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Transfusion Therapy (transfusion + therapy)
Selected AbstractsPrevention of red cell alloimmunization by CD25 regulatory T cells in mouse modelsAMERICAN JOURNAL OF HEMATOLOGY, Issue 8 2007Jin Yu Transfusion therapy is currently an effective therapeutic intervention in a number of diseases, including sickle cell disease. However, its use is complicated by a high incidence of red blood cell (RBC) alloimmunization in the transfusion recipients. The identification of T regulatory cells (Tregs) among the CD4+ CD25+ T cell subset as key regulators of peripheral tolerance in mice as well as humans has opened an exciting era in the prevention and treatment of autoimmune disease and for improving organ transplantation. However, their potential in inducing transfusion tolerance remains to be explored. We used red cells from mice transgenic for human glycophorin A blood group antigen as donor cells and transfused wild-type mice to induce alloantibodies, as an experimental system to study RBC alloimmunization. We found that depletion with anti-CD25 enhanced the alloantibody production, indicating that CD25 Tregs play an important role in regulation of alloantibody responses. More importantly, adoptive transfer of purified population of CD4+CD25+ but not CD4+CD25, cells from naïve mice prevented the induction of IgG and IgM alloantibody production in transfusion recipients, with a concomitant reduction in activated splenic B cells and macrophages. Similarly, adoptive transfer of purified populations of CD4+CD25+ cells from naïve mice into naïve syngeneic recipients inhibited the anti-Ig response to rat RBCs in the recipients but transfer of control CD4+CD25, cells did not. Altogether, our results demonstrate that Tregs participate in the control of transfusion-associated RBC alloantibody responses, opening up the possibility that Treg immunotherapy may be exploited for suppressing transfusion immunization events. Am. J. Hematol., 2007. © 2007 Wiley-Liss, Inc. [source] Distribution and frequency of , -thalassemia mutations in northwestern and central GreeceEUROPEAN JOURNAL OF HAEMATOLOGY, Issue 2 2003I. Georgiou Abstract: Objectives : , -Thalassemia is a common autosomal recessive disorder resulting from over 200 different mutations of the , -globin genes. The spectrum of , -thalassemia mutations in Greece has been previously described in the population of the capital city of Athens, or in , -thalassemia patients having transfusion therapy. The aim of the present study was to identify the distribution of the most common , -thalassemia mutations in the population of northwestern and central Greece. Methods : The data for this study were derived from a total of 1130 unrelated subjects including 46 , -thalassemia major, three , -thalassemia intermedia and 1081 carriers identified in our antenatal screening program. , -Thalassemia mutations were identified by ARMS, DGGE and Reverse Dot Blot. Results : The most common mutation, IVS-I-110, is followed, in order of frequency, by the mutations Cd-39, IVS-I-1, IVS-II-1, Cd-6, IVS-I-6, IVS-I-5, IVS-II-745, Cd-5 and 44 bp del. IVS-I-110 and Cd-39 frequencies are similar with those found in other Balkan countries. Significant differences in regional distribution were observed. The results showed a clear drift of the distribution of the most frequent IVS-I-110 mutation in the south,north (29.4, 40.0, 44.6 and 61.7%) and the east,west axis (31.8 and 44.6%). Conclusions : Population screening and prenatal diagnosis are significantly facilitated by these data. Furthermore, the detailed distribution tables of , -thalassemia mutations are essential for counseling and extraction of genetic diversity estimates for population genetic studies in other inherited disorders. [source] Optimal timing and dosing of platelet transfusionsISBT SCIENCE SERIES: THE INTERNATIONAL JOURNAL OF INTRACELLULAR TRANSPORT, Issue n1 2010N. M. Heddle Background, Over the past 20 years there have been more than 20 randomized controlled trials (RCTs) that have investigated various aspects of platelet transfusion therapy in haematology/oncology patients. These studies have focused on the best platelet product, the importance of ABO compatibility, pathogen inactivation of platelets, platelet triggers and the optimal platelet dose. Aims, This article summarizes current evidence to support the timing and dosing of platelet transfusions and to explore some ideas of where clinical research in this area may be heading. Materials and Methods, The articles reviewed in this presentation were identified through a search of PubMed using the term, platelet transfusion and setting limits to identify clinical studies, human studies and manuscripts in English. Results and Discussion, Three RCTs have informed practices around platelet transfusion trigger with the largest study by Rebulla et al., being the primary study that has changed practices worldwide, with a move towards a lower prophylactic platelet transfusion trigger of 10 × 109/l. Two groups (Germany and Oxford, UK) are currently investigating whether we can push the boundaries of prophylactic platelet transfusions even further by eliminating this form of therapy. Preliminary results from these studies have been published but we will await the final results to determine whether this research will indeed change practice. Over the past year there has also been two major studies (one by the BEST