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Hemostatic abnormalities and thrombotic risk associated with coronavirus disease 2019 (COVID-19) are among the most discussed topics in the management of this disease. The aim of this position paper is to provide the opinion of Brazilian experts on the thromboprophylaxis and management of thrombotic events in patients with suspected COVID-19, in the sphere of healthcare in Brazil. To do so, the Brazilian Society of Thrombosis and Hemostasis (BSTH) and the Thrombosis and Hemostasis Committee of the Brazilian Association of Hematology, Hemotherapy and Cellular Therapy (ABHH) have constituted a panel of experts to carefully review and discuss the available evidence about this topic. The data discussed in this document was reviewed by May 9, 2020. Recommendations and suggestions reflect the opinion of the panel and should be reviewed periodically as new evidence emerges.

Autoimmune diseases are an important field for the development of bone marrow transplantation, or hematopoietic stem cell transplantation. In Europe alone, almost 3000 procedures have been registered so far. The Brazilian Society for Bone Marrow Transplantation (Sociedade Brasileira de Transplantes de Medula Óssea) organized consensus meetings for the Autoimmune Diseases Group, to review the available literature on hematopoietic stem cell transplantation for autoimmune diseases, aiming to gather data that support the procedure for these patients. Three autoimmune diseases for which there are evidence-based indications for hematopoietic stem cell transplantation are multiple sclerosis, systemic sclerosis and Crohn's disease. The professional stem cell transplant societies in America, Europe and Brazil (Sociedade Brasileira de Transplantes de Medula Óssea) currently consider hematopoietic stem cell transplantation as a therapeutic modality for these three autoimmune diseases. This article reviews the evidence available.

Background Mantle cell lymphoma (MCL) is a B cell malignancy that can be aggressive and with a poor prognosis; the clinical course is heterogeneous. The epidemiology of MCL in Asia is not well documented but appears to comprise 2–6% of all lymphoma cases based on available data, with variation observed between countries. Although international guidelines are available for the treatment of MCL, there is a lack of published data or guidance on the clinical characteristics and management of MCL in patient populations from Asia. This paper aims to review the available treatment and, where clinical gaps exist, provide expert consensus from the Asian Lymphoma Study Group (ALSG) on appropriate MCL management in Asia. Body Management strategies for MCL are patient- and disease stage-specific and aim to achieve balance between efficacy outcomes and toxicity. For asymptomatic patients with clearly indolent disease, observation may be an appropriate strategy. For stage I/II disease, following international guidelines is appropriate, which include either a short course of conventional chemotherapy followed by consolidated radiotherapy, less aggressive chemotherapy regimens, or a combination of these approaches. For advanced disease, the approach is based on the age and fitness of the patient. For young, fit patients, the current practice for induction therapy differs across Asia, with cytarabine having an important role in this setting. Hematopoietic stem cell transplantation (HSCT) may be justified in selected patients because of the high relapse risk. In elderly patients, specific chemoimmunotherapy regimens available in each country/region are a treatment option. For maintenance therapy after first-line treatment, the choice of approach should be individualized, with cost being an important consideration within Asia. For relapsed/refractory disease, ibrutinib should be considered as well as other follow-on compounds, if available. Conclusion Asian patient-specific data for the treatment of MCL are lacking, and the availability of treatment options differs between country/region within Asia. Therefore, there is no clear one-size-fits-all approach and further investigation on the most appropriate sequence of treatment that should be considered for this heterogeneous disease.

BCR-ABL1 kinase domain (KD) mutation status is considered to be an important element of clinical decision algorithms for chronic myeloid leukemia (CML) patients who do not achieve an optimal response to tyrosine kinase inhibitors (TKIs). Conventional Sanger sequencing is the method currently recommended to test BCR-ABL1 KD mutations. However, Sanger sequencing has limited sensitivity and cannot always discriminate between polyclonal and compound mutations. The use of next-generation sequencing (NGS) is increasingly widespread in diagnostic laboratories and represents an attractive alternative. Currently available data on the clinical impact of NGS-based mutational testing in CML patients do not allow recommendations with a high grade of evidence to be prepared. This article reports the results of a group discussion among an ad hoc expert panel with the objective of producing recommendations on the appropriateness of clinical decisions about the indication for NGS, the performance characteristics of NGS platforms, and the therapeutic changes that could be applied based on the use of NGS in CML. Overall, these recommendations might be employed to inform clinicians about the practical use of NGS in CML.

BACKGROUND and Objective: β thalassemia major is a severe disease with high morbidity . The world prevalence of carriers is around 1.5–7%. The aim of the present study was to find a reliable formula for detecting β thalassemia carriers using a large database of more than 22,000 samples obtained from a homogeneous population of childbearing age women with 14% of β thalassemia carriers and to check previously published formulas. METHODS: We applied a mathematical method based on the support vector machine (SVM) algorithm in the search for a reliable formula that can differentiate between thalassemia carriers and non-carriers, including normal counts or counts suspected to belong to iron-deficient women. RESULTS: Shine's formula and ours showed >98% sensitivity and >99.77% NPV. All other published formulas gave inferior results. CONCLUSIONS: We found a reliable formula that can be incorporated into any automatic blood counter to alert health providers to the possibility of a woman being a β thalassemia carrier. A further simple hemoglobin characterization by HPLC analysis should be performed to confirm the diagnosis, and subsequent family studies should be carried out. Our SVM formula is currently limited to women of fertility age until further analysis in other groups can be performed.

COMMENT TO THE PAPER "PREVENTION OF BETA-THALASSEMIA IN NORTHERN ISRAEL - A COST-BENEFIT ANALYSIS” BY KOREN ET AL

With survival expectation that of age-matched controls and given excellent response and worldwide access to tyrosine kinase inhibitors (TKI), family planning is increasingly important for a considerable fraction of patients with chronic myeloid leukemia (CML). The potential for therapy discontinuation (“treatment free remission”) can afford the opportunity for a CML patient in deep response to plan and carry a pregnancy to full term without any therapeutic interventions. However, the reality of pregnancy desired or occurring when patients are not eligible for treatment-free remission raises the discussion of therapy choices during pregnancy. To date there are no official guidelines available to assist patients and clinicians with these decisions. This first position paper aims to analyze information published and presented surrounding this challenging area, with focus on different scenarios of disease burden and time from CML diagnosis, including CML discovered during pregnancy and pregnancy during CML treatment. An updated review, supported by data and presented together with authors’ joint recommendations, is aimed to counsel the practical management of CML patients and pregnancy.

Background: Alloimmunization is an immune response against foreign antigens which introduced into the body through transfusion, pregnancy, or transplantation. This phenomenon is a big challenge in patients, which require regular transfusions. In the current study, we tried to have a comprehensive review on the status of alloimmunization in Iran. For this purpose, we searched for papers investigating alloimmunization in transfusion-dependent patients and also in patients with no regular transfusions who are candidate for surgery or who need blood. Methods: We searched PubMed, Google Scholar, SID, and MAGIRAN databases using the following keywords: “blood transfusion,” “alloimmunization,” “alloantibodies,” “irregular antibodies,” “red cell antibodies,” and “Iran.” No limitation for the date of publication and language of the papers was defined. All the identified records were then screened for the relevance and duplication. Results: A total of 22 papers were included in this study. All of the studies were conducted from 1999 to 2016 and providing alloimmunization data from different cities all over of Iran. In general, the results showed that the most prevalent alloantibodies are anti-Kell (anti-K antigen) and anti-Rh system, mainly anti-E, anti-D, anti-C, and anti-c. Conclusion: Anti-Kell and anti-Rh antibodies are the most prevalent antibodies responsible for alloimmunization in Iranian population.

Kassie A, Birara S. J Blood Med. 2020;11:525–532. The Editor-in-Chief and Publisher of the Journal of BloodMedicine wish to retract the published article. It has come to our attention that a very similar version ofthis article was also published in PLOS ONE, Mar 2, 2020.https://doi.org/10.1371/journal.pone.0228929. The authorsfailed to properly attribute the source of their previouspublication or disclose this to the editor. Thus, it hasbeen deemed to be a redundant publication and the editorhas requested for the paper to be retracted. Our decision-making was informed by our policy on publishingethics and integrity and the COPE guidelines onretraction. The retracted article will remain online to maintain thescholarly record, but it will be digitally watermarked oneach page as “Retracted”. This retraction relates to this paper

The division of CLL into 2 broad subsets with highly significant differences in clinical behavior was reported in 2 landmark papers in Blood in 1999.1,2 The simple analysis of the mutational status of the IGV regions provided both a prognostic indicator and an insight into the cellular origins. Derivation from B cells with very low or no IGV mutations generally leads to a more aggressive disease course than derivation from B cells with higher levels. This finding focused attention on surface Ig (sIg), the major B-cell receptor, and revealed dynamic antigen engagement in vivo as a tumor driver. It has also led to new drugs aimed at components of the intracellular activation cascades. After 20 years, the 2 senior authors of those papers have looked at the history of the observations and at the increasing understanding of the role of sIg in CLL that have emanated from them. As in the past, studies of CLL have provided a link between biology and the clinic, enabling more precise targeting which attacks critical pathways but minimizes side effects.

Minimal residual disease is the most powerful predictor of outcome in acute leukemia and is useful in therapeutic stratification for acute lymphoblastic leukemia protocols. Nowadays, the most reliable methods for studying minimal residual disease in acute lymphoblastic leukemia are multiparametric flow cytometry and polymerase chain reaction. Both provide similar results at a minimal residual disease level of 0.01% of normal cells, that is, detection of one leukemic cell in up to 10,000 normal nucleated cells. Currently, therapeutic protocols establish the minimal residual disease threshold value at the most informative time points according to the appropriate methodology employed. The expertise of the laboratory in a cancer center or a cooperative group could be the most important factor in determining which method should be used. In Brazil, multiparametric flow cytometry laboratories are available in most leukemia treatment centers, but multiparametric flow cytometry processes must be standardized for minimal residual disease investigations in order to offer reliable and reproducible results that ensure quality in the clinical application of the method. The Minimal Residual Disease Working Group of the Brazilian Society of Bone Marrow Transplantation (SBTMO) was created with that aim. This paper presents recommendations for the detection of minimal residual disease in acute lymphoblastic leukemia based on the literature and expertise of the laboratories who participated in this consensus, including pre-analytical and analytical methods. This paper also recommends that both multiparametric flow cytometry and polymerase chain reaction are complementary methods, and so more laboratories with expertise in immunoglobulin/T cell receptor (Ig/TCR) gene assays are necessary in Brazil.

