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Experimental Hematology Jun 2024SAMD9 and SAMD9L are two interferon-regulated genes located adjacent to each other on chromosome 7q21.2. Germline gain-of-function (GL GOF) mutations in SAMD9/SAMD9L are... (Review)
Review
SAMD9 and SAMD9L are two interferon-regulated genes located adjacent to each other on chromosome 7q21.2. Germline gain-of-function (GL GOF) mutations in SAMD9/SAMD9L are the genetic cause of MIRAGE syndrome, ataxia-pancytopenia (ATXPC) syndrome, myeloid leukemia syndrome with monosomy 7 (MLSM7), refractory cytopenia of childhood (RCC), transient monosomy 7 in children, SAMD9L-associated autoinflammatory disease (SAAD), and a proportion of inherited aplastic anemia and bone marrow failure syndromes. The myeloid neoplasms associated with GL GOF SAMD9/SAMD9L mutations have been included in the World Health Organization (WHO) 2022 classification. The discovery of SAMD9/SAMD9L-related diseases has revealed some interesting pathobiological mechanisms, such as a high rate of primary somatic compensation, with one of the mechanisms being (transient) monosomy 7 a mechanism also described as "adaption by aneuploidy." The somatic compensation in the blood can complicate the diagnosis of SAMD9/SAMD9L-related disease when relying on hematopoietic tissues for diagnosis. Recently, GL loss-of function (LOF) mutations have been identified in older individuals with myeloid malignancies in accordance with a mouse model of SAMD9L loss that develops a myelodysplastic syndrome (MDS)-like disease late in life. The discovery of SAMD9/SAMD9L-associated syndromes has resulted in a deeper understanding of the genetics and biology of diseases/syndromes that were previously oblivious and thought to be unrelated to each other. Besides giving an overview of the literature, this review wants to also provide some practical guidance for the classification of SAMD9/SAMD9L variants that is complicated by the nonrecurrent nature of these mutations but also by the fact that both GL GOF, as well as loss-of-function mutations, have been identified.
Topics: Humans; Chromosomes, Human, Pair 7; Myelodysplastic Syndromes; Chromosome Deletion; Animals; Intracellular Signaling Peptides and Proteins; Tumor Suppressor Proteins
PubMed: 38649131
DOI: 10.1016/j.exphem.2024.104217 -
The Journal of International Medical... Aug 2023The spleen is part of the lymphatic system and is one of the least understood organs of the human body. It is involved in the production of blood cells and helps filter...
OBJECTIVE
The spleen is part of the lymphatic system and is one of the least understood organs of the human body. It is involved in the production of blood cells and helps filter the blood, remove old blood cells, and fight infection. Partial splenic artery embolization (PSE) is widely used to treat pancytopenia and portal hypertension. The efficacy of PSE for improving thrombocytopenia has been well demonstrated. In this study, we evaluated the splenic infarction ratio and platelet increase ratio after PSE.
METHODS
Forty-five consecutive patients underwent PSE from January 2014 to August 2022. We retrospectively evaluated the splenic infarction volume and ratio after PSE and analyzed the relationship between the splenic infarction ratio and platelet increase ratio after PSE.
RESULTS
The platelet increase ratio was correlated with the splenic infarction ratio after PSE. The cutoff value for the splenic infarction ratio with a two-fold platelet increase was 63.0%.
CONCLUSION
We suggest performance of PSE in patients with a splenic infarction ratio of 63% to double the expected platelet count.
Topics: Humans; Splenic Infarction; Hypersplenism; Retrospective Studies; Splenic Artery
PubMed: 37560966
DOI: 10.1177/03000605231190967 -
Severe Bone Marrow Aplasia Following Macrophage Activation Syndrome in Systemic Lupus Erythematosus.The Tohoku Journal of Experimental... Aug 2023Macrophage activation syndrome (MAS) is a potentially fatal complication of rheumatic diseases, characterized by activated macrophages with hemophagocytosis and multiple...