Collaborative, and the second by the US Transfusion Medicine/Hemostasis Network), that provide new information to guide platelet dosing. The Study by the BEST Collaborative (SToP) compared low dose platelets to standard dose platelets with WHO bleeding greater than or equal to Grade 2 as the primary outcome. The US study (PLADO) compared three doses (low, medium and high) and measured the same outcome (WHO bleeding , Grade 2). Conclusions, Although all of these studies further our knowledge to prescribe platelet transfusions, they also raise some interesting questions about the clinical relevance of the outcomes that we are currently using for these studies. The trend over the past decade has been to use bleeding as the primary outcome; however, bleeding is a complex composite outcome (Grades 2, 3 and 4) comprised of some surrogate components (Grades 2 and 3). It is also an outcome that may be difficult to measure and grade in a consistent and reliable manner. The clinical relevance of this outcome is also complex and may vary depending on the perspective from which it is viewed. [source] Granulocyte transfusion therapy in abdominal organ transplant recipientsJOURNAL OF CLINICAL APHERESIS, Issue 5 2009Nikhil R. Oak Abstract Background: Patients with neutropenia are at increased risk for infections. Granulocyte transfusions (GT) have had mixed success in treatment of neutropenic infections in adult patients with hematologic malignancy. This study examined the outcomes of GT therapy in neutropenic solid organ transplant recipients, a novel population for this therapy. Methods: We performed a retrospective examination of the transfusion and medical records of all 14 solid organ-transplant recipients without hematologic malignancy who experienced neutropenia and received GT therapy from 2004 to 2006. Results: Twelve patients received GT therapy for an active infection and two patients for infection prophylaxis. The mean absolute neutrophil count (ANC) one day increment per GT in these patients was 526/,l (median 215/,l). The mean ANC one day increment per dose of 1010 granulocytes was 246/,l (median 86/,l). Of the 12 infected patients, four patients (33%) showed a clinical response to GT with improvement or resolution of the infection, 7 (58%) patients had no clinical response and one additional patient had a clinical response to a course of GT but died during a second GT course. Neither patient receiving GT for prophylaxis developed an infection. Conclusions: We observed temporal increases in ANC to levels above 1,000/,l in 15/18 (83.3%) courses of GT. We observed a clinical response to infection in 5/12 (42%) patients, the remaining infected patients had no clinical response. Our results suggest that GT therapy in neutropenic solid organ transplant recipients can boost peripheral blood neutrophil counts. Additional studies areneeded to document an independent clinical benefit for GT in this patient population. J. Clin. Apheresis, 2009. © 2009 Wiley-Liss, Inc. [source] Controversies related to red blood cell transfusion in critically ill patientsJOURNAL OF VETERINARY EMERGENCY AND CRITICAL CARE, Issue 2 2010DACVECC, DACVIM, Jennifer E. Prittie DVM Abstract Objective , To review the evolution of and controversies associated with allogenic blood transfusion in critically ill patients. Data sources , Veterinary and human literature review. Human Data Synthesis , RBC transfusion practices for ICU patients have come under scrutiny in the last 2 decades. Human trials have demonstrated relative tolerance to severe, euvolemic anemia and a significant outcome advantage following implementation of more restricted transfusion therapy. Investigators question the ability of RBCs stored longer than 2 weeks to improve tissue oxygenation, and theorize that both age and proinflammatory or immunomodulating effects of transfused cells may limit efficacy and contribute to increased patient morbidity and mortality. Also controversial is the ability of pre- and post-storage leukoreduction of RBCs to mitigate adverse transfusion-related events. Veterinary Data Synthesis , While there are several studies evaluating the transfusion trigger, the RBC storage lesion and transfusion-related immunomodulation in experimental animal models, there is little research pertaining to clinical veterinary patients. Conclusions , RBC transfusion is unequivocally indicated for treatment of anemic hypoxia. However, critical hemoglobin or Hct below which all critically ill patients require transfusion has not been established and there are inherent risks associated with allogenic blood transfusion. Clinical trials designed to evaluate the effects of RBC age and leukoreduction on veterinary patient outcome are warranted. Implementation of evidence-based transfusion guidelines and consideration of alternatives to allogenic blood transfusion are advisable. [source] Blood loss during posterior spinal fusion surgery in patients with neuromuscular disease: is there an increased risk?PEDIATRIC ANESTHESIA, Issue 9 2003Alice Edler MD, MA (EDUC) Summary Background Scoliosis surgery in paediatric patients can carry significant morbidity associated with intraoperative blood loss and the resultant transfusion therapy. Patients with neuromuscular disease may be at an increased risk for this intraoperative blood loss, but it is unclear if this is because of direct vascular pathophysiological changes or the fact that neuromuscular patients