Guy Young,1 Caitlyn T Solem,2,3 Kate Hoffman,4 Jenna Kabawat,4 A Simon Pickard,3 Robert Z Gut,5 David L Cooper51Children's Center for Cancer and Blood Disorders, Children's Hospital Los Angeles, Los Angeles, CA, 2Pharmerit, Bethesda, MD, 3Center for Pharmacoeconomic Research, University of Illinois at Chicago, Chicago, IL, 4Outcome Sciences, Cambridge, MA, 5Novo Nordisk Inc, Princeton, NJ, USAObjective: The daily recordings of treatment by patients with congenital hemophilia with inhibitors and their caregivers were assessed as part of the Dosing Observational Study in Hemophilia (DOSE) to understand the patterns of bypassing agent use and health-related quality of life.Methods: Frequently bleeding patients prescribed recombinant activated factor VII as first-line therapy were eligible. Participants recorded daily paper diaries for at least 90 days and until at least four bleeding episodes had occurred. Web-based entry was optional. Assessment included bleeding status, work or school day status, bleeding episode, treatment, impact on planned activities, and health-related quality of life.Results: Diaries were completed by 18 adults and 19 caregivers (21 children). A total of 4063 diary days and 194 bleeding episodes over 491 bleed days were recorded. A small proportion of diary days were bleed days (8.2%) or treatment days (8.2%). Half the bleed days were not planned work or school days for patients (53%) or caregivers (48%). An exact agreement was observed between electronic and paper records for 93% of the reviewed health-related quality of life measurements.Conclusion: Daily diary completion by patients and caregivers is feasible and provides insight into the impact of congenital hemophilia with inhibitors on daily activities and overall quality of life. Positive participation and completion rates were supported by frequent patient contact made by independent patient support liaison personnel.Keywords: daily assessment, recombinant activated factor VII, rFVIIa, NovoSeven, quality of life

In this issue of the Revista Brasileira de Hematologia e Hemoterapia, Ferreira et al. present a study entitled "Clinical and functional evaluation of the joint status of hemophiliac adults at a Brazilian blood center"(1). The authors are to be commended for presenting their paper on the outcomes of the clinical and functional evaluation of adults with hemophilia from a Hemophilia Centre in Brazil. The findings identify the importance of evaluating this specific group of patients with hemophilia in order to develop a deep understanding of their physical status and the problems that this can pose for the individuals concerned. The findings will also provide evidence to begin to address the issues raised in the study and it is hoped that this will ultimately improve patient outcomes. The use of standardized measures is essential in this regard and the authors have used two well established tools to assess the adults in the study. This scientific comment will make three observations on the findings outlined in the paper - The importance of primary prophylaxis - The use of standardized measures - The lack of engagement with physiotherapy

Beta-thalassemia is considered one of the most common genetic disorders which mass migration is introducing to countries worldwide and challenging them with its management. Advanced and improved medical care has allowed us to prolong the lives of thalassemia patients, simultaneously uncovering novel complications and outlining new challenges. We herein present in this special issue of Anemia some of the most cutting-edge research outcomes pertaining to the latest complications and the novel treatment strategies in iron-chelation therapy. We also study the effects of these interventions on the quality of life of patients. It is studies like these that serve as the basis of evidence-based medicine and guide clinicians through their process of decision making. One article of this special issue addresses the new method of using transactional Doppler ultrasonography for measuring intracranial blood flow velocity in patients with beta-thalassemia intermedia. This study shows higher blood flow velocity in these patients compared to the control group, which may point to a higher risk of ischemic events in the future. Another paper discusses that thalassemic DNA-containing red blood cells are under oxidative stress, which induces externalization of phosphatidylserine. This mechanism is involved in the removal of these cells from the circulation by the spleen, similar to that of the removal of senescent red blood cells. This special issue also includes a paper explaining the pathophysiology of bone modifications in beta-thalassemia. Imbalance in mineral turnover resulting in abnormal regulation of bone metabolism may be related to hormonal and genetic factors, iron overload, and iron chelation therapy. These factors and their contribution are addressed. Moreover, a review article that addresses the mechanism of tissue damage arising from iron overload in patients with β-thalassemia major is presented. It is the result of oxidative stress from free radical production, altered antioxidant enzymes, and its interaction with other essential trace element levels. The last paper presented is a study comparing the quality of life in patients with β-thalassemia major and myelodysplastic syndrome with iron-overload treated either with deferasirox or deferoxamine injections. The results show that deferasirox can improve health-related quality of life treatment satisfaction and adherence compared to subcutaneous deferoxamine injection. This issue is crucial and often neglected in the long-term treatment of patients with iron overload. Mehran Karimi Sezaneh Haghpanah Ali T. Taher Maria Domenica Cappellini

Eighty-five years ago Dr. Guido Fanconi described a family with three brothers with microcephaly, hyperpigmentation of the skin, hypoplasia of the testes, and who developed a lethal anemia between the ages of 5 and 7 [1, 2]. Since 1931, patients with this distinctive combination of clinical features have been classified as having Fanconi anemia (FA). To date, diagnosis of this disease, which as we know can manifest with variable clinical presentation, is based on increased chromosomal breakage in response to DNA crosslinking agents. In addition to anemia, FA patients are highly predisposed to leukemia, head and neck squamous cell carcinoma, and gynecological cancers [3]. FA is caused by biallelic or X chromosome-linked mutations in one of 15 different genes, eight of whose gene products (FANCA, FANCB, FANCC, FANCE, FANCF, FANCG, FANCL, and FANCM) form a nuclear core complex that must be intact to ubiquitinate FANCD2 and FANCI. The ubiquinated FANCD2/FANCI heterodimer then functionally interacts with down-stream FA proteins (FANCD1/BRCA2, FANCJ/BRIP1, FANCN/PALB2, FANCO/RAD51C, and FANCP/SLX4) to mediate DNA damage responses [4]. This special issue provides a wide range of scientific papers and reviews that examine in detail techniques for diagnosis of FA, molecular and genetic mechanisms of FA protein function, comprehensive details of the varied clinical manifestations, new model systems for study of this disease, and potential new therapeutics. Three papers describe FA relevant aspects in FA diagnoses using chromosomal breakage analysis and mutation detection by multiplex ligation-dependent probe amplification (MLPA) and PCR-based Sanger sequencing, or next generation sequencing. The strategy to detect mutations and the genetic counseling of involved families should be adapted when there is evidence for a founder effect, which results in a high prevalence of a common mutation in a specific population. In this special issue, Y. de Vries et al. provide evidence that FA-C patients with the FANCC c.67delG mutation in the Dutch and Canadian Manitoba Mennonite populations originate from a common founder. One impediment to FA research has been the relative lack of a murine model that truly recapitulates the severity of FA hematopoietic defects. In the data reported by J. H. E. Verhagen-Oldenampsen et al., Ercc1-deficient mice were used as model for FA-like bone marrow failure. Although no ERCC1 mutations have been detected in FA patients, ERCC1 interacts with FANCP/SLX4 and functions in interstrand crosslink repair [5], the critical type of DNA damage recognized and repaired by the FA/BRCA pathway [6] (Figure 1). Figure 1 Schematic overview of the FA pathway. The FA pathway operates to maintain genomic stability in response to stalled replication forks, particularly in the context of interstrand DNA crosslinks (ICLs) that covalently link the two strands of the DNA helix. ... Another group of papers in this issue provides detailed and thorough scientific reviews of the varied clinical and molecular aspects of this disease, new model systems, and potential future treatments. First, the review by M. D. Milsom et al. details FA-associated defects in hematopoietic stem cell biology and resultant bone marrow failure. FA chromosomal aberrations associated with clonal evolution and leukemic transformation are the focus of the review by S. Meyer et al. T. Kaddar and M. Carreau review aspects of FA protein function that have been placed in the shadow by the recent focus on the role of the FA pathway in DNA repair. The paper by C. Hodson and H. Walden comprehensively reviews aspects of protein interactions and function in the FA core complex, while the review by M.R. Jones and A.M. Rose focuses on utilization of a relatively new model system for FA, the worm C. elegans. They examine the functions of DOG1, a functional ortholog of FANCJ, and FANCD2 in interstrand crosslink repair. To conclude the special issue, Jenkins et al. summarize the efforts that have been made to generate and utilize FA pathway inhibitors as novel anticancer therapies. The great progress in understanding FA on a molecular, cellular and clinical level illustrated in this special issue has made a big difference to people affected by FA, but also an enormous contribution to hematology, cancer, and developmental biology research. This has been achieved to a large extent through close interactions between scientists, clinicians and patients, which provide a resourceful platform for not only exchange and stimulation, but also a constant reminder of the goals of this research—aiming to understand biology in order to make the journey of families with FA a more hopeful one. FA Patient Support Groups by Bob Dalgleish, Fanconi Hope, UK — FA patients, although relatively few in number in each country, are fortunate in having a number of strong family support groups that coordinate their activities on an international basis to ensure a coherent approach to supporting research. The longest established group, the United States-based Fanconi Anemia Research Fund (FARF: http://www.fanconi.org.uk/) has been responsible for sponsoring a significant amount of research for over 20 years. Also in existence over a similar period, the German group Deutsche Fanconi-Anamie-Hilfe e.V. (Fanconi Anemia Aid Association: http://www.fanconi.de/), has been actively involved on an international scale in long-term research programs. The more recently formed UK-based organization, Fanconi Hope (http://www.fanconi.org.uk/) has been supporting research through the auspices of the FARF Scientific Advisory Board, for UK research projects selected by FARF. Fanconi Hope and FARF also sponsor an International FA Gene Therapy Working Group, now in its third year, which aims to accelerate the transition from research to gene therapy trials for FA patients by coordinating activities on an international scale. FA patients, their families and friends are in large part responsible for raising the funds for this research. This is of great benefit to those affected as this allows them to believe they can make a difference, if not to the current generation of FA patients then at least as a legacy to the benefit of the next generation. Laura E. Hays Stefan Meyer Henri J. van de Vrugt

Background. Patients in West Africa where sickle cell anemia (SCA) is endemic have for ages been treated with natural products, especially herbs, as, is still the case in rural communities.Objective. In this paper we look closely at some of these herbs to see if there are any lessons to be learnt or clues to be found for optimizing the treatments based on them, as had been done in the case of NIPRISAN, which was developed from herbs in Nigeria based on Yoruba Medicine.Methods. Select publications on SCA, its molecular biology and pathology, and actual and experimental cases of herbal treatment were perused in search of molecular clues that can be linked to chemical constituents of the herbs involved.Results. The study revealed that during the last 2-3 decades, much progress was made in several aspects of SCA pharmacology, especially the approval of hydroxyurea. As for SCA herbalism, this paper revealed that antisickling herbs abound in West Africa and that the most promising may yet be found. Three new antisickling herbs (Entandrophragma utile,Chenopodium ambrosioides, andPetiveria alliacea) were reported in May 2011. At NIPRD, where NIPRISAN was developed, three other recipes are currently awaiting development.Conclusion. The study raised the hope that the search in the Tropics for more effective herbal recipes for managing sickle cell anaemia will be more fruitful with time and effort.

