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International Journal of Molecular... Mar 2018Myelofibrosis (MF) is a clinical manifestation of chronic BCR-ABL1-negative chronic myeloproliferative neoplasms. Splenomegaly is one of the major clinical... (Review)
Review
Myelofibrosis (MF) is a clinical manifestation of chronic BCR-ABL1-negative chronic myeloproliferative neoplasms. Splenomegaly is one of the major clinical manifestations of MF and is directly linked to splenic extramedullary hematopoiesis (EMH). EMH is associated with abnormal trafficking patterns of clonal hematopoietic cells due to the dysregulated bone marrow (BM) microenvironment leading to progressive splenomegaly. Several recent data have emphasized the role of several cytokines for splenic EMH. Alteration of CXCL12/CXCR4 pathway could also lead to splenic EMH by migrated clonal hematopoietic cells from BM to the spleen. Moreover, low Gata1 expression was found to be significantly associated with the EMH. Several gene mutations were found to be associated with significant splenomegaly in MF. In recent data, homozygous mutation was associated with a larger spleen size. In other data, mutations in MF were signigicantly associated with longer larger splenomegaly-free survivals than others. In addition, MF patients with ≥1 mutations in AZXL1, EZH1 or IDH1/2 had significantly low spleen reduction response in ruxolitinib treatment. Developments of JAK inhibitors, such as ruxolitinib, pacritinib, momelotinib, and febratinib enabled the effective management in MF patients. Especially, significant spleen reduction responses of the drugs were demonstrated in several randomized clinical studies, although those could not eradicate allele burdens of MF.
Topics: Bone Marrow; Cell Movement; Chemokine CXCL12; Hematopoiesis, Extramedullary; Humans; Janus Kinase Inhibitors; Janus Kinases; Mutation; Primary Myelofibrosis; Randomized Controlled Trials as Topic; Receptors, CXCR4; Spleen; Splenomegaly
PubMed: 29562644
DOI: 10.3390/ijms19030898 -
Akkermansia muciniphila induces slow extramedullary hematopoiesis via cooperative IL-1R/TLR signals.EMBO Reports Dec 2023Bacterial infections can activate and mobilize hematopoietic stem and progenitor cells (HSPCs) from the bone marrow (BM) to the spleen, a process termed extramedullary...
Bacterial infections can activate and mobilize hematopoietic stem and progenitor cells (HSPCs) from the bone marrow (BM) to the spleen, a process termed extramedullary hematopoiesis (EMH). Recent studies suggest that commensal bacteria regulate not only the host immune system but also hematopoietic homeostasis. However, the impact of gut microbes on hematopoietic pathology remains unclear. Here, we find that systemic single injections of Akkermansia muciniphila (A. m.), a mucin-degrading bacterium, rapidly activate BM myelopoiesis and slow but long-lasting hepato-splenomegaly, characterized by the expansion and differentiation of functional HSPCs, which we term delayed EMH. Mechanistically, delayed EMH triggered by A. m. is mediated entirely by the MYD88/TRIF innate immune signaling pathway, which persistently stimulates splenic myeloid cells to secrete interleukin (IL)-1α, and in turn, activates IL-1 receptor (IL-1R)-expressing splenic HSPCs. Genetic deletion of Toll-like receptor-2 and -4 (TLR2/4) or IL-1α partially diminishes A. m.-induced delayed EMH, while inhibition of both pathways alleviates splenomegaly and EMH. Our results demonstrate that cooperative IL-1R- and TLR-mediated signals regulate commensal bacteria-driven EMH, which might be relevant for certain autoimmune disorders.
Topics: Humans; Hematopoiesis, Extramedullary; Splenomegaly; Bone Marrow; Hematopoietic Stem Cells; Hematopoiesis
PubMed: 37870318
DOI: 10.15252/embr.202357485 -
Annals of Hematology Apr 2023Myelofibrosis (MF) is a myeloproliferative neoplasm characterized by mutations (most frequently in JAK2, CALR, or MPL), burdensome symptoms, splenomegaly, cytopenia, and... (Review)
Review
Myelofibrosis (MF) is a myeloproliferative neoplasm characterized by mutations (most frequently in JAK2, CALR, or MPL), burdensome symptoms, splenomegaly, cytopenia, and shortened life expectancy. In addition to other clinical manifestations, patients with MF often develop anemia, which can either be directly related to MF pathogenesis or a result of MF treatment with Janus kinase (JAK) inhibitors, such as ruxolitinib and fedratinib. Although symptoms and clinical manifestations can be similar between the 2 anemia types, only MF-related anemia is prognostic of reduced survival. In this review, I detail treatment and patient management approaches for both types of anemia presentations and provide recommendations for the treatment of MF in the presence of anemia.
