Modification of deglycerolization procedure improves processing and post-thaw quality of cryopreserved sickle trait red cell concentrates.

Red blood cell (RBC) transfusion is a critical therapy for those with sickle cell disease (SCD). Alloimmunization is frequent for those with SCD and may limit the availability of matched RBC. Cryopreserved RBCs, from family members or donors with a similar RBC antigen profile could provide a viable alternative to avoid further alloimmunization and prevent hemolytic transfusion-related events. However, cryopreserved SCD and Sickle Cell trait (S-trait) donor RBC units suffer from reduced recovery following deglycerolization. This study proposes and tests a modified deglycerolization protocol using an automated cell processor to mitigate RBC loss. Six red cell concentrates (RCC) from donors with S-trait and six control RCCs were glycerolized, frozen (<-65 °C) and deglycerolized on the ACP 215 using modified parameters (decreased hypertonic solution flow rate (100 mL/min) and hypertonic equilibration delay (120 s), and increased NaCl dilution volumes (500 mL). Quality testing included: hematocrit (HCT), hemolysis, indices, extracellular potassium, morphology, osmotic fragility, osmotic gradient ektacytometry, hemoglobin (HGB), and recovery. Canadian standards (CS) indicate that acceptable deglycerolized units for transfusion require a HCT ≤0.80 L/L, HGB ≥35 g/unit, and hemolysis <0.8 % in 90 % of units tested. No significant differences in HGB or RBC recovery were observed between study groups. Significant differences between study groups were identified in osmotic fragility and osmotic gradient ektacytometry parameters. Of the 6 S-trait RCCs, 3/6 units were within the HCT, HGB and hemolysis thresholds set by the CS. The modified deglycerolization protocol provides a path for the routine cryopreservation of S-trait RBCs.

Acute care utilization in pediatric sickle cell disease and sickle cell trait in the USA: prevalence, temporal trends, and cost.

The objective of this study was to analyze acute care utilization of sickle cell disease (SCD) and sickle cell trait (SCT) in children and identify trends in emergency department (ED) visits and inpatient admissions over a 10-year period. This is a retrospective population-based study of SCD- and SCT-related ED visits and admissions from 2006 to 2015. Data were acquired from the Healthcare Cost and Utilization Project (HCUP), National Inpatient Sample (NIS), and National Emergency Department Sample (NEDS) database. Cost-to-charge and estimated professional fee ratios were applied to approximate costs. Over 80% of medical expenditure on HbSS is through ED-based admissions. There is a statistically significant increase from 2006 to 2015 in the direct hospital admissions associated with patients less than 18 years of age who have been diagnosed with SCT.Conclusion: Among patients less than 18 years of age with HbSS, inpatient admissions through the emergency department accounted for the largest medical expenditure of the SCD subtypes. What is Known: • There are currently no multi-year, nationwide analyses of acute care utilization in sickle cell disease and sickle cell trait (SCT) in the pediatric population. • SCT is more common than SCD, affecting 1.5% of all infants born in the USA. What is New: • Comprehensive annual costs of acute care utilization of patients less than 18 years of age with SCD and SCT in the USA which includes aggregated demographical patient care data and to illustrate temporal trends of acute care utilization in children less than 18 years of age with SCD and SCT • Among patients less than 18 years of age with HbSS, inpatient admissions through the emergency department accounted for the largest medical expenditure of the sickle cell disease subtypes.

Increasing Wellness Through Physical Activity in Children With Chronic Disease and Disability.

Children with chronic medical conditions face many challenges when considering sport participation. Compared with their healthy counterparts, they are often discouraged from physical activity or sports participation because of real or perceived limitations imposed by their condition. Prescribed exercise should be based on the demands of the sport, the effect of the disease on performance, and the potential for exercise-induced acute or chronic worsening of the illness or disability. This article will focus on several examples of chronic medical conditions and the clinician's role in providing advice about sport participation.

Top 10 Research Questions Related to Preventing Sudden Death in Sport and Physical Activity.

Participation in organized sport and recreational activities presents an innate risk for serious morbidity and mortality. Although death during sport or physical activity has many causes, advancements in sports medicine and evidence-based standards of care have allowed clinicians to prevent, recognize, and treat potentially fatal injuries more effectively. With the continual progress of research and technology, current standards of care are evolving to enhance patient outcomes. In this article, we provided 10 key questions related to the leading causes and treatment of sudden death in sport and physical activity, where future research will support safer participation for athletes and recreational enthusiasts. The current evidence indicates that most deaths can be avoided when proper strategies are in place to prevent occurrence or provide optimal care.

Sickle Cell Trait Increases Red Blood Cell Storage Hemolysis and Post-Transfusion Clearance in Mice.