Background: Relatively little information on secondary cancers is available for Non-Hodgkin lymphoma (NHL) treated patients as treatments have been less effective compared to those for Hodgkin Lymphoma. Recently, evolving chemotherapy (CHT) in combination with monoclonal antibodies, sometime supplemented with radiotherapy (RT) have improved survival outcome of NHL patients and the use of autologous and allogeneic bone marrow transplantation for relapsed patients have further improved long term survival for some histological subtypes. As a results of these advances secondary malignancies are becoming an important issue in NHL survivors. Design and Methods: In the last few years, our group performed 4 researches about second neoplasms in NHL survivors: (1) Secondary malignancies after treatment for indolent NHL; (2) Secondary malignancies after treatment for Diffuse Large B Cell Lymphoma (DLBCL); (3) Meta analysis on the risk of second malignancies in NHL survivors; (4) Incidence of second myeloid malignancies (SMyM) in patients treated for NHL, evaluated on Modena Cancer Registry (MCR) database. Results: In the first study we analyzed 563 patients with indolent NHL enrolled in Gruppo Italiano Studio Linfomi (GISL) trials from 1988 to 2003; results showed that, after a median follow-up of 62 months, 39 patients (6.9%) developed secondary cancer (12 Myelodisplastic Syndrome (MDS)/Acute Myeloid Leukemia (AML), and 27 solid tumours). The cumulative incidence (CI) of secondary cancer at 12 years was 10.5%. In the second paper we considered 1280 patients with DLBCL enrolled in GISL trials from 1988 to 2003; with a median follow-up of 51 months 48 patients (3.8%) developed a second cancer (8 MDS/AML, 5 other hematologic malignancies and 35 solid tumours). The CI of second cancer was 8.2% at 15 years. The third research consist in a meta-analysis in which we carried out an electronic search seeking articles investigating the risk of second malignant neoplasm (SMN) after NHL treatment; we have found 1,521 papers and after selection we considered 19 studies available for our aims. Our results indicated that NHL patients experienced a higher risk for SMN (1.88-fold increased risk) than the general population, in particular the standardized incidence risk (SIR) for secondary AML was 11.07. In province of Modena in the period 2000-2008 we found that the SIR to develop a second tumor after NHL was 1.63 and it grew up for second haematological malignancies (SIR 1.99). As concern the incidence of MDS and/or AML in Modena province on MCR we found a total of 9 NHL with SMyM (3 AML and 6 MDS) with a higher risk than expected (SIR 8.8, 95% CI: 4.0-16.6), in particular the SIR for secondary AML was 5.7. Conclusions: Overall our results observed either in patients enrolled in clinical trials or on database from hospital and population registry showed an increased risk to develop a second tumour in CHT/RT-treated patients. By meta-analysis, more impressive results have been observed considering only SMyM . Data from MCR confirm the trend for NHL treated to be at higher risk to develop SMN and in particular SMyM . In conclusion patients treated for NHL are at increased risk to develop secondary neoplasm. Thus for NHL survivors a long term monitoring should be considered with a follow-up longer than five years as usually.

In the article, "Evaluation of lymphocyte levels in a random sample of 218 elderly individuals from Sao Paulo city" by Teixeira et al.,(1) the authors measured percentages of CD4, CD8 and CD19 in blood from a population of 218 randomly selected elderly individuals of both genders aged between 60 and 101 years from Sao Paulo, Brazil. Participants were grouped according to their ages. Results showed significant differences in all age groups between males and females, especially in respect to the CD4/CD8 ratio which was significantly higher in females. No significant differences among age groups were found, except for the CD19 percentage in men which was lower in some elderly. The major point of the paper is that elderly men showed more changes in lymphocyte subsets than elderly women, in particular lower CD4 and higher CD8 percentages in all age groups. The authors suggest that the lower CD4 percentages in elderly men may account for reduced T cell help to B cells, whereas higher CD8 percentages may be a consequence of increased chronic inflammation observed during aging. These suggestions may be very relevant to health conditions but would need to be supported with functional experimental results. It will be interesting in future studies, to better characterize the lower CD4/CD8 ratio in elderly men, to investigate if CD* T cell homeostatic proliferation occurs in this population of very elderly individuals and if it is associated with lymphocyte activation and subpopulation changes, e.g. the CD8+CD28population, which has been shown to increase with age but is associated with less function.(2,3) The lower CD4/CD8 ratio was described years ago associated with persistent cytomegalovirus (CMV) infection and increases in the numbers of CD3+CD8+CD28-cells.(4,5) These measures were used to identify the immune risk profile (IRP) of very old individuals between 86 and 94 years of age(6) and predicted shorter survival in elderly patients. In the Swedish studies, OCTO(7) and NONA,(8) the prevalence of individuals with a lower CD4/ CD8 ratio increased from 8% in under 60-year-old individuals to 16% in over 60-year olds. The mortality rate in individuals with a lower CD4/CD8 ratio also increased significantly in over 60-year old individuals as compared to younger controls. Interestingly, the proportion of individuals with a lower CD4/CD8 ratio was found to be significantly higher in men(9) as shown in the current paper from the Brazilian group. One importance of this paper is the relevance for the whole human population; data collected from populations in different geographical areas are comparable. The Brazil study, like the Swedish NONA study, did not exclude individuals with reduced health. In the NONA study, this was justified by the need to achieve equal numbers of participating individuals in the 86, 90, and 94 age categories. In particular, only 9% of the individuals in the NONA study met the SENIEUR protocol criteria, a very strict protocol to exclude all diseases affecting the immune system.(10) Conversely, 35% of the individuals met the criteria used in the previous OCTO study(11) in which participants were included even though they had mild cognitive dysfunction as long as they did not have malnutrition and were not on anti-inflammatory, anti-viral or immunosuppressive drugs. Although the OCTO/NONA Swedish studies showed no significantly different results among nonselected, SENIEUR-selected or OCTO-selected individuals, it would be helpful to know the health conditions of those included in this work for future studies on this important population. Populations selected based on clinical information and laboratory data would also help to resolve different immunogerontological studies in human beings which have led to conflicting results. Moreover, the use of admission selection criteria minimizes the risk of including individuals with diseases that could influence the results by introducing exogenous variables. The Brazilian study also showed that B cells are significantly decreased in men and not in women. This result suggests that men could be more susceptible to infections or produce less protective antibodies after vaccination. Others have also shown decreases in B cell percentages and numbers with age, but to our knowledge no differences between genders.(11-15) Not only do the percentages of B cells change with age, but also the ratio among the different subsets in the CD19 pool changes(13,14,16) and this can help to explain why elderly individuals respond poorly to vaccination. The current study is an important study on human aging, with a unique population to establish the baseline values of lymphocyte percentages as affected by age. For the future it will be important to extend these studies to establish further information about either exclusion criteria for enrollment, and/or more detailed health information on participants, increased cell surface markers previously shown to be affected by aging, i.e. CD28 in T cells and IgG/IgA/CD27 in B cells (Figure 1), and further functional data, e.g. vaccine responsiveness, such as to the influenza vaccine. It would also be important to follow up with participants to track whether the decreased CD4/CD8 in males correlates with infectious disease, frailty, cancer, etc. Figure 1 The percentage of switch memory B cells IgG+IgA+CD27+ decreases with age. One hundred µL of blood from each subject were stained for 20 min at 4°C with anti-CD19, anti-IgG, anti-IgA, and anti-CD72 antibodies. After staining, red blood ... Developing and implementing vaccines to control infectious diseases in the elderly will require a more thorough understanding of the immunological mechanisms underlying the immune senescence across different populations, and how this is modulated by environmental parameters such as exposure to infectious agents. The discovery of biomarkers of aging will help predict which individuals will be able to respond to vaccination and design better adjuvants to improve vaccine responses and ensure effective disease prevention.

