Iron overload across the spectrum of non-transfusion-dependent thalassaemias: role of erythropoiesis, splenectomy and transfusions

Non-transfusion-dependent thalassaemias (NTDT) encompass a spectrum of anaemias rarely requiring blood transfusions. Increased iron absorption, driven by hepcidin suppression secondary to erythron expansion, initially causes intrahepatic iron overload. We examined iron metabolism biomarkers in 166 NTDT patients with β thalassaemia intermedia (n = 95), haemoglobin (Hb) E/β thalassaemia (n = 49) and Hb H syndromes (n = 22). Liver iron concentration (LIC), serum ferritin (SF), transferrin saturation (TfSat) and non-transferrin-bound iron (NTBI) were elevated and correlated across diagnostic subgroups. NTBI correlated with soluble transferrin receptor (sTfR), labile plasma iron (LPI) and nucleated red blood cells (NRBCs), with elevations generally confined to previously transfused patients. Splenectomised patients had higher NTBI, TfSat, NRBCs and SF relative to LIC, than non-splenectomised patients. LPI elevations were confined to patients with saturated transferrin. Erythron expansion biomarkers (sTfR, growth differentiation factor-15, NRBCs) correlated with each other and with iron overload biomarkers, particularly in Hb H patients. Plasma hepcidin was similar across subgroups, increased with >20 prior transfusions, and correlated inversely with TfSat, NTBI, LPI and NRBCs. Hepcidin/SF ratios were low, consistent with hepcidin suppression relative to iron overload. Increased NTBI and, by implication, risk of extra-hepatic iron distribution are more likely in previously transfused, splenectomised and iron-overloaded NTDT patients with TfSat >70%

Defining the phenotypes of sickle cell disease.

The sickle cell gene is pleiotropic in nature. Although it is a single gene mutation, it has multiple phenotypic expressions that constitute the complications of sickle cell disease. The frequency and severity of these complications vary considerably both latitudinally in patients and longitudinally in the same patient over time. Thus, complications that occur in childhood may disappear, persist or get worse with age. Dactylitis and stroke, for example, occur mostly in childhood, whereas leg ulcers and renal failure typically occur in adults. It is essential that the phenotypic manifestations of sickle cell disease be defined accurately so that communication among providers and researchers facilitates the implementation of appropriate and cost-effective diagnostic and therapeutic modalities. The aim of this review is to define the complications that are specific to sickle cell disease based on available evidence in the literature and the experience of hematologists in this field

Pulmonary hypertension in hemolytic anemias

Pulmonary hypertension (PH) has been reported with nearly all forms of the inherited as well as the acquired hemolytic anemias. Recent research investigating the pathophysiology of PH in sickle cell disease and thalassemia has helped elucidate the central role of hemolysis-mediated endothelial dysfunction in the development of PH in these populations. Although the most appropriate treatment of PH in patients with hemolytic anemia is not clearly defined, the associated significant increased risk of death underscores the need for randomized clinical trials in this area

Definitions of the phenotypic manifestations of sickle cell disease.

Sickle cell disease (SCD) is a pleiotropic genetic disorder of hemoglobin that has profound multiorgan effects. The low prevalence of SCD ( approximately 100,000/US) has limited progress in clinical, basic, and translational research. Lack of a large, readily accessible population for clinical studies has contributed to the absence of standard definitions and diagnostic criteria for the numerous complications of SCD and inadequate understanding of SCD pathophysiology. In 2005, the Comprehensive Sickle Cell Centers initiated a project to establish consensus definitions of the most frequently occurring complications. A group of clinicians and scientists with extensive expertise in research and treatment of SCD gathered to identify and categorize the most common complications. From this group, a formal writing team was formed that further reviewed the literature, sought specialist input, and produced definitions in a standard format. This article provides an overview of the process and describes 12 body system categories and the most prevalent or severe complications within these categories. A detailed Appendix provides standardized definitions for all complications identified within each system. This report proposes use of these definitions for studies of SCD complications, so future studies can be comparably robust and treatment efficacy measured. Use of these definitions will support greater accuracy in genotype-phenotype studies, thereby achieving a better understanding of SCD pathophysiology. This should nevertheless be viewed as a dynamic rather than final document; phenotype descriptions should be reevaluated and revised periodically to provide the most current standard definitions as etiologic factors are better understood, and new diagnostic options are developed

Coordination chemistry and biology of chelators for the treatment of iron overload disorders

Treatment of the medical condition generally referred to as iron overload through the delivery of chelators has recently received a major boost. In 2005 Novartis gained FDA approval for the drug deferasirox, which may be taken orally. Until this time most patients with Fe overload have had to endure long periods of subcutaneous infusions of the orally ineffective drug desferrioxamine (desferal) which has led to major problems with patient compliance. An effective Fe chelator must possess a number of properties for it to be able to complex Fe in vivo and be excreted intact. This Perspective will provide an overview of the current state of chelators for Fe overload; both those currently approved and those undergoing preclinical development

OS LUSÍADAS E O MARIALVISMO NA ESCOLA NOVA DE SALAZAR

The political regime that was known in Portugal as Estado Novo has used a discourse that was based on moral, religious and civic values. This paper wants to show how this discourse, that we want to characterize as potentially “marialva”, has influenced the adaptations pieces of the camonian epic poem for children's reading, which was held in the schools of that period. For this, we want to confront one of these adapted pieces with some of the elements of the Salazar’s policy, and these with what Jose Cardoso Pires points as “marialvismo”.O regime político português que ficou conhecido como Estado Novo teve por característica um discurso sedimentado em valores morais, religiosos e cívicos. O presente trabalho busca mostrar de que forma tal discurso, que pretendemos caracterizar como potencialmente marialva, influenciou a adaptação do poema épico camoniano para a leitura infanto-juvenil, realizada nas escolas daquele período. Para tanto, confrontaremos uma dessas obras adaptadas com alguns dos elementos da política de Salazar, e estes com o que José Cardoso Pires aponta como marialvismo

Neuropsychological Dysfunction and Neuroimaging Abnormalities in Neurologically Intact Adults With Sickle Cell Anemia

Sickle cell anemia (SCA) is a chronic illness causing progressive deterioration in quality of life. Brain dysfunction may be the most important and least studied problem affecting individuals with this disease

Outcome of children with sickle cell disease admitted to intensive care:a single institution experience

We retrospectively audited children with sickle cell disease (SCD) admitted to paediatric intensive care (PICU) at King's College Hospital between January 2000 and December 2008. Forty-six children with SCD were admitted, on 49 separate occasions. Ages ranged from 4 months to 15 years (median 7 6 years). Three children died in PICU, however two presented to hospital in cardiorespiratory arrest; overall mortality was 6%. The most common reason for admission was acute chest syndrome (43%). 88% of admissions required blood transfusion, of which 74% had exchange blood transfusions. The mortality among children with SCD admitted to PICU is low