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Cureus Oct 2023Red blood cells (RBCs) start to break down early in hemolytic anemia, which can be chronic or life-threatening. It should be considered while determining if normocytic... (Review)
Review
Red blood cells (RBCs) start to break down early in hemolytic anemia, which can be chronic or life-threatening. It should be considered while determining if normocytic or macrocytic anemia is present. Hemolysis in the reticuloendothelial system may happen intravascularly, extravascularly, or both. It accounts for a broad spectrum of laboratory and clinical situations, both physiological and pathological. Whenever the frequency of RBC breakdown is rapid enough to lower hemoglobin levels below the normal range, hemolytic anemia occurs. Microangiopathic hemolytic anemia (MAHA) is a term used to describe non-immune hemolysis induced by intravascular RBC fragmentation caused by substances in the tiny blood arteries that generate schistocytes in the peripheral circulation. Microvasculature abnormalities, such as small arterioles and capillaries, are usually involved. Furthermore, MAHA can also be brought on by intravascular devices like a prosthetic heart valve or assistive technologies. Poor deformity results in entrapment, phagocytosis, antibody-mediated elimination through phagocytosis or direct complement activation, fragmentation brought about by microthrombi or acute mechanical stress, oxidation, or spontaneous cellular death. Hemolysis may cause acute anemia, jaundice, hematuria, dyspnea, tiredness, tachycardia, and possibly hypotension. This article aims to synthesize existing research, identify therapeutic strategies, and provide insights into current and emerging approaches for managing this complex hematological disorder.
PubMed: 38021690
DOI: 10.7759/cureus.47196 -
Medicina (Kaunas, Lithuania) Nov 2023Diamond-Blackfan anemia (DBA) is a congenital bone marrow failure syndrome associated with malformations. DBA is related to defective ribosome biogenesis, which impairs... (Review)
Review
Diamond-Blackfan anemia (DBA) is a congenital bone marrow failure syndrome associated with malformations. DBA is related to defective ribosome biogenesis, which impairs erythropoiesis, causing hyporegenerative macrocytic anemia. The disease has an autosomal dominant inheritance and is commonly diagnosed in the first year of life, requiring continuous treatment. We present the case of a young woman who, at the age of 21, developed severe symptomatic anemia. Although, due to malformations, a congenital syndrome had been suspected since birth, a confirmation diagnosis was not made until the patient was referred to our center for an evaluation of her anemia. In her neonatal medical history, she presented with anemia that required red blood cell transfusions, but afterwards remained with a stable, mild, asymptomatic anemia throughout her childhood and adolescence. Her family history was otherwise unremarkable. To explain the symptomatic anemia, vitamin deficiencies, autoimmune diseases, bleeding causes, and myeloid and lymphoid neoplasms were investigated and ruled out. A molecular investigation showed the RPL5 gene variant c.392dup, p.(Asn131Lysfs*6), confirming the diagnosis of DBA. All family members have normal blood values and none harbored the mutation. Here, we will discuss the unusual evolution of this case and revisit the literature.
Topics: Humans; Young Adult; Infant, Newborn; Female; Adolescent; Child; Frameshift Mutation; Ribosomal Proteins; Mutation; Anemia, Diamond-Blackfan; Phenotype
PubMed: 38004002
DOI: 10.3390/medicina59111953 -
Role of Cytokine-Inducible SH2 Domain-Containing (CISH) Protein in the Regulation of Erythropoiesis.Biomolecules Oct 2023The cytokine-inducible SH2 domain-containing (CISH) protein was the first member of the suppressor of cytokine signaling (SOCS) family of negative feedback regulators...
The cytokine-inducible SH2 domain-containing (CISH) protein was the first member of the suppressor of cytokine signaling (SOCS) family of negative feedback regulators discovered, being identified in vitro as an inducible inhibitor of erythropoietin (EPO) signaling. However, understanding of the physiological role played by CISH in erythropoiesis has remained limited. To directly assess the function of CISH in this context, mice deficient in CISH were characterized with respect to developmental, steady-state, and EPO-induced erythropoiesis. was strongly expressed in the fetal liver, but CISH knockout (KO) mice showed only minor disruption of primitive erythropoiesis. However, adults exhibited mild macrocytic anemia coincident with subtle perturbation particularly of bone marrow erythropoiesis, with EPO-induced erythropoiesis blunted in the bone marrow of KO mice but enhanced in the spleen. was expressed basally in the bone marrow with induction following EPO stimulation in bone marrow and spleen. Overall, this study indicates that CISH participates in the control of both basal and EPO-induced erythropoiesis in vivo.
Topics: Animals; Mice; Anemia; Cytokines; Erythropoiesis; Signal Transduction; src Homology Domains; Suppressor of Cytokine Signaling Proteins
PubMed: 37892192
DOI: 10.3390/biom13101510 -
Medical & Biological Engineering &... Feb 2024The photoacoustic effect is an attractive tool for diagnosis in several biomedical applications. Analyzing photoacoustic signals, however, is challenging to provide...