Macrophage activation syndrome (MAS) is a potentially fatal complication of rheumatic diseases, characterized by activated macrophages with hemophagocytosis and multiple organ damage. We report a case of MAS associated with systemic lupus erythematosus that initially presented with severe liver dysfunction. Although it was improved with steroids and plasmapheresis, severe pancytopenia was subsequently experienced, and the bone marrow showed severe aplasia similar to aplastic anemia. Nevertheless, the administration of immunosuppressants resulted in the recovery of blood counts within two weeks. When severe MAS results in cytokine overproduction, bone marrow aplasia may occur, for which immunosuppressive therapy may be highly effective.
PubMed: 37164698
DOI: 10.1620/tjem.2023.J037 -
Journal of Community Hospital Internal... 2023Patients with granulomatous disease often have widespread pulmonary and extrapulmonary disease. In the absence of this, a search of the pulmonary, renal, hepatic,...
Patients with granulomatous disease often have widespread pulmonary and extrapulmonary disease. In the absence of this, a search of the pulmonary, renal, hepatic, ocular, and bone marrow is warranted in the setting of hypercalcemia with unexplained elevated 1,25-dihydroxyvitamin D, erythrocyte sedimentation rate (ESR), and C-reactive protein (CRP). We present a case of hypercalcemia and a decline in renal function in a patient with bone marrow sarcoidosis. A 45-year-old woman was admitted to the hospital after hypercalcemia, acute kidney injury, and pancytopenia were found on a routine outpatient lab. She was discharged after improvement with IV fluids. She had interval worsening of hypercalcemia and was readmitted within a week for pamidronate treatment. Imaging and labs were concerning for sarcoidosis, but bronchoscopy with biopsy was nondiagnostic. Eventual bone marrow biopsy confirmed evidence of granulomas. Her condition improved with prednisone over 3 months and ultimately, azathioprine. Non-parathyroid hormone-mediated hypercalcemia should be thoroughly worked up for a source to rule out malignancy and to diagnose treatable causes such as sarcoidosis. Sarcoidosis may not present in its traditional pulmonary pattern, necessitating further diagnostic measures such as a bone marrow biopsy.
PubMed: 38596540
DOI: 10.55729/2000-9666.1257 -
Journal of Infection and Public Health Dec 2023Recently, a wide range variety of manifestations, including a self‑limiting to severe illness, has been increasingly reported in dengue. Few studies attract attention...
BACKGROUND
Recently, a wide range variety of manifestations, including a self‑limiting to severe illness, has been increasingly reported in dengue. Few studies attract attention to severe dengue, mainly observed in secondary infection. With this background, this study aims to provide a comprehensive overview to differentiate primary from secondary dengue using serology (IgG) and the possible association of severity of illness in secondary dengue.
METHODS
Present retrospective cross-sectional study was conducted at a North Indian tertiary care center from September 2021 to January 2022. Clinical data of confirmed dengue patients from the medicine department were collected and assigned as primary and secondary dengue.
RESULTS
Of the 220 dengue patients, 22 (10 %) had secondary dengue infection. Hemorrhagic manifestations were reported in 58/220 (26.4 %) cases while 7/22 (31.8 %) in secondary dengue. Prevalent hemorrhagic manifestations in secondary dengue include purpura (27.3 %), vaginal bleeding (4.5 %), melaena (9.1 %), and epistaxis (4.5 %). In addition, 42 (19.1 %) patients had pancytopenia, and 8 (36.6 %) cases were of secondary dengue. Hepatic dysfunction was noted in 164 (74.5 %) cases. Notably, all secondary dengue cases (22;100 %) had hepatic dysfunction and severe in 9 (40.9 %) cases. In addition, in secondary dengue patients, evidence of plasma leakages such as hypoproteinemia 7 (31.8 %) and ascites (35 %) were statistically more frequent. Overall, two deaths (0.9 %) were reported, and were one in each group.