typically have more extensive orthopaedic disease and more vertebral segments involved. This study examined the risk of extensive blood loss (>50% of total blood volume) in patients with neuromuscular disease compared with patients who did not have neuromuscular disease when the extent of the surgery (number of segments fused), age and preoperative coagulation profile where taken into consideration. Methods Retrospective chart review of 163 paediatric patients was preformed. Patients who carried a diagnosis of preexisting neuromuscular disease were classified as such. Idiopathic, traumatic and iatrogenic scoliosis were classified as nonneuromuscular. Extensive blood loss was defined as >50% of estimated total blood volume. Logistic regression was used to predict the risk of extensive blood loss between the two groups when age, weight, extent of surgery was controlled for and anaesthetic and surgical techniques remained similar. Results Patients with neuromuscular disease did not vary significantly in age, weight, or preoperative haematocrit and platelet count from patients without neuromuscular disease. Neuromuscular patients did have significantly more vertebral segments fused. When this difference was controlled for statistically, neuromuscular patients had an almost seven times higher risk (adjusted odds ration 6.9, P < 0.05) of losing >50% of their estimated total blood volume during scoliosis surgery. Conclusions Patients with neuromuscular disease can present various anaesthetic challenges during scoliosis surgery, among these is the inherent risk of extensive blood loss. Recognizing this may help anaesthesiologists and surgeons more accurately prepare for and treat intraoperative blood loss during scoliosis surgery in patients with neuromuscular disease. [source] Microarray analysis of liver gene expression in iron overloaded patients with sickle cell anemia and beta-thalassemia,AMERICAN JOURNAL OF HEMATOLOGY, Issue 6 2009Jonathan M. Flanagan Chronic transfusion therapy is used clinically to supply healthy erythrocytes for patients with sickle cell anemia (SCA) or beta-thalassemia major (TM). Despite the benefits of red blood cell transfusions, chronic transfusions lead to iron accumulation in key tissues such as the heart, liver, and endocrine glands. Transfusion-acquired iron overload is recognized as a cause of morbidity and mortality among patients receiving chronic transfusions. At present, there is little understanding of molecular events that occur during transfusional iron loading and the reasons for the large inter-individual variation observed clinically in transfusion-acquired iron accumulation. To address these issues, we examined whether any liver-expressed genes in SCA or TM patients with transfusional iron overload were associated with the degree of iron accumulation. Specifically, we performed microarray analysis on liver biopsy specimens comparing SCA patients with mild or severe iron overload and also compared SCA with TM patients. Fifteen candidate genes were identified with significantly differential expression between the high and low liver iron concentrations. SCA patients and 20 candidate genes were detected between the SCA and TM patient comparison. Subsequent quantitative PCR experiments validated 12 candidate genes; with GSTM1, eIF5a, SULF2, NTS, and HO-1 being particularly good prospects as genes that might affect the degree of iron accumulation. Future work will determine the baseline expression of these genes prior to transfusional iron overload and elucidate the full impact of these genes on the inter-individual variation observed clinically in transfusion-acquired iron accumulation. Am. J. Hematol. 2009. © 2009 Wiley-Liss, Inc. [source] Increased prevalence of iron-overload associated endocrinopathy in thalassaemia versus sickle-cell diseaseBRITISH JOURNAL OF HAEMATOLOGY, Issue 4 2006Ellen B. Fung Summary Iron-overload associated endocrinopathy is the most frequently reported complication of chronic transfusion therapy in patients with thalassaemia (Thal). This study compared iron-overloaded subjects with Thal (n = 142; 54%M; age 25·8 ± 8·1 years) and transfused sickle-cell disease (Tx-SCD; n = 199; 43%M, 24·9 ± 13·2 years) to non-transfused SCD subjects (non-Tx-SCD; n = 64, 50%M, 25·3 ± 11·3 years), to explore whether the underlying haemoglobinopathy influences the development of endocrinopathy. Subjects were recruited from 31 centres in the USA, Canada and the UK. Subjects with Thal had more evidence of diabetes (13% vs. 2%, P < 0·001), hypogonadism (40% vs. 4%, P < 0·001), hypothyroidism (10% vs. 2%, P = <0·001) and growth failure (33% vs. 7%, P < 0·001), versus Tx-SCD. Fifty-six per cent of Thal had more than one endocrinopathy compared with only 13% of Tx-SCD (P < 0·001). In contrast, Tx-SCD was not different from non-Tx-SCD. Multivariate analysis indicated that endocrinopathy was more likely in Thal than SCD [Odds Ratio (OR) = 9·4, P < 0·001], with duration of chronic transfusion a significant predictor (OR = 1·4 per 10 years of transfusion, P = 0·04). Despite iron overload, endocrinopathy was not increased in Tx-SCD versus non-Tx-SCD, suggesting that the underlying disease may modulate iron-related endocrine injury. However, because transfusion duration remained a significant predictor of endocrinopathy, these data should be confirmed in SCD subjects that have been chronically transfused for longer periods of time. [source] | ||||||||||