The photoacoustic effect is an attractive tool for diagnosis in several biomedical applications. Analyzing photoacoustic signals, however, is challenging to provide qualitative results in an automated way. In this work, we introduce a dynamic modeling scheme of photoacoustic sensor data to classify blood samples according to their physiological status. Thirty-five whole human blood samples were studied with a state-space model estimated by a subspace method. Furthermore, the samples are classified using the model parameters and the linear discriminant analysis algorithm. The classification performance is compared with time- and frequency-domain features and an autoregressive-moving-average model. As a result, the proposed analysis can predict five blood classes: healthy women and men, microcytic and macrocytic anemia, and leukemia. Our findings indicate that the proposed method outperforms conventional signal processing techniques to analyze photoacoustic data for medical diagnosis. Hence, the method is a promising tool in point-of-care devices to detect hematological diseases in clinical scenarios.
Topics: Male; Humans; Female; Signal Processing, Computer-Assisted; Spectrum Analysis; Photoacoustic Techniques
PubMed: 37880558
DOI: 10.1007/s11517-023-02939-3 -
Cureus Aug 2023Isolated thrombocytopenia in adults is a common clinical problem, often caused by various hematological disorders. However, vitamin B12 deficiency as a rare cause of...
Isolated thrombocytopenia in adults is a common clinical problem, often caused by various hematological disorders. However, vitamin B12 deficiency as a rare cause of isolated thrombocytopenia has been rarely reported in the medical literature. This case report aims to highlight the diagnostic challenges associated with atypical presentations of thrombocytopenia and emphasizes the importance of considering nutritional deficiencies, such as vitamin B12 deficiency, in the diagnostic workup. We report the case of a 38-year-old male who presented with generalized weakness, fatigue, and a history of bruises without trauma. Physical examination and laboratory investigations revealed thrombocytopenia (42 K/µL) with normal red blood cell morphology and no apparent abnormalities in other hematological parameters. Serum vitamin B12 levels were significantly diminished (128 pg/ml). The patient was treated with subcutaneous mecobalamin 1000 mcg supplementation, resulting in improvements in serum vitamin B12 levels (772 pg/ml) and platelet count (154 × 10/L) values. This case highlights the importance of considering vitamin B12 deficiency as a potential cause of isolated thrombocytopenia in adults. The lack of hypersegmented neutrophils and characteristic signs of macrocytic anemia in the context of vitamin B12 deficiency emphasizes the necessity for a thorough investigation to rule out other possible causes. Hematological problems associated with thrombocytopenia caused by vitamin B12 deficiency can be treated early to resolve them and avoid complications.
PubMed: 37753039
DOI: 10.7759/cureus.44162 -
Cureus Aug 2023Vitamin B12 (cobalamin) deficiency is a commonly seen nutritional deficiency that presents with a broad spectrum of clinical symptoms. In this report, we describe a case...
Vitamin B12 (cobalamin) deficiency is a commonly seen nutritional deficiency that presents with a broad spectrum of clinical symptoms. In this report, we describe a case of a 49-year-old female patient who presented to the emergency department with sudden onset of a syncopal-like episode, generalized weakness, and severe pancytopenia, who was subsequently diagnosed with vitamin B12 deficiency upon admission. The patient underwent a thorough evaluation to exclude alternative etiologies for her presentation. Her clinical symptoms and blood count significantly improved after six days of treatment with vitamin B12 supplementation. While vitamin B12 deficiency is a commonly recognized issue, healthcare providers should be aware of its infrequent presentations. Our case serves as a reminder to clinicians to remain vigilant for acute onset manifestations and consider vitamin B12 deficiency as a differential diagnosis for the early management of pancytopenia.
PubMed: 37746468
DOI: 10.7759/cureus.44017 -
Orphanet Journal of Rare Diseases Sep 2023Imerslund-Gräsbeck syndrome (IGS) is a rare autosomal recessive disorder characterized by vitamin B12 malabsorption. Most patients present with non-specific symptoms... (Review)
Review
Imerslund-Gräsbeck syndrome (IGS) is a rare autosomal recessive disorder characterized by vitamin B12 malabsorption. Most patients present with non-specific symptoms attributed to vitamin B12 deficiency, and proteinuria. Patients may if untreated, develop severe neurocognitive manifestations. If recognized and treated with sufficient doses of vitamin B12, patients recover completely. We provide, for the first time, an overview of all previously reported cases of IGS. In addition, we provide a complete review of IGS and describe two new patients.
Topics: Humans; Vitamin B 12 Deficiency; Anemia, Megaloblastic; Proteinuria; Vitamin B 12
PubMed: 37710296
DOI: 10.1186/s13023-023-02889-x -
Annals of the Rheumatic Diseases Dec 2023The vacuoles, E1-enzyme, X linked, autoinflammatory and somatic (VEXAS) syndrome is an adult-onset autoinflammatory disease (AID) due to postzygotic variants.