CONCLUSIONS
Many parameters, including hemorrhagic manifestation (melaena), hematological characteristic (pancytopenia), evidence of plasma leakage (hypoproteinemia and ascites), gastrointestinal (GB wall thickening and hepatic dysfunction) and reduction in mean hemoglobin and platelet count were found to be statistically significant in secondary dengue infection. Additionally, early classification of secondary dengue may help to anticipate its severity and allow for early strategic intervention/management to lower morbidity and mortality.
Topics: Female; Humans; Dengue; Cross-Sectional Studies; Coinfection; Tertiary Care Centers; Melena; Pancytopenia; Retrospective Studies; Ascites; India; Hypoproteinemia
PubMed: 37866270
DOI: 10.1016/j.jiph.2023.10.006 -
Transplant Immunology Oct 2023Mutations in the DNA ligase IV (LIG4) gene cause a rare autosomal recessive disorder called LIG4 deficiency syndrome. The LIG4 deficiency is featured by severe...
BACKGROUND
Mutations in the DNA ligase IV (LIG4) gene cause a rare autosomal recessive disorder called LIG4 deficiency syndrome. The LIG4 deficiency is featured by severe disorders, including combined immunodeficiency disease, special face ("bird-head-like" face), developmental delays, pancytopenia, and radiosensitivity. Currently there are no curative treatment options except potentially by performing a hematopoietic stem cell transplantation (HSCT).
CASE PRESENTATION
Here we reported the clinical course of a 4 and 1/2-year-old Chinese female with LIG4-deficiency featured with pancytopenia, severe growth retardation (weight of 13.5 kg, < 3rd percentile), length of 100 cm (<2d percentile), head circumference of 46 cm (<3rd percentile), and mild microcephaly. Despite regular IVIG administrations (5 g, once a month), the patient's thrombocytopenia had progressed. Eventually, the patient received HSCT that successfully normalized the LIG4 syndrome associated pancytopenia and corrected the LIG4 mutation. Despite progress the patient succumbed to thrombotic microangiopathy more than 3 months after HSCT.
CONCLUSIONS
This case reports an example of partially successful HSCT as a treatment option for LIG4 syndrome. It is possible that individual factors influence the therapeutic effect of HSCT in LIG4 deficiency.
Topics: Female; Humans; Pancytopenia; Immunologic Deficiency Syndromes; Growth Disorders; Hematopoietic Stem Cell Transplantation
PubMed: 37437665
DOI: 10.1016/j.trim.2023.101897 -
Clinical Medicine & Research Sep 2023Here we report development of hemophagocytic lymphohistiocytosis (HLH), along with unmasking of a TET2-mutated myeloid neoplasm, after initial doses of bendamustine and...
Here we report development of hemophagocytic lymphohistiocytosis (HLH), along with unmasking of a TET2-mutated myeloid neoplasm, after initial doses of bendamustine and rituximab for longstanding chronic lymphocytic leukemia (CLL). After many years of CLL showing minimally progressive lymphocytosis, the patient's white blood cell count began to decline in parallel with neutrophil count, hemoglobin, and platelet count. Bone marrow biopsy showed partial CLL involvement; bendamustine+rituximab therapy was augmented with granulocyte colony-stimulating factor (g-CSF) and romiplostim to mitigate worsening pancytopenia, without response. Laboratory evaluation revealed a pattern supportive of the clinical impression of HLH, while bone marrow biopsy showed persistent CLL, new reticulin fibrosis, megakaryocytic proliferation, and 32% mutated TET2, but no compelling morphologic evidence of hemophagocytosis. The patient recovered with dexamethasone and g-CSF support.
Topics: Humans; Leukemia, Lymphocytic, Chronic, B-Cell; Lymphohistiocytosis, Hemophagocytic; Rituximab; Bendamustine Hydrochloride; Granulocyte Colony-Stimulating Factor; DNA-Binding Proteins; Dioxygenases
PubMed: 37985171
DOI: 10.3121/cmr.2023.1804 -
Journal of Surgical Case Reports Feb 2024Lymphadenopathy in an immunosuppressed patient raises the quintessential diagnostic dilemma: infection or malignancy? We present the case of a transplant recipient on...
