Telomere biology disorders: from dyskeratosis congenita and beyond.

Defective telomerase function or telomere maintenance causes genomic instability. Alterations in telomere length and/or attrition are the primary features of rare diseases known as telomere biology disorders or telomeropathies. Recent advances in the molecular basis of these disorders and cutting-edge methods assessing telomere length have increased our understanding of this topic. Multiorgan manifestations and different phenotypes have been reported even in carriers within the same family. In this context, apart from dyskeratosis congenita, disorders formerly considered idiopathic (i.e. pulmonary fibrosis, liver cirrhosis) frequently correlate with underlying defective telomere maintenance mechanisms. Moreover, these patients are prone to developing specific cancer types and exhibit exceptional sensitivity and toxicity in standard chemotherapy regimens. The current review describes the diverse spectrum of clinical manifestations of telomere biology disorders in pediatric and adult patients, their correlation with pathogenic variants, and considerations during their management to increase awareness and improve a multidisciplinary approach.

Hematological manifestation of Pediatric Systemic Lupus Erythematosus (SLE) - A single centered cross-sectional study.

Introduction: Systemic lupus erythematosus (SLE), the commonest type of lupus, is an autoimmune multisystemic disorder that can affect any organ system of the body, especially blood vessels and connective tissues, causing widespread inflammation. Pediatric onset of SLE is a rare condition with more hematological involvement. Aim: This study was undertaken to observe various hematological abnormalities and their association with various autoantibodies present in pediatric SLE in Eastern India. Methodology: It was a single-centered, cross-sectional, observational, hospital-based study conducted in the Department of Pediatric Medicine in collaboration with the Department of Rheumatology in IPGME and R and SSKM Hospital, Kolkata. The duration of the study was 1.5 years, and a total of 30 children up to 12 years of age of either gender were enrolled. Study participants were evaluated for various parameters like demographic, hematological (anemia, neutropenia, leucopenia, lymphopenia, and thrombocytopenia), biochemical (CRP, Lactate dehydrogenase (LDH), and bilirubin), autoantibodies (anti-dsDNA, anti-Ro 52, and anti-Ribonucleoprotein [RNP]), and SLE related pathologies (Cutaneous, nephritis, serositis). Results: In the present study, most of the participants had arthritis, muscle pain (86.66%), and hematological involvement (80%). Among cytopenias, anemia was the commonest. dsDNA autoantibody was positive in most of the patients (83%), and about one-third suffered from autoimmune hemolytic anemia (AIHA). No association was observed between autoantibodies and various hematological manifestations. Conclusion: It can be concluded from the present study that anemia is the most common cytopenia in pediatric SLE, but there is no association between autoantibodies and these cytopenias. However, study on larger population may give better results.

Combined Presentation of Acute Confusion and Severe Pancytopenia in Vitamin B12 Deficiency.

Vitamin B12 deficiency is more prevalent in the elderly and can develop as a result of malnutrition, malabsorption, chronic alcoholism, and chronic use of common medications (e.g. metformin, PPI, methotrexate) along with other causes. A wide spectrum of hematological and neuropsychiatric manifestations exist with the most common being Megaloblastic anemia and subacute combined degeneration, respectively. The mechanisms leading to the manifestations specific to these two organ systems are thought to be different. The severity of neuropsychiatric presentation is reported to be inversely proportional to that of hematological presentation, thus making it uncommon for both to be readily apparent simultaneously. Regardless of the severity of the clinical presentation, a good response to vitamin B12 replacement therapy is reported despite the lack of guidelines regarding dosing, frequency, or duration of treatment needed to note improvement in manifestations. The aim of this report is to increase the provider's knowledge that a severe combined hematological and neuropsychiatry manifestation can co-exist and report the management used for recovery.

Diferentes formas de presentación de la anemia megaloblástica en el lactante / Different forms of presentation of megaloblastic anemia in the infant