The "Revista Brasileira de Hematologia e Hemoterapia" (RBHH) is the only journal in our specialty south of the equator and one of two hematology and transfusion medicine journals in Latin America. It is the result of the progression from the old "Boletim da Sociedade Brasileira de Hematologia e Hemoterapia" and it is in its 12th year of existence. In this period our journal evolved naturally, but this development was less than what the scientific community wants and needs. Data presented by "Scopus" (www.scimagojr.com) show the remarkable evolution of scientific publications in our field within the international setting. We publish at a pace similar to the Chinese and more than India and all other emerging countries. In just ten years the number of indexed publications in Brazil grew about 10-fold, that is at a rate of 15-20% per annum. Moreover, it is important to note that only about 20% of these publications are linked to international trails; i.e., 80% are wholly Brazilian publications. All this is great, but still small. In spite of being the world's eighth largest economy, Brazilian Hematology and Transfusion Medicine is in 16th place in the ranking of indexed publications. There is no doubt, as the supplements on our two annual congresses (SBTMO and Hemo-ABHH) have demonstrated for several years now, as have data from European and North American Congresses, in particular the American Society of Hematology (ASH) that qualified national scientific production grows in the wake of the growth of the country because of increasing support from government grant agencies such as Conselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq), Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP) etc, and postgraduate programs, among many other reasons. In the last ten years or so, the RBHH has shown a very positive trend both quantitatively and qualitatively. The number of submissions has grown significantly and the publication indicators such as number of papers submitted and accepted, the time between submission and acceptance, the expansion of the editorial board, number of publications annually, the quality of the publication, submission on-line etc. are improving constantly. The presentation of the journal improved greatly and it is more pleasing for both readers and authors. But all this is little and is not enough. A reassessment of national scientific journals of Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES) was a true "cold shower" for the vast majority of periodicals, including the RBHH. The editors reacted and there is a consensus that perhaps the devaluation was exaggerated, but undoubtedly this serves as a warning to make changes and improvements. As everyone knows, 2010 was the first year of the formal foundation of the ABHH. Many challenges appeared during the merging process with "what should be done with the RBHH" being one of these very important decisions. After discussions within the Board of Directors, Editorial Policy Board, Executive and Scientific Editors, and many conversations and consultations with colleagues who have vast experience in publications in Europe, USA and Latin America, we believe that the RBHH has an important role in the continued education of the Hematology and Transfusion Medicine community, but that it should move towards offering a real and valid publishing option for physicians, health professionals and scientists working in this area. Thus a process to identify problems and find employees who could assist us in this transformation began. A working committee was created of technical advisors together with the editorial staff of the journal including professionals from Scientific Electronic Library Online (SciELO), Biblioteca Virtual em Saude (BIREME), a native English-speaking translator, the companies Trasso (which has worked with the marketing and publishing of the RBHH for several years) and GN1 (specialized in indexing in PubMed. Additionally, it was decided that the journal should have its own Digital Object Identifier (DOI) - a number used to uniquely identify electronic documents - among other things. It was decided that all articles published in 2010 (Volume 32) should be translated to English in order to index the journal in PubMed Central, thereby gaining international visibility with access to the articles. In this process the authors are not being requested to translate their articles, just to check and approve the final text. Even so, the biggest challenges have been saved for 2011. It will not be easy and we are not totally sure of being successful in this venture. Basically this editorial is the way I found to communicate a request to the Brazilian Hematology and Transfusion Medicine community. Volume 33 (2011) must be the best ever. There will be two versions of all regular issues (six per year): one printed in English and the other, an electronic edition, in both English and Portuguese. All papers should be submitted and published in English, as this, we believe, is central to being accepted by PubMed and ISI. The structure of the journal is being carefully reviewed and adjusted to comply, when possible, with all the requirements for future indexing in the most important databases of the world. Through the directors of the association and other researchers, contact was made with many colleagues in countries of the northern hemisphere and Latin America asking them to submit papers and participate in the peer review process. Nationally, we invited colleagues, who can decisively contribute to this process, to participate in this transformation. What we know is that we must be more competent and accurate in all phases of the complex editing process. Only then will we have a competitive and respected scientific journal. Indeed, Brazil has a significant number of doctors, health professionals and researchers who can and should publish in the RBHH and I know that the success of this decision depends on the scientific community as I know, as a professor and academic that we always try to publish in the best journals. This is natural and correct. But this time, we may decide to be only observers of our history or, who knows, to change the history. An internationally distributed journal of hematology and transfusion medicine can create scientific opportunities not only for Brazilians, but for many emerging countries around the world. Within the new global scenario, Brazil is becoming a prominent player within the scientific setting; we have much participation and Brazilian Universities are being recognized as some of the world's best, we cannot passively wait. The ABHH would like to catalyze this inexorable advance in Brazilian Hematology and Transfusion Medicine. The RBHH can be the scientific vehicle of this ongoing transformation that will be carried on by our young researchers guided by our medical colleagues, professors and scientists. Let's invest in these changes because we believe in them. I urge everyone to participate. Prepare your manuscript, submit to the RBHH, participate in this challenge that is ours.

Perforin (PRF) is a soluble cytotoxic pore-forming glycoprotein that is a crucial component of the cocktail of cytotoxic granules harbored by cytotoxic T lymphocytes (CTL) and natural killer cells (NK), collectively known as cytotoxic lymphocytes (CLs). CLs are able to detect virus-infected or transformed cells and destroy them through perforindependent mechanisms and death receptor-dependent pathways. The cell lytic pathway also involves the interaction of perforin and other granule toxins, particularly those of the granzyme family of cytotoxins.(1) Perforin is encoded by the PRF1 gene located in chromosome 10q22 in humans. PRF1 gene is approximately 6 kb long and is composed of three exons and a promoter region of 1409 bp.(2) Deficiency of PRF results in severe immunodeficiency in both mice and humans. PRFdeficient mice are pathologically susceptible to many viruses and develop B cell lymphomas.(3) Deficiency of PRF in human infants leads to an aggressive immunoregulatory disorder called familial hemophagocytic lymphohistiocytosis (FHL) that appears within the first few months of life. FHL is fatal unless treated with cytotoxic drugs followed by bone marrow transplantation. Partial deficiency of PRF leads to a late-onset form of FHL characterized by the appearance of various forms of hematological malignancies, including B and T-cell lymphomas, and acute and chronic leukemias.(1) These data strongly suggest that deficiency of CL function due to PRF deficiency has a critical role in the increased incidence of cancer. Sixteen allelic variants of the PRF1 gene, which result in perforin deficiency, have been described (OMIN # 170280). These variants are determined by point mutations and base deletions in the coding region of the PRF1 gene. In homozygosis these variants result in reduced expression or in the synthesis of a truncated protein. Three variants (W374T, N252S and A91V) are clearly linked to the development of hematologic cancers. The A91V allele is the most prevalent variant in the Caucasian population with a reported frequency of between 3 and 17%. The A91V frequency is very low in African-Americans and there are no reported cases of this polymorphism in Japanese subjects. The A91V polymorphism has also been proposed to predispose patients to B and T-cell lymphoma, acute lymphoblastic leukemia, anaplastic large cell lymphoma, and Dianzani autoimmune lymphoproliferative disease. In a large epidemiological study, an increased incidence of the A91V mutation was found in BCR-ABL positive ALL patients indicating the necessity to investigate the effect of the presence of the A91V allele in a large cohort of cancer patients. The importance of the association of PRF function and the predisposition to hematological cancer was recently emphasized by Chia et al. who conducted a study in a cohort of patients with atypical or delayed FHL type 2.(4) The authors found a frequency of hematological cancer of over 100 times higher than that reported in the general population and argue in favor of the important role of PRF in the immune surveillance of cancer. PRF deficiency occurs not only with allelic variants characterized by mutations in the coding region of the gene. McIlroy et al. reported that the occurrence of a C/T polymorphism at position -398 of the proximal promoter region of the PRF1 gene was associated with decreased quantities of PRF in CTLs in HIV infected patients. A decrease of about 50% of control PRF levels was observed in heterozygous patients but no patients homozygous for -398T/T mutations were studied.(5) In this issue of the Revista Brasileira de Hematologia e Hemoterapia, Garcia et al.(6) present an analysis of the frequency of the C398T polymorphism in a cohort of 62 patients with hematological cancers that had no allelic disequilibrium when compared to control populations matched by inferred ascendency. However, they describe an excess of the C398T polymorphism in the patients taken as whole group compared with the controls. This discrepancy could be attributed to the small number of patients studied or to the criteria used to define the control population. It is worth mentioning that all patients, except for one, were heterozygous (C398T). The only homozygous patient has myelodysplastic syndrome, but unfortunately the corresponding clinical and epidemiological data were not included in the paper. Overall, the paper raises a number of important questions related to the role of PRF in hematological cancer and some points should be addressed in future studies: 1. Is the level of PRF reduced in the cancer patients studied as observed in HIV infected patients? 2. Is the CTL response of the lymphocytes of patients with the allelic variants normal when compared to patients with wild type and normal individuals? 3. What is the prevalence of the coding allelic variants in this group of patients? To clarify these important points it is necessary to increase the population enrolled and perform the entire PRF1 gene sequencing of patients and matched controls. A multicenter study would be welcome.

By contributing new knowledge to a particular area of science, the publication of scientific articles is the primary objective of research projects and of the researcher. The systematic planning of a project, obedience to every step of the research protocol makes sure that the results found, whether relevant or not, are accepted by the scientific community. The result of this work will always be the publication of a scientific paper. Afterwards the author submits his contribution to a peer-reviewed scientific journal, either within his field or to a more prestigious journal, for publication. In several editorials, the Revista Brasileira de Hematologia e Hemoterapia (RBHH) has discussed the Qualis classification system of the Coordenacao de Apoio aos Profissionais do Ensino Superior (CAPES) and its effects on the Brazilian academic community(1,2). Unhappily this system punishes almost all Brazilian authors but, in particular, those that publish in journals dedicated to their specialty such as the RBHH. As the lay press reported the classification system puts Brazilian scientific journals at "risk of extinction"(3). On the subject of Brazilian scientific journals, editors on several occasions have disagreed with the use of the impact factor of Institute for Scientific Information (ISI) Thomson Reuters JCR to evaluate Brazilian scientific production(4). Moreover, data showing the geometric growth of the number of scientific publications in Brazil and relatively low number of citations of national studies were presented in the last editorial(5). Recently, via the scientific publishers list of the World Association of Medical Editors on the web, journal editors from diverse areas have been condemning cases of plagiarism and duplicate publications(6). Furthermore they criticize the cutting up of data resulting from a single research project with the goal of increasing the number of publications of one specific author or group of authors, a technique that received the facetious name of 'salami science'. Although distinct, articles and texts have recently appeared in the lay press on both these subjects(3,7). The articles about CAPES were not complimentary to this government institution. In fact, discussions about the position of CAPES in respect to the evaluation of scientific production have been circulating in the scientific corridors for a few years now. Debates condemn its policies, but it seems that nothing really changes. One of the major concerns of bureaucrats, who have little or no knowledge of true scientific research, is the need to systematically measure the worth of scientists. How do we decide, for example, whether researchers deserve promotion, pay increases, more political clout or even that grant that they have applied for? To do this, government intuitions around the world are using the number of publications and the impact factor, an index developed to compare journals and not authors. Does this make a difference? This has created the 'Publish or Perish' culture which includes 'Salami Science'. Whether duplicate publications (which the RBHH does not accept) are ethically correct or not can be argued. Although this may waste the reader's time and, for example, distort the overall results of database searches, it seems that there may be ethical support for this practice when the author truly believes that his work will make a difference in the quality of patients' treatment. Certainly publications in different languages should not be frowned upon as most practitioners in non-English speaking countries do not speak English. This is definitely the case of Brazil where even the aforementioned government institution, CAPES, encourages all to publish in English with no importance whatsoever given to the native language. This it does by a points system where articles that are not published in ISI are assigned a very low number of points and only three articles are included in an author's scientific production evaluation. Even articles published in PubMed, for many researchers the preferred source database for research, receives half the points of an article published in the lowest ISI classification. Furthermore, splitting a long arduous paper into simpler parts can be helpful not only to the understanding of readers but also to increase the spread of knowledge. Unfortunately today we are living in a world where people are reading less and less due to culture changes related to the modern way of life. Many individuals, including physicians, are not used to reading complicated articles anymore and either get lost in the middle, lose patience or both and so, many long articles remain relatively unread. Perhaps we should change our opinions on this subject. And this leads me to the most important question - why do we publish? There are numerous reasons but the most common in medicine are to improve patient care, to exchange knowledge with other researchers and to improve academic careers. Of course our egos do not suffer from a good publication too. One imagines that the primary goal of medical publications should be to improve treatment for patients. It seems fairly clear that the best way to achieve this end is to make knowledge widely and freely available to all practitioners, independent as to whether they are university professors, researchers or the ordinary physician in a small town in the middle of nowhere. We know that today the changes in medicine are rapid and that lifelong learning is essential to keep up, but for many this is not possible as the information is not readily available. All researchers would like to publish in journals with the highest impact factors. Of course this, as renowned researchers seek to publish in The Lancet, JAMA, Nature and the New England Medical Journal, perhaps artificially and definitely wrongly, consolidates the position of the elite journals at the top. The reason I suggest this is as follows. As initially the ISI, the fore runner of Thompson Reuters, the 'owner' of the Impact Factor, only included journals published in English, this gave the North American and British journals a head start, they had impact factors before any 'foreign' journal even thought about publishing in English. As the impact factor became important to their careers, 'top' researchers obviously invested in trying to publish in these journals. Moreover, the Lancet, JAMA, Nature and the New England Medical Journal are journals that cover all fields in medicine. This gives them a much greater opportunity of finding articles that they believe will be cited. However, for most everyday practitioners, these 'elite' journals are not the first choice. Most practitioners want all the information in one place, concentrated and at a low cost (or free) and therefore subscribe to a journal of their specialty. Hence, it seems that most authors who submit to these 'top name journals' perhaps do so, not to spread knowledge to improve the health of the population, but for their own careers. With the attitude of CAPES can we blame them? Even HINARI, the Access to Research Initiative, in which the RBHH participates, started in 2002 by the WHO and major publishers, although a very good start, has its flaws as only medical and nursing schools, universities and research institutions in developing countries have access and not to all journals(8). After a physician leaves medical school, is he no longer entitled to have access to new advances in medicine? But perhaps the solution to this problem is around the corner. Until now many articles are published in more than one database (SciELO, PubMed, ISI and in smaller databases) and also in the site of the journal itself. This distorts any calculation of the impact factor and limits it only to articles published in ISI. With the creation of the digital object identifier (DOI) the next logical step is to create a new manner to really identify the importance of scientific publications that is independent of the database or databases in which an article is 'published'. Furthermore, with the simplicity of analysis using the World Wide Web, all articles can be broken down to their source articles giving all due respect to the real discoverer of new knowledge and not just to the people who report it in review articles.