Lymphadenopathy in an immunosuppressed patient raises the quintessential diagnostic dilemma: infection or malignancy? We present the case of a transplant recipient on anti-rejection prophylaxis admitted with acute fever, malaise and a swollen right axillary node. The patient had pancytopenia and tested positive for Epstein-Barr virus; nodal core biopsy demonstrated atypical plasma cell infiltration, immediately raising suspicion for post-transplant lymphoproliferative disorder. However, excisional biopsy and serology clarified a final diagnosis of cat-scratch disease-a potentially fatal zoonosis requiring a disparate treatment regimen. Here, we explore this patient's investigations, hospital course and recovery, with an emphasis on recognizing and differentiating these diagnostic mimics in post-transplant practice.
PubMed: 38333562
DOI: 10.1093/jscr/rjad223 -
European Journal of Case Reports in... 2024Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease, characterised by multi-organ affections. Haematological involvement is a common manifestation of...
BACKGROUND
Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease, characterised by multi-organ affections. Haematological involvement is a common manifestation of SLE, consisting of autoimmune peripheral cytopenia. Autoimmune myelofibrosis (AIMF) is a rare cause of cytopenia in SLE; it could precede or be concurrent with the diagnosis of SLE. There are few studies that describe this association.
CASE DESCRIPTION
We report a case of AIMF revealing the diagnosis of SLE in 34-year-old female, presented with episodes of gingival bleeding associated with peripheral inflammatory polyarthralgia, photosensitivity and deterioration of general condition. Clinical examination revealed a soft pitting oedema in the lower limbs. Laboratory investigations showed a pancytopenia, inflammatory biological syndrome, with positive 24-hour proteinuria and anti-native DNA antibodies. A bone marrow biopsy showed diffuse myelofibrosis associated with maturation disorders and no tumour infiltrate. Renal biopsy revealed proliferative glomerulonephritis class III with immune deposits.
CONCLUSION
The association of AIMF with SLE has been rarely reported, and it could be another cause for cytopenia in SLE.
LEARNING POINTS
Autoimmune myelofibrosis can be associated with systemic lupus erythematosus (SLE), even though it is rare.This association should be considered when pancytopenia is not well controlled during SLE, prompting a bone marrow biopsy to confirm the diagnosis.The therapeutic management of this association is the same as that used in SLE.
PubMed: 38846662
DOI: 10.12890/2024_004511 -
Cureus Apr 2024Tuberculosis (TB), caused by the bacteria , is a highly infectious and prevalent disease. It is the leading cause of death among communicable diseases and the fifth...
Tuberculosis (TB), caused by the bacteria , is a highly infectious and prevalent disease. It is the leading cause of death among communicable diseases and the fifth leading cause of all diseases in India. The diagnosis can be challenging due to the disease's unique appearance and various presentations. Disseminated TB is characterized by the involvement of two or more non-contiguous sites resulting from hematogenous extension of the disease. Clinical confirmation of the diagnosis of disseminated TB is based on bacteriological or histological evidence. Based on various studies, there is evidence that satisfactory results are obtained from treatment with first-line anti-tubercular drugs. When there is a delay in diagnosis and treatment, it can become a life-threatening condition. We present a case of a 38-year-old alcoholic male who presented with generalized edema, pain, and distension of the abdomen. According to the initial presentation, the provisional diagnosis made was alcoholic liver disease, but it was later diagnosed as disseminated TB with sputum-positive pulmonary TB with abdominal involvement in the form of ascites and hepatosplenomegaly along with hematological involvement as pancytopenia. The patient started showing drastic improvement after the initiation of anti-tubercular therapy.
PubMed: 38800156
DOI: 10.7759/cureus.58902