim between 1 August 2015 and 31 July 2016 or filgrastim-sndz between 1 September 2016 and 30 November 2017. The mean number of CD34 cells collected during apheresis was 7.38 × 106 in the filgrastim group and 8.86 × 106 in the filgrastim-sndz group. Filgrastim-sndz was significantly non-inferior, as the difference between filgrastim and filgrastim-sndz was -1.48 × 106 with an upper 95% confidence bound equal to -0.24 × 106 that did not include the non-inferiority margin of 1 × 106 (p = 0.0006). The median number of days of apheresis was 2 in both groups (p= 0.3273). In conclusion, the biosimilar product was non-inferior for mobilization and the conversion from filgrastim to filgrastim-sndz afforded patients similar efficacy for mobilization in stem cell transplant at a reduced cost.
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Medicamentos Biossimilares , Filgrastim/uso terapêutico , Mobilização de Células-Tronco Hematopoéticas/métodos , Transplante de Células-Tronco Hematopoéticas/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígenos CD34/imunologia , Remoção de Componentes Sanguíneos , Aprovação de Equipamentos , Feminino , Filgrastim/economia , Mobilização de Células-Tronco Hematopoéticas/economia , Transplante de Células-Tronco Hematopoéticas/economia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento , Estados Unidos , United States Food and Drug AdministrationRESUMO
INTRODUCTION: Severe familial hypercholesterolaemia (FH) causes premature disability and death due to atherosclerotic cardiovascular disease and is refractory to standard lipid-lowering therapies. Lipoprotein apheresis (LA) has long been a standard of care for patients with severe FH, but is invasive, expensive and time-consuming for patients and their caregivers. Newer drug therapies, including the proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors, may reduce the need for LA. MATERIALS AND METHODS: We audited the records of 16 patients (eight homozygous, eight heterozygous) treated with LA in Australia and New Zealand, 14 of whom subsequently commenced PCSK9 inhibitor therapy. LA was performed by cascade filtration in all centres. RESULTS: LDL-cholesterol was acutely lowered by 69 ± 7% in patients with homozygous FH and by 72 ± 9% in those with heterozygous FH, representing time-averaged reductions of 36 ± 12% and 34 ± 5%, respectively. LA was well-tolerated, and patients reported comparable quality of life to population and disease-related norms. After commencement of PCSK9 inhibitors, four of seven patients with homozygous FH had meaningful biochemical responses, with a reduction in the frequency of LA permitted in one patient and complete cessation in another. Four of seven patients with heterozygous FH were able to be managed without LA after commencing PCSK9 inhibitors. CONCLUSION: While PCSK9 inhibitors have reduced the need for LA, some patients with severe FH continue to require LA, and will require it for the foreseeable future. However, emerging therapies, including angiopoetin-like 3 inhibitors, may further reduce the need for LA.
Assuntos
Remoção de Componentes Sanguíneos/métodos , LDL-Colesterol/sangue , Hiperlipoproteinemia Tipo II/terapia , Inibidores de PCSK9 , Adolescente , Adulto , Remoção de Componentes Sanguíneos/efeitos adversos , Remoção de Componentes Sanguíneos/economia , Terapia Combinada , Feminino , Custos de Cuidados de Saúde , Humanos , Hiperlipoproteinemia Tipo II/sangue , Hiperlipoproteinemia Tipo II/psicologia , Masculino , Qualidade de Vida , Adulto JovemRESUMO
BACKGROUND: Numerous conditions are responsive to therapeutic apheresis (TA) and cellular therapy (CT) treatments. Both TA and CT are two broad and diverse knowledge fields within transfusion medicine (TM). We therefore sought to survey all the TM fellowship program directors (PDs) in the United States to examine the current fellow state education in TA and CT. METHODS: A 37-question survey was sent to all PDs to collect details of TA and CT training for TM fellows. RESULTS: Responses from 29/51 (56.9%) surveyed programs were received. Most PDs considered TA and CT training for their fellows more than adequate. Two PDs from programs that did not directly oversee TA and CT services at their training sites stated that their program's training in these two areas were only "slightly adequate" or "moderately inadequate." Detailed analysis of training in TA, cell collection, and CT suggests that trainees from programs with direct oversight of these services had longer training and more learning experiences compared to those in which outside rotations were required. CONCLUSIONS: Transfusion medicine fellowship training in TA and CT varies. Most respondents, and particularly those from programs directly overseeing TA services, reported their fellows were adequately prepared in TA. Cellular therapy collections and laboratory operations, however, are less consistent areas of training despite the rapid expansion of these fields. Our survey suggests that a greater emphasis in CT training is needed.