Topics: Humans; Primary Myelofibrosis; Janus Kinase 2; Splenomegaly; Nitriles; Anemia; Pyrrolidines; Sulfonamides
PubMed: 36786879
DOI: 10.1007/s00277-023-05126-4 -
Blood Nov 2019Common variable immune deficiency (CVID) is one of the most common congenital immune defects encountered in clinical practice. The condition occurs equally in males and... (Review)
Review
Common variable immune deficiency (CVID) is one of the most common congenital immune defects encountered in clinical practice. The condition occurs equally in males and females, and most commonly in the 20- to 40-year-old age group. The diagnosis is made by documenting reduced serum concentrations of immunoglobulin G (IgG), IgA, and usually IgM, together with loss of protective antibodies. The genetics of this syndrome are complex and are still being unraveled, but the hallmarks for most patients, as with other immune defects, include acute and chronic infections of the sinopulmonary tract. However, other noninfectious autoimmune or inflammatory conditions may also occur in CVID, and indeed these may be the first and only sign that a significant immune defect is present. These manifestations include episodes of immune thrombocytopenia, autoimmune hemolytic anemia, or neutropenia, in addition to splenomegaly, generalized or worrisome lymphadenopathy, and malignancy, especially lymphoma. These issues commonly bring the patient to the attention of hematologists for both evaluation and treatment. This article discusses 3 cases in which patients with CVID had some of these presenting issues and what hematology input was required.
Topics: Anemia, Hemolytic, Autoimmune; Common Variable Immunodeficiency; Humans; Lymphadenopathy; Lymphoma; Male; Middle Aged; Splenomegaly
PubMed: 31751486
DOI: 10.1182/blood.2019002062 -
Annals of Hematology Jul 2020Myelofibrosis (MF) is a chronic myeloproliferative neoplasm which can lead to massive splenomegaly secondary to extramedullary hematopoiesis. Patients frequently exhibit... (Review)
Review
Myelofibrosis (MF) is a chronic myeloproliferative neoplasm which can lead to massive splenomegaly secondary to extramedullary hematopoiesis. Patients frequently exhibit debilitating symptoms including pain and early satiety, in addition to cellular sequestration causing severe cytopenias. JAK 1/2 inhibitors, such as ruxolitinib and fedratinib, are the mainstay of therapy and produce significant and durable reductions in spleen volume. However, many patients are not eligible for JAK 2 inhibitor therapy or become refractory to treatment over time. Novel therapies are in development that can reduce the degree of splenomegaly for some of these patients. However, splenectomy, splenic irradiation, and partial splenic artery embolization remain valuable therapeutic options in select patients. In this review, we will discuss currently available pharmacologic therapies and describe promising drugs currently in development. We will also delve into the efficacy and safety concerns of splenectomy, splenic irradiation, and partial splenic artery embolization. Finally, we will propose a treatment algorithm to help guide clinicians in the management of symptomatic splenomegaly in patients with MF.
Topics: Embolization, Therapeutic; Humans; Primary Myelofibrosis; Protein Kinase Inhibitors; Spleen; Splenectomy; Splenic Artery; Splenomegaly
PubMed: 32417942
DOI: 10.1007/s00277-020-04069-4 -
British Journal of Haematology Jun 2017Sickle cell disease (SCD) is a group of recessively inherited disorders of erythrocyte function that presents an ongoing threat to reducing childhood and adult morbidity... (Review)
Review
Sickle cell disease (SCD) is a group of recessively inherited disorders of erythrocyte function that presents an ongoing threat to reducing childhood and adult morbidity and mortality around the world. While decades of research have led to improved survival for SCD patients in wealthy countries, survival remains dismal in low- and middle-income countries. Much of the early mortality associated with SCD is attributed to increased risk of infections due to early loss of splenic function. In the West, bacterial infections with encapsulated organisms are a primary concern. In sub-Saharan Africa, where the majority of infants with SCD are born, the same is true. However malaria presents an additional threat to survival. The search for factors that define variability in sickle cell phenotypes should include environmental modifiers, such as malaria. Further exploration of this relationship could lead to novel strategies to reduce morbidity and mortality attributable to infections. In this review, we explore the interactions between SCD, malaria and the spleen to better understand how splenomegaly and splenic (dys)function may co-exist in patients with SCD living in malaria-endemic areas.
Topics: Africa; Anemia, Sickle Cell; Endemic Diseases; Global Health; Humans; Malaria; Spleen; Splenomegaly
PubMed: 28493472
DOI: 10.1111/bjh.14592 -
Journal of the American Veterinary... May 2017OBJECTIVE To assess causes of splenomegaly and postsurgical outcomes in small-breed (ie, < 16-kg [< 35.2-lb]) dogs that underwent splenectomy and evaluate associations...