Since 1999 blood transfusion services around the world have been implementing nucleic acid amplification tests (NAAT) to screen for hepatitis C (HCV) RNA, human immunodeficiency virus (HIV) RNA and hepatitis B (HBV) DNA to improve the safety of the blood supply. Initially HCV RNA and HIV RNA NAAT screening was implemented and more recently HBV DNA NAAT screening commenced. In the beginning mini pools (MP) of 98 were used due to the manual complex systems available which were not suitable for high throughput because of the stringent laboratory requirements(1). Over the years the pool sizes have decreased to either 16 as used in the USA(2) or even smaller such as 6 as used by many European and Asian countries(3-5). South Africa, in 2005, was the first country in the world to implement individual donation (ID) screening for all three viruses of all donations(6). NAAT screening in parallel with serological screening has allowed the classification of HIV positive donations as window period, concordant and elite controller infections. HCV positive donations can be classified as window period, concordant and resolved infections and HBV positive donations can be classified as Window period, HBsAg only, acute concordant, occult and anti-HBc only infections. Since the implementation of NAAT for HBV DNA screening, vaccine breakthrough infections have also been recognized(7). The article in this issue of the Revista Brasileira de Hematologia e Hemoterapia (RBHH) entitled One window-period donation in two years of individual donor-nucleic acid test screening for hepatitis B, hepatitis C and human immunodeficiency virus by Levi et al. describes the first two years of screening for HIV RNA, HCV RNA and HBV DNA using ID NAAT in a small Brazilian blood center(8). From a total of 24,441 donations, no additional yield was obtained for HIV and HCV and they showed a 35% clearance rate for HCV and no elite controllers for HIV. The primary objective of the paper is to describe an unusual HBV yield case. This case tested HBsAg and anti-HBc negative and had an anti-HBs titer of 18 IU/mL. On follow up, the anti-HBs rose to 109 IU/mL, however in four samples over seven months no HBsAg or anti-HBc reactivity occurred. Sequencing confirmed the donation as a genotype A2 vaccine breakthrough infection. This is unusual as most documented breakthrough infections have been of the non-A2 genotype due to the vaccine comprising an A2 virus(7). The authors also showed 19 cases of HBsAg positive with no other HBV marker reactivity. It would be interesting to understand whether the authors viewed these donations as true or false infections in light of the investigations being done in the USA in the context of potentially removing HBsAg screening if HBV NAAT and anti-HBc screening is performed. Although this paper describes a small number of donations screened by ID-NAAT, if extrapolated to the larger Brazilian donor base and the prevalence and incidence is similar to that presented by Levi et al., then ID-NAAT could have a large impact on the safety of the blood supply particularly for HBV and HIV due to the high prevalence and incidence of the diseases, respectively.

Desde que se comenzó a realizar el trasplante hematopoyético se reconoció la importancia de conocer el establecimiento de quimerismo. El presente trabajo actualiza los conceptos de quimerismo, su clasificación y las diferentes vías para su determinación. Se destaca como la más recomendada, la amplificación de zonas altamente polimórficas en el ADN por la técnica de la reacción en cadena de la polimerasa. La utilización de esta técnica ha permitido realizar estudios de la evolución de la quimera, relacionar el grado de quimerismo establecido con el comportamiento del injerto y de la enfermedad de injerto contra hospedero en los diferentes regímenes de acondicionamiento. También ha posibilitado la detección precoz de la recaída en los pacientes trasplantados y la administración oportuna de inmunoterapia adicional. Finalmente, se presentan las recomendaciones de la Sociedad Americana de Trasplante de Sangre y Médula Ósea para estandarizar el estudio del quimerismo en los diferentes centros de tratamientoSince the hematopoietic transplantation was performed for the first time, the importance of knowing chimerism was underlined. The present paper updates the concepts of chimerism, its classification and the different ways to determine it. The most recommended is the highly polymorphic area amplification in the DNA using the polymerase chain reaction technique. This technique has allowed carrying out studies on the evolution of chimera, to relate the set level of chimerism with the graft behaviour and the graft-versus-host disease under different conditioning. It has also made it possible to early detect relapse of transplanted patients and the prompt administration of additional immunotherapy. Finally, the paper presents the recommendations of the American Society of Blood and Bone Marrow Transplantation for standardizing the study of chimerism in the therapy centers

Science is ever changing and so is medicine. Some certainties today may not be valid tomorrow. New research, observations and outcomes can turn widely used current practices into no longer acceptable ones. Additionally, and especially in medicine, one may find more than one right answer to the same problem. Different physicians, with different backgrounds, may choose different ways to address a clinical situation. Through medical conferences and peer reviewing, these 'uncertainties' can evolve into safer practices, as one's experience can add to others'. Blood transfusions have never been safer. Through the addition of new and powerful technologies and practices, the use of human blood is an efficient and safe therapeutic option, as long as it is correctly applied. But what can be considered the "correct use" of such a tool? Since the 1960s it is current practice in different medical centers, particularly in the US, to have a medical committee to review the indications and usage of blood products: the Transfusion Committee (TC). This is also recommended by different institutions, including Advancing Transfusion and Cellular Therapies Worldwide (AABB - formerly American Association of Blood Banks)(1), and the Joint Commission on Accreditation of Healthcare Organizations (JCAHO) both in the USA. More recently, it has also become a demand of the Brazilian Ministry of Health and was included in the latest "Technical Regulations in Hemotherapy Practice"(2). The precise objectives and composition of the TC may vary between institutions and governmental regulating agencies. For AABB, it should be "a peer reviewed program that monitors and addresses transfusion practices for all categories of blood products". For the Brazilian Ministry of Health, it should be "a multidisciplinary committee that monitors hemotherapy practice, including education, hemovigilance and the definition of protocols for transfusion practices". Mintz states that "the clinical staff governing body from each hospital must decide how it wishes to assess transfusion practices"(3). The benefits of blood transfusions are well established. Inappropriate use, however, should be reduced to a minimum, as the inventories are permanently on the edge, the products are finite and hard to obtain, and making human blood a safe product for therapeutic use is a very expensive process(4). It should also be remembered that adverse effects are still present and should be carefully considered when physicians prescribe blood. A multi-specialty medical group allows teamwork, open and transparent communication and maintains clinical practice aligned with current medical knowledge. Clinical practice is complex, and certain clinical situations go beyond the individual's knowledge and ability. A TC should ideally operate in accordance with the institution's general practice standards. Its president is normally nominated by the Hospital's board of directors, and it should meet and report periodically according to the individual local needs. Some advocate that the president should not be a representative from the blood bank, in order to avoid conflicts of interest. However, at least a blood bank physician should have a seat in the TC. Important participating specialties include anesthesiology, surgery, intensive care, nursing, among others to be defined locally. The main task of the TC is to promote a safe and effective use of blood products. It should also assist in developing transfusion policies, obtaining compliance from prescribing physicians,facilitate collaboration between disciplines, evaluate the implementation of new techniques,support training and education of medical teams and help spreading blood banking practices. Reviewing the use of blood products in the institution is another common major task of the group. The excessive and/or inadequate use of blood can be monitored, as well as adverse reactions. Having the committee's support to implement guidelines in hemotherapy is of major importance to help the blood bank achieve this goal. While some groups focus on a clinical approach of TCs, others advocate that the TC should be involved in internal technical activities of the blood bank as well. In this issue of Revista Brasileira de Hematologia e Hemoterapia, Carvalho et al. bring a comprehensive and interesting study of a large number of transfusion agencies operated by, or associated to, Hemominas, a major public blood center in Brazil, operating in 178 different cities in the state of Minas Gerais(5). These agencies' activities were analyzed according to the presence or not of an active TC and its influence on different internal, technical and clinical practices in different hospitals. Results show that centers with an active TC not only have better notification and follow-up of transfusion reactions, but also better internal clinical practices, such as correct filling out of paperwork and patient transfusion data, and better blood sample identification processes. It is interesting to note that is hard to know whether an active TC is the main determinant for a more strict implementation of guidelines and regulations, or if the institutions that are better at following guidelines happen to be the ones that have adopted more active TCs. The bottom line is that this paper brings light not only to the current situation of TCs in a major Brazilian state, but also to the technical practice of blood transfusions in a large number of institutions. As stated in the paper, these findings should serve as a basis to approach the problem. Whether identifying, monitoring and pushing for corrections of technical deficiencies in blood banks is a task of the authorities and/or of the TCs remains a matter of debate. However, evidence from the present work shows that TCs have an important role in today's blood banking practices.

