Classical infratentorial superficial siderosis of the central nervous system: pathophysiology, clinical features and management

The term superficial siderosis (SS) is derived from the Greek word 'sideros', meaning iron. It includes two subtypes, distinguished by their anatomical distribution, causes and clinical features: 'classical' infratentorial SS (iSS, which sometimes also affects supratentorial regions) and cortical SS (cSS, which affects only supratentorial regions). This paper considers iSS, a potentially disabling disorder usually associated with very slow persistent or intermittent subarachnoid bleeding from a dural defect, and characterised by progressive hearing and vestibular impairment, ataxia, myelopathy and cognitive dysfunction. The causal dural defect-most often spinal but sometimes in the posterior fossa-typically follows trauma or neurosurgery occurring decades before diagnosis. Increasing recognition of iSS with paramagnetic-sensitive MRI is leading to an unmet clinical need. Given the diagnostic challenges and complex neurological impairments in iSS, we have developed a multidisciplinary approach involving key teams. We discuss pathophysiology, diagnosis and management of iSS, including a proposed clinical care pathway

The example of the UK SHOT haemovigilance system

SHOT (Serious Hazards of Transfusion scheme) is the UK’s National confidential haemovigilance system, and was set up in 1996. It is an independent, confidential, professionally led haemovigilance scheme. Initially the reporting was voluntary but now required by several professional bodies. SHOT publishes annual reports with recommendations and circulates to all relevant organizations including the 4 UK Blood services, Departments of Health in England, Wales, Scotland and Northern Ireland, all relevant professional bodies and reporting hospitals. Over the 17 years of reporting, the evidence gathered has prompted changes in transfusion practice from the selection and management of donors to changes in hospital practice, better education and training. Acute transfusion reactions and transfusion-associated circulatory overload carry the highest risk for morbidity and death. Greatest risk to patients remain errors in the process at the point of blood sampling, in the laboratory and at bedside administration. SHOT’s objectives are to use findings to improve standards of hospital transfusion practice, to educate users on transfusion hazards and prevention, to aid production of clinical guidelines in blood transfusion and to inform national policy on transfusion safety. MHRA is the UK competent authority to which serious adverse reactions and events have to be reported annually. Overall the most common adverse incidents are caused by errors, resulting in the transfusion of an incorrect component or one that does not meet the specific requirements of the patient (e.g. not irradiated or not appropriately antigen matched). TACO (transfusion associated circulatory overload) accounts for most deaths and major morbidity reported to SHOT but is overall underreported. Transfusions are not always given appropriately. This may be due to wrong haemoglobin results, failure to assess patients appropriately, or avoidable use of emergency O RhD negative units because of poor communication or planning. Review of cases of haemolytic transfusion reactions (HTR) shows that they are observed mainly in Sickle Cell Disease patients. HTR are associated with major morbidity (10/16 cases in sickle cell patients over 3 years) and death (a child in 2010). SCD patients are at particular risk of alloimmunization and this can be reduced by red cell phenotyping prior to the first transfusion followed by routine matching for at least the Rh and Kell groups. SHOT output data led over the time to the development of strategies to improve transfusion safety such as the implementation of guidelines for improving practice, implementation of the National Comparative Audit of Blood Transfusion programme, the publication of the Better blood transfusion initiatives and the establishment of The UK transfusion laboratory collaborative

2021 Thalassaemia International Federation Guidelines for the Management of Transfusion-dependent Thalassemia

Beta-thalassemia and particularly its transfusion-dependent form (TDT) is a demanding clinical condition, requiring life-long care and follow-up, ideally in specialized centers and by multidisciplinary teams of experts. Despite the significant progress in TDT diagnosis and treatment over the past decades that has dramatically improved patients’ prognosis, its management remains challenging. On one hand, diagnostic and therapeutic advances are not equally applied to all patients across the world, particularly in several high-prevalence eastern regions. On the other, healthcare systems in low-prevalence western countries that have recently received large numbers of migrant thalassemia patients, were not ready to address patients’ special needs. Thalassaemia International Federation (TIF), a global patient-driven umbrella federation with 232 member-associations in 62 countries, strives for equal access to quality care for all patients suffering from thalassemia or other hemoglobinopathies in every part of the world by promoting education, research, awareness, and advocacy. One of TIF’s main actions is the development and dissemination of clinical practice guidelines for the management of these patients. In 2021, the fourth edition of TIF’s guidelines for the management of TDT was published. The full text provides detailed information on the management of TDT patients and the clinical presentation, pathophysiology, diagnostic approach, and treatment of disease complications or other clinical entities that may occur in these patients, while also covering relevant psychosocial and organizational issues. The present document is a summary of the 2021 TIF guidelines for TDT that focuses mainly on clinical practice issues and recommendations

Genetic and clinical heterogeneity in thirteen new cases with aceruloplasminemia. Atypical anemia as a clue for an early diagnosis

Aceruloplasminemia is a rare autosomal recessive genetic disease characterized by mild microcytic anemia, diabetes, retinopathy, liver disease, and progressive neurological symptoms due to iron accumulation in pancreas, retina, liver, and brain. The disease is caused by mutations in the Ceruloplasmin (CP) gene that produce a strong reduction or absence of ceruloplasmin ferroxidase activity, leading to an impairment of iron metabolism. Most patients described so far are from Japan. Prompt diagnosis and therapy are crucial to prevent neurological complications since, once established, they are usually irreversible. Here, we describe the largest series of non-Japanese patients with aceruloplasminemia published so far, including 13 individuals from 11 families carrying 13 mutations in the CP gene (7 missense, 3 frameshifts, and 3 splicing mutations), 10 of which are novel. All missense mutations were studied by computational modeling. Clinical manifestations were heterogeneous, but anemia, often but not necessarily microcytic, was frequently the earliest one. This study confirms the clinical and genetic heterogeneity of aceruloplasminemia, a disease expected to be increasingly diagnosed in the Next-Generation Sequencing (NGS) era. Unexplained anemia with low transferrin saturation and high ferritin levels without inflammation should prompt the suspicion of aceruloplasminemia, which can be easily confirmed by low serum ceruloplasmin levels. Collaborative joint e_orts are needed to better understand the pathophysiology of this potentially disabling disease