ABSTRACT
Case Report: A 25-year-old woman with history of Diamond-Blackfan anemia (DBA) presented with a 3- week history of weakness and fatigue. The patient was in her usual state of health until 3 weeks prior when she was diagnosed with COVID-19, at which time she experienced cough, congestion, weakness, and fatigue. She reported that the cough and congestion improved after a few days, but the fatigue and weakness progressively worsened. Admission labs were notable for a hemoglobin of 5.5 g/dL with a MCV of 119.3 fL. She received 2 units of packed RBCs with improvement in hemoglobin to 8.9 g/dL. The patient was diagnosed with DBA at birth via bone marrow biopsy and had been stable on chronic prednisone with a baseline hemoglobin around 8 g/dL. Prior to this admission, she has only required one transfusion at 3 months old. Her outpatient management involved close monitoring of her hemoglobin and increasing/decreasing prednisone based on her trending hemoglobin. She had been stable on 15 mg/day of prednisone for the past few years. Her hematologist was consulted, and the decision was made to increase her dose of prednisone to 20 mg/day resulting in resolution of symptoms and stabilization of her hemoglobin level. Discussion(s): We present a rare case of DBA with worsening anemia in the setting of a recent COVID-19 infection. The literature regarding the risk and complications of COVID-19 in these patients is severely limited, with no current data on disease management, outcomes, or predictors of morbidity. DBA is a rare, congenital erythroid red cell aplasia that typically presents in infancy with an estimated incidence of 5 cases per 1 million births. DBA is characterized by progressive macrocytic anemia, congenital malformations, and increased risk of endocrine dysfunction and malignancies. Glucocorticoids are the first-line therapy for DBA, although the exact mechanism of how they stimulate erythropoiesis in DBA remains unknown. In terms of patient prognosis, approximately 40% are steroid-dependent, 40% are transfusiondependent, and 20% go into remission by age 25 years. Copyright © 2023 Southern Society for Clinical Investigation.
ABSTRACT
Background: Vacuoles, E1 enzyme, X-linked, autoinfammatory, somatic (VEXAS) syndrome is a recently identifed disorder caused by somatic mutations in the UBA1 gene of myeloid cells. Various manifestations of pulmonary involvement have been reported, but a detailed description of lung involvement and radiologic fndings is lacking. Objectives: To describe lung involvement in VEXAS syndrome. Methods: A retrospective cohort study was conducted of all patients iden-tifed at the Mayo Clinic with VEXAS syndrome since October 2020. Clinical records and chest high resolution computed tomography (HRCT) scans were reviewed. Results: Our cohort comprised 22 white men with a median age of 69 years (IQR 62-74, range 57-84). Hematologic disorders including multiple myeloma, myelodysplastic syndrome and pancytopenia were present in 10 patients (45%), rheumatologic diseases including granulomatosis with poly-angiitis, IgG4-related disease, polyarteritis nodosa, relapsing polychondritis, and rheumatoid arthritis were found in 10 patients (45%), and 4 patients had dermatologic presentations including Sweet syndrome, Schnitzer-like syndrome or drug rash with eosinophilia skin syndrome (DRESS). VEXAS syndrome-related features included fever (18, 82%), skin lesions (20, 91%), lung infiltrates (12, 55%), chondritis (10, 45%), venous thromboembolism (12, 55%), macrocytic anemia (21, 96%), and bone marrow vacuoles (21, 96%). Other manifestations observed were arthritis, scleritis, hoarseness and hearing loss. Median erythrocyte sedimentation rate (ESR) was 69 mm/1st hour (IQR 34.3-118.8) and median C-reactive protein (CRP) of 55.5 mg/dL (IQR 11.4-98.8). The somatic mutations affecting methionine-41 (p.Met41) in UBA1 gene were: 11 (50%) p.Met41Thr, 7 (32%) p.Met41Val, 2 (9%) p.Met41Leu, and 2 (9%) in the splice site. All patients received glu-cocorticoids (GC) (median duration of treatment was 2.6 years);21 (96%) received conventional immunosuppressive agents (methotrexate, aza-thioprine, mycophenolate, leflunomide, cyclosporin, hydroxychloroquine, tofacitinib, ruxolitinib) and 9 (41%) received