Luca Castagna,1 Armando Santoro,1,2 Carmelo Carlo-Stella1,2 1Humanitas Clinical and Research Center, IRCCS, Rozzano, Milan 20089, Italy; 2Humanitas University, Department of Biomedical Sciences, Pieve Emanuele, Milan 20090, ItalyCorrespondence: Luca CastagnaHumanitas Clinical and Research Center, IRCCS, Via Manzoni 56, Rozzano, Milan 20089, ItalyEmail luca.castagna@humanitas.itAbstract: Relapse/refractory Hodgkin lymphoma patients are still a clinical concern. Indeed, despite more effective first-line chemotherapy regimens and better stratification of unresponsive patients by clinical factors and use of early PET, roughly one-third of such patients need salvage chemotherapy and consolidation with high-dose chemotherapy. In this paper, the authors review the different salvage treatments, with special emphasis on newer combinations with brentuximab vedotin or check point inhibitors. The overall response rate is constantly increasing, with a complete remission rate approaching 80%. Functional response evaluation by PET imaging is a strong predictive factor of longer survival, and more sophisticated tools, such as detection of circulating tumour DNA, are emerging to refine the disease-status assessment after treatment. Consolidation by high-dose chemotherapy is still considered the standard of care in chemosensitive patients, leading to a high fraction of patients towards long-term disease control. Maintenance therapy with BV is now approved, reducing disease relapse/progression. An increasing number of Hodgkin lymphoma patients will be cured after first- and second-line therapy, and long-term toxicity needs to be continuously assessed and avoided.Keywords: Hodgkin lymphoma, refractory/relapsed disease, checkpoint inhibitors, brentuximab vedotin, high-dose chemotherapy

Sickle cell disease (SCD) affects nearly 100,000 people in the United States of America and the sickle gene is present in approximately 8% of black Americans. Among Africans, the prevalence of sickle cell trait (heterozygosity) is as high as 30%. While SCD occurs among varying racial and ethnic groups, it is more commonly prevalent in individuals of African or African-American descent. This inherited blood disorder causes varying symptoms and complications among affected children and adults and early diagnosis and treatment are essential to help reduce mortality rates. Because there is no cure for SCD, management is vital to survival. Hence, there are different approaches in use to aid those living with SCD; thus, this paper provides insight into the current methods that are implemented in the management and maintenance of this disease.

BackgroundPancreatic cancer continues to be one of the most aggressive malignant tumors. Work in recent years in cancer molecular biology has revealed that metabolic reprogramming is an additional hallmark of cancer that is involved in the pathogenesis of cancers, and is intricately linked to gene mutations.Main textHowever, though oncogenes such asKRASandc-Mycplay important roles in the process, and have been extensively studied, no substantial improvements in the prognosis of pancreatic cancer have seen. Therefore, some scientists have tried to explain the mechanisms of abnormal cancer metabolism from the perspective of tumor suppressor genes. In this paper, we reviewed researches about how metabolic reprogramming was regulated by tumor suppressor genes in pancreatic cancer and their clinical implications.ConclusionAbnormal metabolism and genetic mutations are mutually causal and complementary in tumor initiation and development. A clear understanding of how metabolic reprogramming is regulated by the mutated genes would provide important insights into the pathogenesis and ultimately treatment of pancreatic cancer.

Haemophagocytic lymphohistiocytosis (HLH) is a rare but potentially aggressive and life-threatening syndrome of overactive histiocytes and lymphocytes that commonly affects infants; it is also observed in children and adults of all ages. The disease is differentiated into either primary or secondary causes. Primary HLH tends to be of genetic origin, while secondary HLH results from either infection, autoimmune disorders, or malignancies. Secondary HLH is most commonly associated with viral infections in immunocompromised patients. This paper presents a case of HLH in a tertiary care hospital, associated with adult-onset Still’s disease, diagnosed on both biochemical criteria and histopathologic examination of bone marrow smear.

Background and Aims: The initial management of deep vein thrombosis is starting to happen in general practice. New treatments are available to allow this shift, but guidance is variable. The aim of this study was to understand current choices used in general practice in the UK and to determine if there is a more efficient treatment, considering variability observed locally. Methods: A systematic literature review and freedom of information requests to England’s 198 clinical commissioning groups (CCG) were used to gather information on treatment options and current uses, respectively. Over 100 papers were assessed, and information from 177 CCG was obtained. Results: There is noninferiority between injectable low-molecular-weight heparin and novel oral anticoagulant treatments. Fifteen CCG offered variable, but also limited, options of treatment. Patient choice was not necessarily considered. Conclusion: There is variability in England on availability and choice of therapy for the initial management of deep vein thrombosis at present, which may also be the case elsewhere. The implementation of evidence-based guidelines should be carefully considered in all settings and countries.

Secondary myeloid neoplasias are a heterogeneous group of diseases characterized by the proliferation of myeloid cells; they were recently recognized by the World Health Organization (WHO) as an entity. The wide use of chemotherapy and better diagnosis of hematological malignancies has caused a growth in the number of secondary malignancies. Most of them are myeloid: a) myelodysplastic syndromes (MDS), a heterogeneous group of clonal hematopoietic stem cell disorders characterized by ineffective hematopoiesis and dysplastic changes in bone marrow and peripheral blood with the risk of transformation to acute myeloid leukemia (AML) or b) sometimes the previous disease directly evolves to an overt AML. Usually the prognosis of patients with a secondary myeloid neoplasia is poor, especially when the previous disease is a MDS. However, patients may achieve a complete response. In this situation, progenitor stem cell transplantation is the best therapy. Cytogenetic analysis still plays a pivotal role in the diagnosis of hematological diseases. Cytogenetics and mutational analysis are the main prognostic tools in both AML and MDS. For this reason, cytogenetic studies are critical in the correct management of these diseases. There are several cytogenetic abnormalities associated with better prognosis, such as translocations involving core binding factors in AML patients, and losses in 20q, 5q or chromosome Y in MDS. In contrast, many others abnormalities are associated with dismal prognoses, such as the presence of a complex karyotype, abnormalities of either chromosome 3 or chromosome 7 and, in case of AML, the loss of the long arm of chromosome 5. All of these abnormalities are included in the new staging system for MDS (IPSS-2). Recently new data regarding the presence of abnormalities in chromosome 7 in primary MDS showed that the presence of a partial deletion of the long arm of this chromosome (7q-) is associated with a better prognosis than monosomy 7.(1) This abnormality is a common event in secondary MDS and AML and the potential value of this observation in secondary MDS should be addressed. In this issue of the Revista Brasileira de Hematologia e Hemoterapia a new observation highlighted the importance of performing cytogenetic studies in secondary MDS.(2) Over recent years, the wide use of microarrays and, more recently, the possibility of sequencing the human genome have provided new insights into knowledge of the molecular mechanisms involved in MDS and AML. Analysis of the gene expression profile by means of microarray technology demonstrated the presence of new pathways involved in the pathogenesis of these disorders, although studies focusing on secondary myeloid diseases are lacking.(3) Since the sequencing of the entire genome of the first hematological malignancy, a patient with AML,(4) several papers have shown the interest of the detection of new genes involved in these diseases.(5) Some of these papers have also described the involvement of new functions involved in myeloid diseases such as the spliceosome mechanism that could play an essential role in the genesis of both MDS and AML.(6) Therefore, near future investigations should provide more information of the genes involved in secondary myeloid diseases. The challenges will be to understand these genes which are thought to be drivers in the genesis of secondary myeloid neoplasias and, more importantly, to identify new therapeutic targets.