BACKGROUND
The vacuoles, E1-enzyme, X linked, autoinflammatory and somatic (VEXAS) syndrome is an adult-onset autoinflammatory disease (AID) due to postzygotic variants.
OBJECTIVES
To investigate the presence of VEXAS syndrome among patients with adult-onset undiagnosed AID. Additional studies evaluated the mosaicism distribution and the circulating cytokines.
METHODS
Gene analyses were performed by both Sanger and amplicon-based deep sequencing. Patients' data were collected from their medical charts. Cytokines were quantified by Luminex.
RESULTS
Genetic analyses of enrolled patients (n=42) identified 30 patients carrying pathogenic variants, with frequencies compatible for postzygotic variants. All patients were male individuals who presented with a late-onset disease (mean 67.5 years; median 67.0 years) characterised by cutaneous lesions (90%), fever (66.7%), pulmonary manifestations (66.7%) and arthritis (53.3%). Macrocytic anaemia and increased erythrocyte sedimentation rate and ferritin were the most relevant analytical abnormalities. Glucocorticoids ameliorated the inflammatory manifestations, but most patients became glucocorticoid-dependent. Positive responses were obtained when targeting the haematopoietic component of the disease with either decitabine or allogeneic haematopoietic stem cell transplantation. Additional analyses detected the variants in both haematopoietic and non-haematopoietic tissues. Finally, analysis of circulating cytokines did not identify inflammatory mediators of the disease.
CONCLUSION
Thirty patients with adult-onset AID were definitively diagnosed with VEXAS syndrome through genetic analyses. Despite minor interindividual differences, their main characteristics were in concordance with previous reports. We detected for the first time the mosaicism in non-haematopoietic tissue, which questions the previous concept of myeloid-restricted mosaicism and may have conceptual consequences for the disease mechanisms.
Topics: Adult; Humans; Male; Female; Mosaicism; Arthritis; Cytokines; Ferritins; Glucocorticoids; Mutation
PubMed: 37666646
DOI: 10.1136/ard-2023-224460 -
Cureus Aug 2023While macrocytic anemia is common in vitamin B12 deficiency, rarely, pancytopenia and hemolytic anemia can occur. Homocysteine levels are elevated in severe B12...
While macrocytic anemia is common in vitamin B12 deficiency, rarely, pancytopenia and hemolytic anemia can occur. Homocysteine levels are elevated in severe B12 deficiency, and this is linked to thrombus formation with potentially life-threatening complications. We present a patient with severe vitamin B12 deficiency complicated by hyperhomocysteinemia and obstructive shock from pulmonary embolism. A 56-year-old male with no medical history presented to the hospital with altered mentation. The patient's family stated he was experiencing bilateral paresthesias of his lower extremities, progressive depression, anxiety, and insomnia. Initial vitals were blood pressure of 76/36, heart rate of 70 beats per minute, respiratory rate of 14, and temperature of 36.3 degrees Celsius. He was intubated due to severe encephalopathy. Relevant labs indicated severe macrocytic anemia, thrombocytopenia, decreased B12 levels, elevated methylmalonic acid, and elevated homocysteine. Imaging demonstrated a right common femoral vein thrombosis and subsegmental pulmonary emboli. Peripheral blood smear revealed schistocytes, anisopoikilocytosis, and decreased platelet count. The patient required fluid resuscitation, antibiotics, and multiple blood products. Vitamin B12 was administered intramuscularly, which improved the anemia. Esophagogastroduodenoscopy (EGD) demonstrated gastritis. Gastric and duodenal biopsies were negative for and celiac disease. He was negative for intrinsic factor (IF) antibodies but had elevated gastrin levels. An intravenous unfractionated heparin infusion was started when the platelet count was above 50000. The patient was extubated after seven days. Heparin was transitioned to apixaban and an inferior vena cava (IVC) filter was placed. Hyperhomocysteinemia is a known pro-thrombotic factor that can lead to the development of venous thromboembolism. B12 malabsorption can stem from inflammatory bowel disease, celiac disease, gastritis, pancreatic insufficiency, gastrectomy, gastric bypass surgery, or antibodies to IF. While this case showed gastritis and negative IF antibodies, gastrin levels were elevated, indicating a mixed picture. This highlights the challenge of definitively diagnosing pernicious anemia as the cause of vitamin B12 deficiency. Vitamin B12 deficiency may lead to critical illness in which thromboembolism develops secondary to hyperhomocysteinemia.
PubMed: 37664295
DOI: 10.7759/cureus.42908 -
Gastroenterology Dec 2023
Topics: Humans; Stomach; Anemia; Upper Gastrointestinal Tract; Abdomen; Anemia, Pernicious; Stomach Neoplasms
PubMed: 37640254
DOI: 10.1053/j.gastro.2023.08.032