biologic agents (rituximab, tocilizumab, infliximab, etanercept, adalimumab, golimumab, abatacept). Respiratory symptoms included dyspnea and cough present in 21 (95%) and 12 (55%), respectively, and were documented prior to VEXAS diagnosis. Most of the patients were non-smokers (14, 64%) and obstructive sleep apnea (OSA) was present in 11 patients (50%). Seven patients (32%) used non-invasive ventilation, 6 used C-PAP, and 1 used Bi-PAP. Bronchoalveolar lavage (BAL) was available in 4 patients, and the findings were compatible with neutrophilic alveolitis in 3. Two patients had lung biopsies (2 transbronchial and 1 surgical) that showed ATTR amyloidosis and organizing pneumonia with lymphoid interstitial pneumonia, respectively. Pulmonary function tests were available in 9 (41%) patients and showed normal results in 5;3 patients had isolated reduction in DLCO and 1 with mild restriction. On chest HRCT, 16 patients (73%) had parenchymal changes including ground-glass opacities in 9, septal thickening in 4, and nodules in 3;pleural effusions were present in 3 patients, air-trapping in 3 patients and tracheomalacia in 1 patient. Follow-up chest HRCT was available for 8 patients (36%), the ground-glass opacities resolved in 5 patients, 3 patients manifested new or increased ground-glass opacities, and 1 patient had increased interlobular septal thickening. After 1 year of follow-up, 4 patients (17%) had died;3 due to pneumonia (2 COVID-19,1 bacterial) and 1 due to heart failure. VEXAS flares occurred in 18 patients (82%), the maximum number of relapses was 7, and they were mainly managed with GC and with changes in the immuno-suppressive regimen. Conclusion: Pulmonary involvement was documented by chest HRCT in most patients with VEXAS syndrome. Respiratory symptoms occurred in over one half of patients and about 20% had PFT abnormalities. The pulmonary manifestations of VEXAS are nonspecifc and characterized predominantly by infamma-tory parenchymal involvement.
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Background: The Severe Acute Respiratory Coronavirus 2 (SARS-CoV- 2) infection manifests itself through a wide range of clinical pictures, from the condition of asymptomatic carrier to severe respiratory insufficiencies and/or severe organ impairments, including a massive release of cytokines, an increase in the coagulation state, haemoglobin damage, dysregulation of iron homeostasis and iron overload. It has also been appreciated a normo/macrocytic anaemia in many patients, typically associated with phlogosis. In effect, the condition of inflammation deeply affects erythropoiesis through different mechanisms, both linked to an altered iron metabolism mediated by an increased production of interleukins, and caused by proinflammatory cytokines such as the interferon-γ, IL-1, IL-33 and the Tumour necrosis factor-α (TNF-α). Inflammatory cytokines, especially IL-6 and IL-1b, increase the production of hepcidin, which, by degrading ferroportin, the cellular exporter of iron, provokes a reduction in serum iron and a sequestration of iron at the macrophage level. This process deprives potential microorganisms of iron, but it can cause a typically macrocytic anaemia, also known as 'anaemia of chronic disorders'. An altered iron metabolism would therefore be expected also in the SARS-CoV-2 infection. Nevertheless, studies on alterations of the iron metabolism in this infection are still quite limited. Aims: Our study is a retrospective analysis aimed at understanding the Covid-related pathogenesis of anaemia through the data examination of patients transfused during the SARS-COV2 infection. Methods: In our Immunohematology and Transfusion Medicine Service, we have analysed the types of anaemia occurred in patients suffering from SARS-CoV-2 who have been subjected to blood transfusion in a period comprised between November 2020 and December 2021. We have evaluated data in relation to 29 patients presenting normo-macrocytic anaemia at the onset, subjected to a transfusion of prefiltered red blood cells. The analysed sample included 15 males and 14 females with an average age of 67 years (range: 40-96). Only 4 patients out of 29 had a haemorrhage at the onset. The other 25 patients did not incur into haemorrhagic