Clovis Pedro Junqueira, considered a living legend in transfusion medicine in Brazil died on October 2, 2011, at the age of 94 years. Until about 1 or 2 years ago, Professor Junqueira was still active, receiving honors and being interviewed and consulted about the future of hemotherapy in Brazil. He was seen in the library that bears his name at the headquarters of the Brazilian Society of Hematology and Hemotherapy (SBHH), studying, consulting international journals and the internet in order to keep himself up to date. It could not have been different: all his lifetime, Professor Junqueira devoted himself to transfusion medicine in Brazil; he scientifically and personally influenced several generations. The library of the SBHH should now receive in its collection, the books of this illustrious visitor, in fact many rare books in perfect condition were already donated while he was alive. Hematology will always have the works that he edited: 'the Essentials of Blood Transfusion', 'Peri-Natal Hemolytic Disease' and last year with Jacob Rosenblit and myself, 'Clinical Transfusion Medicine', a book that summarizes his philosophy of changing the transfusion medicine specialist inside the blood bank from someone who follows prescriptions to being active with colleagues of other specialties, and especially with his patients. Born in Sao Luiz, Maranhao on June 1, 1916, he was still a child he moved with his family to Rio de Janeiro, the then capital of the country. His Portuguese father was hoping to find opportunities in trade, but he became attracted to medicine and in 1939 he graduated at the National Medicine School of Brazil in Rio de Janeiro. He was a disciple of Walter Oswaldo Cruz and his training included stints in England, Germany, Holland, France, Argentina and the United States, as he passed in first place in the Postgraduate Course in Hematology at the Oswaldo Cruz Institute. In 1945, he began to devote himself to transfusion medicine and founded a service in Rio de Janeiro. Later, he joined Prof. Dr. Hildebrando Monteiro Marinho, merging hematology and transfusion medicine into one single unit. With Walter Oswaldo Cruz he gave the first course of specialization in hematology in Manguinhos in 1949. In the same year, he was one of the organizers of the First Paulista Congress of Hematology. The event started on June 8, lasted four days and produced 30 recommendations, including the establishment of the First Brazilian Congress. Along with Carlos da Silva Lacaz, Oswaldo Mellone and Michel Abu Jamra, he founded the Sociedade Brasileira de Hematologia e Hemoterapia (Brazilian Society of Hematology and Hematology), scheduling the First Brazilian Hematology Congress for the 21 to 26 of May 1950, at which time the society became official. Besides Pedro Junqueira Clovis, the organizing committee included Walter Oswaldo Cruz, Heraldo Maciel, Artur Cavalcante, Joao Maia Mendonca, Frederico Ottensooser, Oswaldo Mellone, Michel Abu Jamra, Ruy Faria, Carlos da Silva Lacaz, Menandro Novaes, Cortes Villela and Carlos Estevao Frimm. In 1951, Professor Junqueira presented papers on blood groups in Brazilian Indians in two international conferences in Portugal and Italy. In the same year, he participated in the creation of the Human Genetics Commission of the Brazilian Society of Genetics. In 1954 he led the Brazilian delegation to the Fifth Congress of the International Society of Blood Transfusion held at the Sorbonne in Paris. That same year, he worked on projects together with Jean Dausset and AE Mourant. Professor Junqueira was elected president of the Brazilian Society of Hematology and Hemotherapy for two consecutive terms; he worked very hard for the recognition of the specialty and was responsible for the acquisition of the Society's own headquarters. He was awarded honorary professor and honorary president of the Brazilian Society of Hematology and Hemotherapy. He also participated in several scientific societies and other entities, as full member of the Brazilian College of Surgeons, president of the Brazilian Society of Clinical Pathology, a member of the Advisory Board of the International Society of Blood Transfusion, member of the Human Genetics Commission of the Brazilian Society of Genetics, director of the Physician Continuous Education Center of the Department of Health, president of the Latin American Society of Hematology and a member of the Technical Division of Hematology of the National Health Council. Post-graduation professor of Hematology of PUC-RJ and former Regent Professor of Genetics, he gave six postgraduate courses, 20 courses on hematology, more than 170 classes, with more than 42 courses in his curriculum. Additionally, he published more than 40 scientific papers in prominent journals. It is important to note that Professor Junqueira is one of the few Brazilians with publications in the journal Nature in which he published three papers. He wrote and translated books, wrote chapters in books and several monographs. He participated in 70 national and 27 international conferences, including 24 meetings of the American Association of Blood Banks. In these conferences, he presented a hundred papers, participated in 85 round tables and gave 35 lectures. Throughout his career, he also received several other awards, including the Laboratory Prize of the Academic Society of Medicine and Surgery of Rio de Janeiro in 1939, the "Merit. Prof. Clementino Fraga" medal awarded by the Governor of Guanabara in 1974, Diploma of Great homage given by the Brazilian Society of Clinical Pathology, the title of Professor Emeritus of the Medical School of Teresopolis in 1987 and the Alfred Juazykowski Award by the National Academy of Medicine in 1998. In 1992, with a wonderful monograph on auto transfusion, he became a member of the National Academy of Medicine. In 2000, he was chairman of the XXIV Brazilian Congress of Hematology, celebrating the fiftieth anniversary of the Brazilian Society of Hematology and Hemotherapy. The competence and care, characteristics of Professor Junqueira were apparent in every detail of the scientific and social programs. His contribution to Brazilian transfusion medicine was so important that, at this time, he was honored by our colleague Marcos Pimentel Alfredo with a book about his life called: The Trajectory of a Master. In 2008, during a hospital stay, he became enthusiastic when he heard about the merger between the SBHH and the Brazilian College of Hematology to form the Brazilian Association of Hematology (ABHH). Even when Professor Junqueira was recovering from health problems, he did not forget and even continued to influence decisions in his field. More important than everything else, more important than any title or award, he was human; Clovis Pedro Junqueira, or Pierre Clochard as he liked to be called. Father, grandfather, loyal friend and wonderful husband, an enviable man of culture, fond of all the causes he embraced, he was an example and encouragement to us all. A fanatical supporter of Flamengo Football Club, admirer of a good whiskey and fine wine, Mr. Junqueira was married to Norma, the secret to his everlasting youthfulness. Professor Junqueira will always be remembered for his professional competence, wisdom, intellect, simplicity, humility and his "joie de vivre."

The paper by Ferreira et al. published in this issue of the Revista Brasileira de Hematologia e Hemoterapia(1) provides one of the rare quantitative assessments of the value of test results in external proficiency programs as indicators of quality in transfusion services. Essentially, services that participated in proficiency programs in Minas Gerais had significantly better performance on important immunohematology procedures than services that did not participate. Furthermore, a comparison of general parameters of quality compliance showed better attention to quality practices in the group participating in external proficiency programs than among those who did not participate. Unfortunately, a significant number of blood banks in both groups, participants and non-participants, had performance failures in the proficiency programs. Historically, external quality control programs in immunohematology, also referred to as proficiency programs, evolved from the initial desire of laboratory scientists to refine the accuracy and precision of their assays. They started sharing and exchanging blood specimens, discussed results at meetings, carried out "wet" and "dry" workshops, participated in working groups and committees, and ultimately defined the quality requirements adopted by standard setting organizations. The organizations established criteria, nomenclature and best practices for the identification of blood group antigens and antibodies that served as the basis for the assurance of immunologically safe blood transfusions. Despite progress, hemolytic transfusion reactions with tragic consequences continued to occur. Attempting to address this issue, strong willed blood banking leaders developed minimum standards and created voluntary accreditation programs based on inspections to assess compliance of blood banks with these standards. These accreditation programs were implemented in the United States in 1978, when the American Association of Blood Banks added the requirement for an external quality control program to its Standard.(2) All blood banks and transfusion services shall utilize a program of quality control that is sufficiently comprehensive to ensure that reagents and equipment perform as expected, and that there is compliance with these Standards. Each blood bank and transfusion service shall participate in a proficiency testing program. Thus, in order to receive accreditation, blood banks had to correctly identify red cell antigens and antibodies in blind specimens provided by an approved organization. Testing was performed according to the blood bank protocols and results submitted to the agency preparing the specimens. Results were fed back to the blood banks being tested. Unfortunately, as mentioned earlier, there are little published data measuring quantitatively the impact of introduction of accreditation and proficiency programs in the quality of transfusions and prevention of adverse reactions. The creation and expansion of regulatory agencies by local and federal governments around the world and the common-sense perception that accreditation and proficiency programs improved patient safety, led to the gradual change of these programs from voluntary to obligatory requirements for the operation of a blood bank and transfusion service. In the United States, this became a formal requirement with the approval of the Clinical Laboratory Improvement act of 1988 as part of the Public Health Law. The law essentially determined that clinical laboratories and blood bank laboratories had to be registered with the U.S. Department of Health and Human Services, had to comply with various regulations and could only perform complex tests and be paid if they were registered and passed inspections by the government or by deemed organizations. The successful performance of proficiency tests, e.g., obtaining accurate results on specimens provided by an approved organization became a fundamental requirement. Gone were the days when one blood bank physician could call another blood bank physician to discuss what was wrong with their results and what could be done to improve performance. Every blood bank had to participate in a proficiency program. Failure would mean no reimbursement for services performed and, in extreme cases, loss of the license to operate. There have been revisions of the law and of regulations over the years,(3) but the fundamental requirement for proficiency remains, and certainly the financial penalty of no reimbursement constitutes an important incentive for compliance. We all recognize that there has been a substantial improvement in the quality of testing and a reduction of fatal hemolytic reactions over the years and that many factors, including better management systems, computers, training and regulatory actions have contributed to that improvement. The data presented in the paper by Ferreira et al.(1) clearly shows the value of proficiency programs. However, it is surprising to verify that a large number of laboratories were able to operate despite erroneous results in proficiency testing. Even more surprising is the fact that a large proportion of blood banks failed to participate in the program despite the Brazilian regulatory requirements. The finding that one third of the non-participants obtained inaccurate results in antibody screening and 14.7%, or one in six, had inaccurate results on compatibility testing, the last step in the chain of measures that ensures transfusion safety is very concerning. I strongly believe that the publication of this manuscript will have a healthy impact on practitioners and regulators inside and outside Brazil. It will contribute to the improvement of transfusion practice in Brazil and will confirm quantitatively the value that good quality systems, good laboratory practices and participation in proficiency programs bring to the safety of transfusion recipients.

An amendment to this paper has been published and can be accessed via the original article.

Background and Objectives: With no proven treatment guidelines for COVID-19, human convalescent plasma is an option and has been under trial worldwide. In India, Indian Council for Medical Research (ICMR), started a Mulicentric Trial for the use of convalescent plasma in the treatment of COVID patients. The purpose of this paper is to analyse the challenges encountered in the collection of convalescent plasma from COVID recovered patients at a trial site. Methods: The current prospective study was carried out in a tertiary care hospital based blood centre catering to COVID patients and a trial site for Plasma therapy by ICMR. For analysing the challenges in the collection of convalescent plasma, the discharged patients were contacted telephonically. After applying eligibility criteria, the reasons of deferral were assessed. Data was collected and analysed. Results: The current prospective study was carried out during the period of 1st April 2020 to 15th May 2020. During this period, a total of 496 patients got discharged. After applying deferral criteria, 113 were eligible, out of which only 13 (11.5%) consented to come to donate plasma. Conclusion: In a global ongoing pandemic, the “Fear Factor” is a constraint and a major challenge to motivate and convince a COVID recovered patient for plasma donation. The challenge for the medical professionals is to motivate, convince and educate the potential donors and society about the likely benefits of COVID Convalescent Plasma.