Introducción: La anemia megalobástica es un trastorno madurativo de los precursores eritroides y mieloides causado por déficit de vitamina B12, ácido fólico, o ambos. Es poco común en la infancia y su prevalencia se desconoce por ser una enfermedad poco frecuente. Objetivo: Describir diferentes formas de presentación de la anemia megaloblástica en el lactante. Presentación de casos: Se presentan dos casos de lactantes, en el caso 1 la madre tuvo una alimentación precaria durante el embarazo y la lactancia, prolongó la lactancia materna exclusiva más de 6 meses. La paciente comenzó a perder las habilidades ganadas en el desarrollo psicomotor y presentó trastornos neurológicos graves, por lo que se consideró que se trataba de una enfermedad progresiva del sistema nervioso central. En el caso 2, en el que se prolongó la lactancia materna exclusiva, apareció trombocitopenia, por lo que se sospechó una enfermedad hematológica maligna. Resultados: En ambos casos después de realizar diversas pruebas para descartar enfermedades neurológicas (caso 1) y enfermedades hematológicas (caso 2) se diagnosticó anemia megaloblástica por déficit de vitamina B12 por disminución en la ingesta y una reserva limítrofe en la madre que lacta. En ambos casos los síntomas desaparecieron con el tratamiento vitamínico sustitutivo. Conclusiones: En el lactante la anemia megaloblástica se puede presentar de diferentes formas clínicas a pesar de tener la misma causa, un déficit en la ingesta y una reserva escasa de la madre durante el embarazo y lactancia(AU)

Introduction: Megaloblastic anemia is a maturing disorder of the erythroid and myeloid precursors caused by deficiency of vitamin B12, folic acid, or both. It is uncommon in childhood and its prevalence is unknown because it is a rare disease. Objective: To describe different forms of presentation of megaloblastic anemia in infants. Presentation of cases: Two cases of infants are presented, in case 1 the mother had a precarious diet during pregnancy and lactation, and prolonged exclusive breastfeeding more than 6 months. The patient began to lose the skills gained in psychomotor development and presented severe neurological disorders, so it was considered that it was a progressive disease of the central nervous system. In case 2, in which exclusive breastfeeding was prolonged, thrombocytopenia appeared, so a malignant hematological disease was suspected. Results: In both cases, after performing various tests to rule out neurological diseases (case 1) and hematological diseases (case 2), megaloblastic anemia was diagnosed due to vitamin B12 deficiency due to a decrease in intake and a borderline reserve in the breastfeeding mother. In both cases the symptoms disappeared with vitamin replacement therapy. Conclusions: In the infant, megaloblastic anemia can occur in different clinical ways despite having the same cause, a deficit in intake and a low reserve of the mother during pregnancy and lactation(AU)

A Practical Perspective of the Hematologic Manifestations of Systemic Lupus Erythematosus.

Systemic lupus erythematosus (SLE) is a chronic inflammatory disease with an unknown etiology that can affect any organ or system of the human body. Hematological, renal, or central nervous system manifestations in these patients result in great morbidity because high doses of glucocorticoids, cytotoxic medications, or biological drugs are required to control these manifestations. It is noteworthy that hematological involvement predominates during the first years of the disease and tends to last over time, with the premise that it may be the initial manifestation of the disease. Clear examples of this are the cases of hemolytic anemia and immune thrombocytopenia that can be initially classified as idiopathic or primary to be later classified as secondary when associated with infections, medications, neoplasms, or autoimmune diseases. The spectrum of hematologic manifestations in SLE is very broad, including lymphopenia, anemia, thrombocytopenia, or pancytopenia. In some cases, lymphadenopathy and splenomegaly are also identified. The vast majority of these manifestations denote high disease activity. However, many of these alterations have a multifactorial cause that must be taken into account to adopt a more complete therapeutic approach. The objective of this review is to characterize in detail the hematological manifestations of SLE to offer clinicians a practical vision of its diagnosis and treatment.

Hematological Manifestations of COVID-19 and Their Prognostic Significance in an Intensive Care Unit: A Cross-Sectional Study.

Introduction Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) started as a pathology chiefly affecting the lower respiratory tract. It was first encountered in Wuhan, China. As an infection with an unknown etiology, it was extensively studied in order to establish its profile with respect to the probable manifestations and required medical management. The hematological profile of a patient typically affected with coronavirus disease 2019 (COVID-19) showed lymphopenia with an altered neutrophil-lymphocyte ratio, raised inflammatory markers like D-dimer, interleukin 6 (IL-6), C-reactive protein (CRP), lactate dehydrogenase, and serum ferritin. The prognostic significance of these markers has been studied in this cross-sectional study. Patients and methods Data were collected from consecutive subjects admitted in the intensive care unit of Acharya Vinobha Bhave Rural Hospital, Sawangi Meghe, Wardha, who were aged more than 16 years and were later confirmed to be positive for COVID-19 through throat/nasal swab (rapid antigen test/reverse transcription-polymerase chain reaction (RT-PCR)). Written informed consent (by signature or thumbprint) was obtained from all participants. Statistical analysis was done by using descriptive and inferential statistics with the help of the chi-square test and z-test for the difference between two means. The software used in the analysis was SPSS 27.0 (IBM Corp., Armonk, NY) and GraphPad Prism 7.0 (GraphPad Software, San Diego, CA). P<0.05 was considered as the level of significance. Results A total of 200 patients were studied. Fifty-nine point five percent (59.5%) of those who succumbed were over 50 years of age and a significant number (23.5 %) had comorbidities like diabetes mellitus, hypertension, and chronic kidney disease. There was a significant positive correlation between the mortality rate and mean platelet volume (P=0.001), neutrophil-lymphocyte ratio (P=0.001), raised D-dimer (P=0.006), serum ferritin (P=0.0001), lactate dehydrogenase (P=0.0001), and C-reactive protein (P=0.0001). Conclusion The analysis of the data collected highlights the correlation between the studied hematological manifestations of COVID 19 and their association with the severity of the disease.