episodes. Results: Average pre-transfusion blood counts have highlighted an average haemoglobin value of 7.5 g/dl (range: 6.4-9.2) with an average globular volume of 93 fL (range: 65.3-105). Patients have been transfused on average with 4 units of prefiltered red blood cells (range: 1-24). All patients presented a severe phlogosis documented by average ferritin values of 520 ng/ml (range: 355-1200) and of CRP of 8.7 mg/dl (range: 1.79-25). Summary/Conclusions: Analysed data lead us to think that, as it has been confirmed by the scarce literature on the matter, the majority of cases of anaemia associated with a SARS-CoV-2 infection has an inflammatory pathogenesis. The high values of the serum ferritin and of the CRP strengthen this hypothesis. There is surely an additional etiopathogenetic component of bone marrow inhibition on the erythrocyte maturation associated with an alteration of iron metabolism, as it can be deduced from the increase in the average globular value.
ABSTRACT
A 46-years old Egyptian man was admitted to our department because of the onset of worsening dyspnea. In his clinical history were present: hypothyroidism, obesity, hyperuricemia, hypertension and recent Sars-Cov2 infection. Bilateral pleuric effusion was suspected during physical examination and confirmed by chest CT. Blood data showed mild macrocytic anemia, increased levels of creatinine, transaminases, pro-BNP (3574 pg/ml cut-off 0-125) and D-dimer. Multiple molecular swabs for research of Sars-Cov2 were negative. ECG showed sinus rhythm and non specific atypia of repolarization. An eco-fast was performed at bedside and revelead left ventricular dilatation and severe systolic disfunction due to diffuse hypokinesia (EF 30%). Diuretic therapy was set up with improvement of the clinical status. In order to exclude ischaemic genesis of the cardiopathy a coronary angiography was performed without evidence of obstructive lesions. An echocardiogram was repeated and it showed a parietal ipertrabeculation of the left ventricle. This aspect was suggestive of non-compact myocardium, a rare disease due to the arrest of the myocardial maturation process during fetal development, leading to the persistence of embryonic structures in the heart muscle. Genetic inheritance arises in 30-50% of patients and are involved genes that generally seem to encode sarcomeric or cytoskeletal proteins.Cardiac MRI is planned in order to have further confirmation of our diagnostic hypothesis. In the meantime wearable defibrillator was prescribed for the prevention of sudden death.
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Objective: To classify the haematological pattern, severity of anemia in children 5-12 years age admitted and to find its correlation with the clinical conditions. Methods Crossectional study of 160 patients in two years was done. Patients satisfying the inclusion criteria were selected for study. Relevant clinical data were recorded in a structured proforma including detailed history was recorded with particular symptoms suggestive of anemia such as weakness and easily fatigability, breathlessness on exertion and pica. A thorough clinical examination of every child was done followed by routine investigations for anemia Results Patients between 7-8 year were found to be the most affected. Anemia was found to be more common in female children as compared to male children (F:M=1.13). Anemia is more common in undernourished child. Most common presenting symptoms were gastrointestinal including vomiting, diarrhea and pain abdomen. Most common sign was Pallor followed by other common signs included signs of dehydration associated with diarrhea, hepatosplenomegaly. microcytic hypochromic anemia was the most common morphological type of anemia and macrocytic anemia was the least common.Thalassemia cases were most common among hemolytic anemias. Iron Deficiency Anemia (Nutritional Anemia) was the most common etiology of anemia. Conclusion Dietary deficits affect children aged 5 to 12, creating financial, emotional, and psychological burden for patients and their families, as well as depleting critical national resources. As a result, screening for these illnesses, as well as early detection of anemia and related problems, is essential.