BACKGROUND: Transfusion of blood at the limits of approved storage time is associated with lower red blood cell (RBC) post-transfusion recovery and hemolysis, which increases plasma cell-free hemoglobin and iron, proposed to induce endothelial dysfunction and impair host defense. There is noted variability among donors in the intrinsic rate of storage changes and RBC post-transfusion recovery, yet genetic determinants that modulate this process are unclear. METHODS: We explore RBC storage stability and post-transfusion recovery in murine models of allogeneic and xenogeneic transfusion using blood from humanized transgenic sickle cell hemizygous mice (Hbatm1PazHbbtm1TowTg(HBA-HBBs)41Paz/J) and human donors with a common genetic mutation sickle cell trait (HbAS). FINDINGS: Human and transgenic HbAS RBCs demonstrate accelerated storage time-dependent hemolysis and reduced post-transfusion recovery in mice. The rapid post-transfusion clearance of stored HbAS RBC is unrelated to macrophage-mediated uptake or intravascular hemolysis, but by enhanced sequestration in the spleen, kidney and liver. HbAS RBCs are intrinsically different from HbAA RBCs, with reduced membrane deformability as cells age in cold storage, leading to accelerated clearance of transfused HbAS RBCs by entrapment in organ microcirculation. INTERPRETATION: The common genetic variant HbAS enhances RBC storage dysfunction and raises provocative questions about the use of HbAS RBCs at the limits of approved storage.

Challenging Return to Play Decisions: Heat Stroke, Exertional Rhabdomyolysis, and Exertional Collapse Associated With Sickle Cell Trait.

CONTEXT: Sports medicine providers frequently return athletes to play after sports-related injuries and conditions. Many of these conditions have guidelines or medical evidence to guide the decision-making process. Occasionally, however, sports medicine providers are challenged with complex medical conditions for which there is little evidence-based guidance and physicians are instructed to individualize treatment; included in this group of conditions are exertional heat stroke (EHS), exertional rhabdomyolysis (ER), and exertional collapse associated with sickle cell trait (ECAST). EVIDENCE ACQUISITION: The MEDLINE (2000-2015) database was searched using the following search terms: exertional heat stroke, exertional rhabdomyolysis, and exertional collapse associated with sickle cell trait. References from consensus statements, review articles, and book chapters were also utilized. STUDY DESIGN: Clinical review. LEVEL OF EVIDENCE: Level 4. RESULTS: These entities are unique in that they may cause organ system damage capable of leading to short- or long-term detriments to physical activity and may not lend to complete recovery, potentially putting the athlete at risk with premature return to play. CONCLUSION: With a better understanding of the pathophysiology of EHS, ER, and ECAST and the factors associated with recovery, better decisions regarding return to play may be made.

Out with the bad and in with the good; red cell exchange, white cell reduction, and platelet reduction.

Automated techniques for red cell [red blood cell (RBC)] exchange or depletion of malignant cells from the peripheral blood have allowed patients with life-threatening conditions to survive long enough to receive definitive treatment. Examples of such conditions include acute chest syndrome in sickle cell disease (SCD) or acute respiratory insufficiency due to leukostasis in acute leukemia. Conversely, other patients with SCD undergo RBC exchanges on a chronic basis to maintain a reasonable quality of life and prevent another stroke. In this review, we will discuss the techniques as well as indications for RBC exchange, leukocytapheresis, and thrombocytapheresis. To illustrate the uses of these therapeutic apheresis procedures, the authors included a summary of the most common diagnoses that comprise their use.

Recommendations for the management of sickle cell disease in South Africa.

The spectrum of sickle cell disease (SCD) encompasses a heterogeneous group of disorders that include: (I) homozygous SCD (HbSS), also referred to as sickle cell anaemia; (ii) heterozygous SCD (HbAS), also referred to as sickle cell trait; and (iii) compound heterozygous states such as HbSC disease, HbSß thalassaemia, etc. Homozygous or compound heterozygous SCD patients manifest with clinical disease of varying severity that is influenced by biological and environmental factors, whereas subject with sickle cell trait are largely asymptomatic. SCD is characterized by vaso-occlusive episodes that result in tissue ischaemia and pain in the affected region. Repeated infarctive episodes cause organ damage and may eventually lead to organ failure. For effective management, regular follow-up with support from a multidisciplinary healthcare team is necessary. The chronic nature of the disease, the steady increase in patient numbers, and relapsing acute episodes have cost implications that are likely to impact on provincial and national health budgets. Limited resources mandate local management protocols for the purposes of consistency and standardisation, which could also facilitate sharing of resources between centres for maximal utility. These recommendations have been developed for the South African setting, and it is intended to update them regularly to meet new demands and challenges.

Framing the research agenda for sickle cell trait: building on the current understanding of clinical events and their potential implications.