Assuntos
Remoção de Componentes Sanguíneos/métodos , Terapia Baseada em Transplante de Células e Tecidos , Bolsas de Estudo , Medicina Transfusional/educação , Células-Tronco Hematopoéticas/citologia , HumanosRESUMO
BACKGROUND: The majority of blood transfusion safety strategies recommended by the WHO for resource-poor countries focus mainly on reducing the risk of transfusion-transmitted infections (TTIs). Other technologies such as leucocyte reduction may represent complementary strategies for improving transfusion safety. OBJECTIVE: To evaluate the role of using leucocyte reduced blood in a resource-poor country. METHODS: Pre-storage leucocyte reduced (LR) red blood cells (RBCs) were specially prepared for the Tissue Oxygenation by Transfusion in severe Anaemia and Lactic acidosis (TOTAL) study, at the Uganda Blood Transfusion Services from February 2013 through May 2015. Quality control tests were performed to evaluate the procedure, and the incremental cost of an LR-RBC unit was estimated. RESULTS: A total of 608 RBCs units were leucocyte reduced. Quality control tests were performed on 55 random RBCs units. The median (IQR) residual leucocyte count was 4 (0·5-10) WBC/uL, equivalent to 1·8x106 WBC per unit. The estimated incremental unit cost of leucocyte reduction was $37 USD per LR RBC unit. CONCLUSION: Leucocyte reduction of blood in a resource-poor country is doable although relatively costly. As such, its value in resource-poor countries should be weighed against other transfusion safety propositions.
Assuntos
Transfusão de Sangue/normas , Procedimentos de Redução de Leucócitos , Leucócitos , Segurança , Reação Transfusional/prevenção & controle , Acidose Láctica/terapia , Anemia/terapia , Remoção de Componentes Sanguíneos , Filtração , Humanos , Contagem de Leucócitos , Procedimentos de Redução de Leucócitos/economia , Procedimentos de Redução de Leucócitos/métodos , UgandaRESUMO
The aim of this paper was to explain the insurance coverage status of therapeutic apheresis (excluding CHDF) in Japan, alongside the social system of medical reimbursement and concerns regarding the future sustainability of the healthcare system. Insurance schemes and premiums differed for individuals at different levels in the society (eg, municipal residents, employees, and public servants). Insurance premiums and their rates varied depending on the total household income, the number of people living together, age, and the place of residence. In addition, the medical expense subsidies for children through public expenditure were also described. Japan's generous insurance system and multiple medical expense subsidies provide financial support for patients. With Japan's history of medical expense subsidies based on the policy of supporting intractable diseases, we have established an environment where all citizens can receive therapeutic apheresis when needed if they are affected by a disease for which insurance coverage is indicated.
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Remoção de Componentes Sanguíneos/economia , Remoção de Componentes Sanguíneos/instrumentação , Reembolso de Seguro de Saúde/economia , Gastos em Saúde , Humanos , JapãoRESUMO
Indications for therapeutic and donor apheresis continue to increase and expand into new domains of therapy. The level and amount of apheresis education in residency programs remains heterogeneous, which may translate into varying degrees of clinical confidence in providing care. The purpose of this study was to assess Canadian clinicians' perceptions of their apheresis training in order to help demonstrate a need for a concrete apheresis education in residency curricula. A 22-question survey was distributed to Canadian graduates who recently completed training (2013-2017) in the following specialties: hematology, nephrology, transfusion medicine, and hematologic pathology. Questions regarding clinician perception of their training were asked using a Likert scale. Fifty-seven survey responses (32% response rate) were obtained from recent graduates from hematology (29/57, 51%), nephrology (21/57, 37%), hematologic pathology (4/57, 7%) and transfusion medicine (3/57, 5%). Although most respondents (68%) received some form of apheresis exposure during residency, only 23% reported a formal apheresis rotation. Only 40% felt that the amount of time devoted to apheresis education was sufficient, and only four respondents (7%) felt confident providing independent apheresis care at the end of training. Overall, these findings suggest that a common, dedicated apheresis curriculum in these training programs could possibly increase knowledge and competence of trainees, and provide a more solid foundation in apheresis for future practice.
Assuntos
Remoção de Componentes Sanguíneos/métodos , Internato e Residência/métodos , Avaliação das Necessidades/estatística & dados numéricos , Canadá , Humanos , Inquéritos e QuestionáriosRESUMO
Without cellular blood products such as platelet concentrates (PC), red blood cell concentrates (RCC), and hematopoietic stem cells (HPSC) modern treatments in medicine would not be possible. An unresolved challenge is the assessment of their quality with minimal cell manipulation. Minor changes in production, storage conditions, or blood bag composition may impact cell function, which can have important consequences on product integrity. This is especially relevant for personalized medicine, such as autologous T-cell therapy. Today a robust methodology that globally determines cell status directly before transfusion or transplantation is lacking. We demonstrate that measuring viscoelastic characteristics of peripheral blood cells using real-time deformability cytometry (RT-DC) provides comprehensive information on product quality, which is not accessible using conventional quality control tests. In addition, RT-DC requires few cells, a minimal sample volume and has a rapid turnaround time. We compared RT-DC to standard in vitro quality assays assessing: i) PC after storage at 4 °C and room temperature; ii) magnetic nanoparticle labeled platelets; iii) RCC stored in blood bags with different plasticizers; iv) RCC after gamma irradiation; and v) HPSC after cryopreservation with 5% or 10% dimethyl sulfoxide, respectively. Additionally, we evaluated the engraftment time of patients' platelets and leukocytes after transplantation of HPSC products. Our results demonstrate that label-free mechano-phenotyping can be used as a potential biomarker for quality assessment of cell-based pharmaceutical products.