Splenic Infarction Induced by Dengue Hemorrhagic Fever: A Rare Presentation.

Haematological and vascular features of dengue virus infection are common and vary from tiny skin haemorrhages to significant bleeding such as epistaxis, gastrointestinal bleeding and hematuria. Spontaneous splenic rupture has also been reported as an atypical manifestation in dengue fever. We report a case of splenic infarction in a 35-year-old man who presented with fever, vomiting, diffuse abdominal pain and distention, diarrhoea, hematuria, headache, back pain, hypotension, pleural effusion and ascites. Laboratory evaluation confirmed the diagnosis of dengue hemorrhagic fever, and abdominal imaging revealed splenic infarction. He required intensive care, responded well to inotropic support and remarkably improved.

Role of hematological parameters in the stratification of COVID-19 disease severity.

OBJECTIVE: COVID-19 virus involves respiratory as well as other body systems including cardiovascular, gastrointestinal, neurological, immunological and hematopoietic system. Patient of covid-19 pneumonia presents with wide range of hemostatic abnormalities. These hemostatic abnormalities in COVID-19 are related with disease progression, severity and mortality. The Objective of our study is to evaluate the role of hematological parameters in determination of COVID-19 disease severity. MATERIAL AND METHOD: This was a retrospective study, conducted in Department of Pathology and Department of medicine, FMH college of Medicine and Dentistry from May 2020 to July 2020. Total of 101, confirmed cases of covid-19 disease, both genders between 17 and 75-year age were included. Hematological parameters were compared in mild, moderate, severe and critical disease group. Continuous variables were analyzed by using non parametric, Kruskal Wallis test while categorical variables were analyzed by chi-square test. RESULTS: Out of 101 patients, 20.8%, 51.8%,19.8% and 7.9% were in mild, moderate, severe and critical group respectively. Median (IQR) values of WBCs (p-value 0.004), ANC (p-value 0.002), NLR (p-value 0.001), D-dimer level (p-value 0.001), ferritin (0.0001), LDH (0.0001) were significantly increased in patients with critical disease. Median (IQR) values of APTT (p-value 0.003) and CRP (p- value 0.0001) were suggestively higher in patients with severe disease. Other parameters like Hemoglobin, MCV, HCT, ALC, Platelet count, prothrombin time did not show statistically significant association with severity of disease. CONCLUSION: The study concluded that Leukocytosis, neutrophilia, elevated Neutrophil to lymphocyte ratio, APTT, D-dimer, LDH and serum ferritin and CRP are associated with severity of covid-19 disease.

Hematological manifestations of SARS-CoV-2 in children.

Infection from severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), though mainly a respiratory disease, can impair many systems, including causing hematological complications. Lymphopenia and hypercoagulability have been reported in adults with coronavirus disease 2019 (COVID-19) and are considered markers of poor prognosis. This review summarizes the hematological findings in children with SARS-CoV-2 infection. The majority of infected children had a normal leukocyte count, while the most common white blood cell abnormality was leukopenia. Lymphopenia, which may be a marker of severe disease, was rarer in children than in adults, possibly due to their immature immune system or due to the less severe manifestation of COVID-19 in this age group. Age may have an impact, and in neonates and infants the most common abnormality was lymphocytosis. Abnormalities of red blood cells and platelets were uncommon. Anemia and hypercoagulability were reported mainly in children presenting the novel multisystem inflammatory syndrome (MIS) associated with SARS-CoV-2.

Immune thrombocytopenic purpura in a patient with disseminated tuberculosis: An unusual presentation.

Pulmonary tuberculosis can have a wide variety of presentations including hematological manifestations. We report a case of a young male patient who presented with complaints of generalized petechiae, gum bleeding, systemic lymphadenopathy, and severe thrombocytopenia. His bone marrow revealed normal megakaryocytes, and in the absence of hepatosplenomegaly, a diagnosis of immune thrombocytopenic purpura (ITP) was made. The thrombocytopenia responded to course of intravenous immune globulin. The smear made from fine-needle aspiration of cervical lymph nodes showed acid-fast bacilli. This case highlights the rare association of extrapulmonary tuberculosis with ITP.