Sickle Cell Trait (HbAS), the heterozygous state for the sickle hemoglobin beta globin gene is carried by as many as 100 million individuals including up to 25% of the population in some regions of the world (World Health Organization, Provisional agenda item 4.8, EB117/34 (22 December 2005) or World Health Organization, Provisional agenda item 11.4 (24 April 2006)). Persons with HbAS have some resistance to falciparum malaria infection in early childhood (Piel FB, Patil AP, Howes RE, et al., Nat Commun 2010;1104:1-7 and Aidoo M, Terlouw DJ, Kolczak M, et al., Lancet 2002;359:1311-1312) and as a result individuals with HbAS living in malarial endemic regions of Africa have a survival advantage over individuals with HbAA. Reports from the US emphasize possible health risks for individuals with HbAS including increased incidence of renal failure and malignancy, thromboembolic disorders, splenic infarction as a high altitude complication, and exercise-related sudden death. The National Heart, Lung, and Blood Institute, National Institutes of Health convened a workshop in Bethesda, Maryland on June 3-4, 2010, Framing the Research Agenda for Sickle Cell Trait, to review the clinical manifestations of HbAS, discuss the exercise-related sudden death reports in HbAS, and examine the public health, societal, and ethical implications of policies regarding HbAS. The goal of the workshop was to identify potential research questions to address knowledge gaps.

Interação entre traço falciforme e alfa-talassemia: relato de um caso no noroeste de Paraná / Interaction between sickle cell trait and alpha-thalassemia: a case report in the northwest Paraná

O traço falciforme associado à alfa-talassemia (AS/α-talassemia) é uma característica rara na população do sul do Brasil. Em função deste e de outros motivos, casos dessa interação são confundidos e muitas vezes subdiagnosticados como sendo de anemia ferropriva, o que pode levar pacientes a tratamentos desnecessários e, muitas vezes prejudiciais à sua saúde. Este trabalho relata o caso de uma paciente de 80 anos de idade que, após participar de um estudo populacional sobre incidência de hemoglobinopatias, descobriu ser portadora da interação AS/α-talassemia. Até então vinha recebendo tratamento para anemia ferropriva, apesar de não apresentar melhora. Este trabalho discute ainda como os índices hematimétricos, associados aos achados eletroforéticos, contribuíram para um diagnóstico diferencial da interação AS/α-talassemia, o que pode auxiliar médicos e profissionais da saúde a um diagnóstico mais preciso, visando à melhoria da qualidade de vida do paciente e, consequentemente, a diminuição da incidência destas doenças genéticas na população.

Sickle cell trait, associated to alpha-thalassemia (AS/α-talassemia), is a rare characteristic in the population living in the South of Brazil. Because of such a rare condition and other reasons, cases of that interaction are confusing and most of the times sub-diagnosed as iron deficiency anemia, thus submitting the disease carrier to unnecessary treatments which, most of the time, are harmful to the patient’s health. The present study reports the case of an 80-year-old patient, who after taking part in a study on the incidence of hemoglobinopathies on population, discovered to carry the interaction AS/α-thalassemia. Up to then the patient had been submitted to treatments to control iron deficiency anemia, although not presenting any improvement. Moreover, the present study discusses how hematimeter indexes, associated to electrophoretic findings, have contributed for a differential diagnosis of AS/α-talassemia interaction, what may aid physicians and health professionals to obtain a more precise diagnosis, aiming at improving the patient’s life-quality, and consequently, leading to a decrease in the incidence of such genetic diseases in the population.

Red blood cells from donors with sickle cell trait: a safety issue for transfusion?

Sickle cell trait (SCT) affects approximately 8% of the population in Martinique (FWI) and about the same rate is found among the African Americans. In several regions of tropical Africa, up to 40% of individuals are also affected. SCT has been characterized as a benign condition and patients are currently asymptomatic or run a benign course. However, life-threatening complications may occur. SCT can be detected in patients hospitalized for various complaints, and SCT likely causes serious morbidity and mortality in some people. Moreover, these clinical observations have been supported by several in vitro studies in which haemoglobin AS red cells showed abnormalities of their filterability. These problems are revisited with the implementation of universal leucoreduction in several countries. The question of the screening of all blood donors for SCT and the use of their red blood cells (RBCs) has yet to be resolved.

Umbilical cord blood transplantation: newer trends.

During last ten years, over 4000 umbilical cord blood transplantations have been performed worldwide. The interest in this modality of transplantation has been growing as this provides easy access to an alternative source of stem cells for treating cancer and serious genetic disorders with otherwise fatal outcome or immense morbidity. Umbilical cord blood is a commonly discarded source of useful stem cells. The outcome of transplantation using cells from this source in children mirrors the results of unrelated donor transplantation and hence the procedure is widely accepted by paediatric transplant community. Results are, however, hampered in adults due to low cell dose. Newer techniques, such as pooled or sequential cord blood transplantation, may help to increase progenitor cell numbers and improve immune reconstitution. In near future, non-haematopoietic uses will make this even more exiting area. In this write-up, we will review this treatment including cord blood banking issues and the ethical concerns. We will discuss both paediatric and adult transplantations including certain new indications.