ABSTRACT
Cytogenetic abnormalities involving chromosome 16 are found in 5– 8% of acute myeloid leukemia (AML). These are typically a pericentric inversion inv(16)(p13.1q22) or a translocation, t(16;16)(p13.1;q22), involving the MYH11 and CBFB genes localized to chromosome 16p13.1 and 16q22, respectively. In addition, less common rearrangements include deletion of the long arm of chromosome 16, del(16) (q22), and cryptic insertions involving the MYH11 and the CBFB genes with otherwise normal karyotypes. In this report, we present the first AML case with a new translocation involving the CBFB gene. The more common CBFB - MYH11 fusion product resulting from the inversion and/or translocation of chromosome(s) 16 leads to an AML with monocytic and granulocytic differentiation and abnormal eosinophil component with large, purple to violet color eosinophilic granules. This entity typically corresponds to the adult AML-M4Eo in French-American- British (FAB) Classification and now called AML with inv(16)(p13.1q22) or t(16;16)(p13.1;q22);CBFB-MYH1 in the new 2017 WHO Classification. Patients may present with myeloid sarcoma at initial diagnosis or at relapse. We present a case of an 80-year-old male with a history of prostate cancer post radiotherapy who was referred for COVID-19 testing. A complete blood count with differential revealed neutropenia and a macrocytic anemia. A bone marrow biopsy and a bone marrow aspirate confirmed a diagnosis of AML with 33% blasts including myeloblasts and promonocytes. Interphase fluorescence in situ hybridization (FISH) analysis with a break-apart probe for CBFB showed an abnormal hybridization pattern consistent with rearrangement of CBFB in 66% of nuclei. Chromosome analysis revealed an abnormal karyotype with two related clones: 47,XY, t(10;16)(p13;q22),+22[4]/48,idem,+8[16]. Sequential GTG-FISH confirmed that the 3’ region of CBFB was translocated to 10p13 in the t(10;16) and the 5’ region remained on 16q. Based on the karyotype, the patient’s bone barrow exhibits clonal evolution having acquired additional chromosome abnormalities (trisomy 22 and trisomy 8). Molecular studies by next generation sequencing showed NRAS p.Gln61Lys mutation with a VAF of 11.21%. No genomic alterations were detected in KIT, KRAS or FLT3 genes. AML with inv(16)(p13.1q22) or t(16;16)(p13.1;q22) is associated with a high rate of complete remission and favorable overall survival when treated with intensive consolidation therapy. However, their prognostic advantage may be affected by additional cytogenetic abnormalities and/or other gene mutations. Specifically, trisomy 22, is a frequent abnormality additional to inv(16) detected as a secondary finding which has been associated with an improved outcome when compared to the prognosis associated with inv(16) alone. Furthermore, KIT (in 30–40%), FLT3 (in 14%), NRAS (in 45%) and KRAS (in 13%) mutations are common in this AML type. The prognostic implications of KIT mutation (especially involving exon 8) do not appear to be significantly poor prognostic compared to other AML types. On the other hand FLT3-TKD mutations and trisomy 8 are associated with a worse outcome. The patient is currently receiving Vidaza 75 mg/m2, days 1–7 of a 28 days cycle with Venetoclax mg daily of a 28-day cycle and his clinical prognosis is currently unclear. Further analysis by DNA sequencing may help to characterize the molecular nature of the fusion gene product resulting from the novel t(10;16)(p13;q22). To the best of our knowledge, this is the first reported case of an AML patient with translocation t(10;16)(p13;q22) involving the CBFB gene. Given the rarity and lack of additional information regarding the effects of this abnormality, the prognosis and survival cannot be predicted.