[Diagnosis of inherited thrombocytopenia]. / Les thrombopénies constitutionnelles : démarche diagnostique.

Inherited thrombocytopenias are rare, heterogenous and probably under-diagnosed because often classified as autoimmune thrombocytopenia. About 20 genes were described responsible for these thrombocytopenias. Precise diagnosis is necessary because the prognosis is different and some of them can evolve into hemopathies. First of all, it is important to gather a body of evidence to orientate towards an inherited cause: presence of the thrombocytopenia since childhood and of other family cases is a strong argument. Secondly, it is difficult to target the genetic investigations that settle the precise diagnosis. Genetic variants responsible for inherited thrombocytopenias affect different stage during megakaryocytopoiesis and cause thrombocytopenias with distinct characteristics. Presence of extra-hematological features, platelets' size measurement and evaluation of bone marrow megakaryocyte morphology when it is possible allow a primary orientation. We propose a diagnostic approach considering extra-hematological features, mode of inheritance, morphology, molecular and functional platelets' studies and bone marrow megakaryocyte morphology in order to better target genetic study. Nevertheless, despite this approach, some inherited thrombocytopenias remain still unexplained and could benefit from new methods of new generation sequencing in the future.

A study of the prevalence of serum vitamin B12 and folic Acid deficiency in Western maharashtra.

CONTEXT: This study summarizes the prevalence of vitamin B12 and folic acid deficiency in the population coming to tertiary care center in Western Maharashtra along with the main presenting symptom routinely misinterpreted in daily practice. AIMS AND OBJECTIVES: 1. To study the prevalence of vitamin B12 and folic acid deficiency in the population of western Maharashtra. 2. To correlate the symptoms with serum vitamin B12 and folic acid levels. MATERIALS AND METHODS: The present study is a cross-sectional observation study carried out on patients from western Maharashtra seeking medical attention on outpatient and inpatient basis in the medicine department of a teaching institute in Karad. One-hundred patients were selected on basis of below mentioned symptoms viz. tingling and numbness in extremities, dizziness, unsteady gait, early tiredness, forgetfulness, proximal weakness, distal weakness, chronic headache, less interest in work, chronic loose stools, strict vegetarians, alcoholics, intake of medications like anti-tubercular treatment, surgery involving terminal ileum. Serum vitamin B12 and folic acid levels of these patients were observed. Deficiency of vitamin B12 and folic acid was studied in 4 groups: (a) Absolute vitamin B12 deficiency; (b) Absolute folic acid deficiency; (c) Borderline vitamin B12 deficiency; (d) Combined vitamin B12 and folic acid deficiency. RESULTS: Of the 100 cases, 33% patients were vegetarian. Folic acid deficiency formed the major chunk of deficiency group. Six percent patients had neuropsychiatric manifestations. Depressive illness in 1% patients, dementia in 0% patients, forgetfulness in 1% patients, mania/hallucination in 0% patients each, and chronic headache in 1% patients. Neuropathy in form of loss of reflexes, decreased touch sensation was present in 9% patients. Posterior column involvement viz. Loss of joint position, vibration, positive Romberg's sign were present in 34% patients of vitamin B12 and folic acid deficiency. CONCLUSION: In a small study, it was found that megaloblastic anemia may have symptoms and signs referable to several systems including hematology, dermatology, gastrointestinal, neurology, and neuropsychiatry.

Pediatric lupus: varied haematological picture and presentation.

Systemic lupus erythematosus (SLE) is a chronic, multisystem, autoimmune disease characterized by periods of increased disease activity caused by inflammation of blood vessels and connective tissue. Pediatric patients with SLE have a more severe clinical course when compared with adults. Patients commonly present with rash, fever, and arthritis, although the presentation may be unpredictable. Hematological findings are more predominant in children than adults. Thirty-nine percent of children with SLE will develop hematological abnormalities, one of the American Rheumatic Association criteria for classifying the disease. In our case series we found varied hematological picture and presentation. We present here four case reports of SLE cases with interesting hematological features. Our first case is a 13 month old female child who was initially diagnosed as Evans syndrome and 2 years later diagnosed as SLE. Second case is a 3 year old male child who had SLE with warm antibody AIHA. Third case is a 6 year old female child who presented with AIHA and was diagnosed with SLE 6 years later. Fourth case is a 6 year old female child diagnosed as SLE with aplastic anemia. Hematological findings should be carefully assessed and treated in order to decrease disease related morbidity.