Background: Patients undergoing hematopoietic stem cell transplantation (HSCT) are often referred for physical therapy (PT) to help improve their quality of life. However, to our knowledge there is no clear PT pathway to guide therapists and patients before, during, and after HSCT. Methods: A comprehensive literature review was carried out exploring the role and benefits of PT in HSCT patients. The current evidence was comlimented with recommendations and opinions from the experts in the field, which included PT's and hematology consultants from PTAGVHD and the EMBMT group. Result: A clear pathway and protocol as a working guide for rehabilitation professionals working with the HSCT patient's was developed. Conclusion: This paper not only reviews the current evidence on safe PT practice but also puts forward a protocol and pathway for HSCT rehabilitation, highlights the importance of individualized exercise intervention for HSCT patients, and outlines safe practice guidelines for the physical therapists working in this field. Keywords: Hematopoietic stem cell transplantation, Physical therapy, Rehabilitation

Despite effective factor replacement and various treatment schedules, there remain several challenges and unmet needs in the prophylactic treatment of hemophilia limiting its adoption and thereby posing an increased risk of spontaneous bleeding. In this regard, extended half-life (EHL) recombinant factor VIII (rFVIII) and factor IX (rFIX) products promise optimal prophylaxis by decreasing the dose frequency, increasing the compliance, and improving the quality of life without compromising safety and efficacy. EHL products might lead to higher trough levels without increasing infusion frequency, or could facilitate the ability to maintain trough levels while reducing infusion frequency. This paper aims to provide a comprehensive review of the rationale for developing EHL coagulation factors and their utility in the management of hemophilia, with special emphasis on optimal techniques for half-life extension and criteria for defining EHL coagulation factors, as well as indications, efficacy, and safety issues of the currently available EHL-rFVIII and EHL-rFIX products. Potential impacts of these factors on quality of life, health economics, and immune tolerance treatment will also be discussed alongside the challenges in pharmacokinetic-driven prophylaxis and difficulties in monitoring the EHL products with laboratory assays.Etkin faktör yerine koyma tedavisi ve değişik tedavi programlarına rağmen günümüzde hemofilinin profilaktik tedavisinde hala çözülmemiş sorunlar ve karşılanmamış gereksinimler vardır. Bu nedenle kanama riski ve kanamaya bağlı komplikasyonlar önemini korumaktadır. Bu bağlamda profilakside kullanılacak uzatılmış yarı ömürlü rekombinant faktör VIII ve faktör IX ürünleri tedavinin güvenlilik ve etkililiğinden ödün vermeksizin doz sıklığının azaltılması, hasta uyumunun artması ve yaşam kalitesinin düzelmesini sağlayarak optimal tedavi koşullarının oluşmasına yardımcı olabilir. Uzatılmış yarı ömürlü faktörler infüzyon sıklığını artırmadan daha yüksek çukur değerler ulaşılması veya mevcut çukur değerin daha seyrek infüzyonla idamesi konusunda önemli bir açılım sağlayabilir. Bu derlemede uzatılmış yarı ömürlü faktör konsantrelerinin geliştirilmesine neden gerek duyulduğu, hemofili tedavisindeki olası yerleri, faktör yarı ömrünü uzatmak için kullanılan teknikler ve mevcut uzatılmış yarı ömürlü faktör konsantrelerinin etkililik, güvenlilik ve endikasyonları ile ilişkili kapsamlı bilgi sunulacaktır. Ayrıca bu ürünlerin yaşam kalitesi ve sağlık ekonomisi üzerine etkileri, immün tolerans tedavisindeki yerleri, farmakokinetik temelli profilaside kullanımları ile laboratuvar izleminde karşılaşılan güçlükler tartışılacaktır.

Tanya R Riley, Treavor T RileyWingate University School of Pharmacy, Hendersonville, NC 28739, USACorrespondence: Tanya R RileyWingate University School of Pharmacy, 805 6th Avenue West; Suite 200, Hendersonville, NC 28739, USATel +1 828 697 0615Email ta.riley@wingate.eduAbstract: Sickle cell disease (SCD) is one of the most common inherited blood disorders globally. It is a grouping of autosomal recessive genetic disorders identified by a genetic mutation that replaces glutamic acid with valine at the sixth amino acid on the hemoglobin β-globin chain. Millions of people around the world live with a severe genotype of SCD that is often associated with occlusion of the microvasculature resulting in episodes of severe pain and multiple organ system dysfunction. These episodes, commonly categorized as vaso-occlusive crises (VOC), are a distinctive clinical presentation of SCD which represents the majority of SCD morbidity and associated hospitalizations. Though the complete process by which these crises occur is complex and not fully outlined, evidence reveals this process to be multifactorial and heterocellular. For nearly two decades, hydroxyurea was the only FDA-approved therapy for SCD. Evidence to date shows that hydroxyurea treatment significantly reduces the rate of VOC, hospitalizations, and mortality. Despite these benefits, adherence remains problematic due to a variety of adverse effects and interpatient variability connected with hydroxyurea therapy. Crizanlizumab, an adhesion inhibitor of sickled red blood cells, was recently granted breakthrough therapy designation. Results of a phase 2 study have reported a successful reduction in annual rates of vaso-occlusive crisis with a favorable safety profile. This paper reviews the available literature concerning crizanlizumab use in patients with SCD.Keywords: sickle cell, genotype, microvasculature, endothelium, vaso-occlusive crisis

Aderonke Anthonia Kayode, Abidemi Emmanuel Adeniyi, Roseline Oluwaseun Ogundokun, Simon Agaba OchigboDepartment of Computer Science, College of Applied Sciences, Landmark University, Omu-Aran, Kwara State, NigeriaBackground: Blood Bank record keeping has been carried out manually over the past decades using paper file management system which is slow for information retrieval and processing and also prone to errors in an emergency situation.Materials and methods: This research work solves the above-mentioned problem with the development of both web-based and Android-based blood bank information retrieval system. The web application is used by various blood banks system administrators to update their available blood inventory information and the mobile application which has the mobile search engine is used to search for blood supplies from the registered blood banks. Results and conclusion: The system also has a feature that allows registered blood banks to send a notification to registered blood donors on the application requesting for blood donation.Keywords: blood bank, web-based, Android-based, information, retrieval

Despite major scientific discoveries and novel therapies over the past four decades, the treatment outcomes of acute myeloid leukemia (AML), especially in the adult patient population remain dismal. In the past few years, an increasing number of targets such as CD33, CD123, CLL-1, CD47, CD70, and TIM3, have been developed for immunotherapy of AML. Among them, CLL-1 has attracted the researchers’ attention due to its high expression in AML while being absent in normal hematopoietic stem cell. Accumulating evidence have demonstrated CLL-1 is an ideal target for AML. In this paper, we will review the expression of CLL-1 on normal cells and AML, the value of CLL-1 in diagnosis and follow-up, and targeting CLL-1 therapy-based antibody and chimeric antigen receptor T cell therapy as well as providing an overview of CLL-1 as a target for AML.

An amendment to this paper has been published and can be accessed via the original article.

The incidence of venous thrombosis, mostly pulmonary embolism (PE), ranging from local immunothrombosis to central emboli, but also deep vein thrombosis (DVT) in people with coronavirus disease 2019 (COVID-19) is reported to be remarkably high. The relevance of better understanding, predicting, treating, and preventing COVID-19-associated venous thrombosis meets broad support, as can be concluded from the high number of research, review, and guideline papers that have been published on this topic. The Dutch COVID & Thrombosis Coalition (DCTC) is a multidisciplinary team involving a large number of Dutch experts in the broad area of venous thrombosis and hemostasis research, combined with experts on virology, critically ill patients, pulmonary diseases, and community medicine, across all university hospitals and many community hospitals in the Netherlands. Within the consortium, clinical data of at least 5000 admitted COVID-19-infected individuals are available, including substantial collections of biobanked materials in an estimated 3000 people. In addition to considerable experience in preclinical and clinical thrombosis research, the consortium embeds virology-hemostasis research models within unique biosafety facilities to address fundamental questions on the interaction of virus with epithelial and vascular cells, in relation to the coagulation and inflammatory system. The DCTC has initiated a comprehensive research program to answer many of the current questions on the pathophysiology and best anticoagulant treatment of COVID-19-associated thrombotic complications. The research program was funded by grants of the Netherlands Thrombosis Foundation and the Netherlands Organization for Health Research and Development. Here, we summarize the design and main aims of the research program.

Advanced diagnostic methods give an advantage for the identification of the abnormalities in myeloid malignancies. Various researchers have shown the potential importance of genetic tests both before the onset of the disease and during the remission. Large testing panels prevents false negative results in myeloid malignancies. But the important question is how the results of conventional cytogenetic and molecular cytogenetic techniques can be merged together with NGS technologies. In this paper, we drew an algorithm for evaluation of the myeloid malignancies. In order to evaluate genetic abnormalities, we performed cytogenetics, molecular cytogenetics and NGS testing in hematologic malignancies. In this study, we analyzed 100 patients who admitted to Medical Genetics Laboratory within different type of myeloid malignancies. We highlighted the possible diagnostic algorithm for cytogenetically normal cases. We applied NGS 141 gene panel for cytogenetically normal patients and we detected two or more pathogenic variations in 61 out of 100 patients (61%). The pathogenic variation detection rate of NGS varies in disease groups: AML were 85% and MDS were 23%. Here, we identified 24 novel variation out of total pathogenic variations in myeloid malignancies. A total 18 novel variation were identified in AML and 6 novel variation were identified in MDS. Despite of long turnaround time, conventional techniques are still golden standard for myeloid malignancies but sometimes cryptic gene fusions or complex abnormalities cannot be identified easily by conventional techniques. In these conditions, advanced technologies like NGS are highly recommended.

An amendment to this paper has been published and can be accessed via the original article.

An amendment to this paper has been published and can be accessed via the original article.

Pierpaolo Di Micco,1 Gualberto Gussoni,2 Filippo Pieralli,3 Mauro Campanini,4 Francesco Dentali,5 Andrea Fontanella1 1Department of Internal Medicine and Emergency Room, Fatebenefratelli Hospital of Naples, Naples, Italy; 2Centro Studi FADOI, Milan, Italy; 3Department of Medicine, Hospital Careggi, Florence, Italy; 4Department of Internal Medicine, Ospedale Maggiore, Novara, Italy; 5Department of Internal Medicine, University of Insubria, Varese, ItalyCorrespondence: Pierpaolo Di MiccoDepartment of Internal Medicine and Emergency Room, Fatebenefratelli Hospital of Naples, Naples, ItalyEmail pdimicco@libero.itAbstract: Factor XIII deficiency may be inherited or acquired. Inherited deficiency is associated with signs and symptoms of minor bleeding from a young age, and possible major bleeding complications, in particular during pregnancy. On the other hand, acquired factor XIII deficiency is usually associated with severe symptoms of major bleeding, in particular during surgery. In this paper, we report an interesting case of recurrent major bleeding with subsequent fatal bleeding in an adult man diagnosed with acquired factor XIII deficiency.Keywords: factor XIII deficiency, acquired haemophilia, blood disorders, bleeding, fatal bleeding

Primary cutaneous anaplastic large cell lymphoma is a CD-30 positive lymphoproliferative disorder with good prognosis, usually treated with radiation therapy and surgery. Head, neck, and extremities are the most frequently involved sites. In this paper, we describe an unusual case of oral localization, recurring after skin-involving radiotherapy, successfully treated with sixteen cycles of brentuximab vedotin. This could be a more effective approach with a less detrimental toll for treating these rare disorders.