OBJECTIVE To assess causes of splenomegaly and postsurgical outcomes in small-breed (ie, < 16-kg [< 35.2-lb]) dogs that underwent splenectomy and evaluate associations among malignant disease, hemoperitoneum, and survival time in these patients. DESIGN Retrospective case series. ANIMALS 45 client-owned dogs. PROCEDURES Medical records of 2 veterinary facilities were reviewed to identify small-breed dogs that underwent splenectomy and had a histologic diagnosis recorded. Data analyzed included signalment, diagnosis, presence or absence of hemoperitoneum, and survival time. RESULTS 21 dogs had malignant neoplasia and 24 had benign splenic diseases. Hemangiosarcoma was the most common malignancy (14/21 [67%] dogs) and lymphoid nodular hyperplasia, hematoma, or extramedullary hematopoiesis (alone or in combination) was most commonly diagnosed in dogs with benign disease (17/24 [71%]). Wheaton Terriers were significantly more likely to have malignant splenic disease than were dogs of other breeds. Malignant splenic disease and the presence of hemoperitoneum had significant negative associations with survival time. Malignant disease was not significantly associated with the presence of hemoperitoneum. CONCLUSIONS AND CLINICAL RELEVANCE Causes for splenomegaly and survival times were similar to those previously reported for populations that primarily included large-breed dogs. There were approximately equal numbers of benign and malignant causes for splenomegaly in this population. Results suggested that Wheaton Terriers with splenomegaly had a higher likelihood of malignant neoplasia than other breeds and that hemoperitoneum may not be a significant predictor of malignancy in small-breed dogs. However, further research including a larger number of dogs is needed to confirm these findings. (J Am Vet Med Assoc 2017;250:1148-1154).
Topics: Animals; Colorado; Dog Diseases; Dogs; Female; Male; Medical Records; New York; Pedigree; Postoperative Complications; Retrospective Studies; Splenectomy; Splenic Diseases; Splenomegaly; Survival Analysis; Treatment Outcome
PubMed: 28467747
DOI: 10.2460/javma.250.10.1148 -
BMJ Case Reports Jul 2013
Topics: Adult; Humans; Leukemia, Hairy Cell; Male; Splenomegaly
PubMed: 23897391
DOI: 10.1136/bcr-2013-200515 -
CMAJ : Canadian Medical Association... Mar 2013
Topics: Humans; Hypertension, Portal; Liver Cirrhosis, Alcoholic; Male; Middle Aged; Nail Diseases; Sensitivity and Specificity; Splenomegaly
PubMed: 22927514
DOI: 10.1503/cmaj.120269 -
Disease Markers 2023Patients with cirrhosis and splenomegaly often have coagulation dysfunction which affects treatment and prognosis. This study explores the status, grading, and treatment...
OBJECTIVE
Patients with cirrhosis and splenomegaly often have coagulation dysfunction which affects treatment and prognosis. This study explores the status, grading, and treatment strategies of coagulation dysfunction in patients with liver cirrhosis and splenomegaly.
METHODS
A retrospective cohort study was conducted on the clinical data on consecutive patients with cirrhosis and splenomegaly treated at Hainan General Hospital, China, from January 2000 to December 2020. Starting research in January 2022.
RESULTS
Among 1522 patients included into this study, 297 (19.5%) patients had normal results in all five coagulation tests (prothrombin time, prothrombin activity, activated partial thromboplastin time, thrombin time, and fibrinogen), and 1225 (80.5%) had coagulation dysfunction in at least one of these tests. There were significant differences ( < 0.05) in treatment efficacy on these patients for three of these five coagulation tests, with the exception of prothrombin activity and thrombin time. When coagulation dysfunction was classified into grades I, II, and III based on scores from the three significant coagulation tests, prothrombin time, activated partial thromboplastin time, and fibrinogen, significant differences in surgical outcomes were found among the three grades of coagulation dysfunction and between grades I and III ( < 0.05). The operative mortality rate in patients with grade III in treating liver cancer, portal hypersplenism, and/or splenomegaly was 6.5%. There was no significant difference between patients with grades I and II ( > 0.05).
CONCLUSIONS
Approximately, 80% of patients with liver cirrhosis and splenomegaly had coagulation dysfunction. Surgery is feasible for grade I and II patients. For grade III patients, nonsurgical treatment should be given first, and surgery should only be considered when the coagulation function returns to normal or near-normal levels after treatment. This trial is registered with MR-46-22-009299.
Topics: Humans; Retrospective Studies; Splenomegaly; Prothrombin; Liver Cirrhosis; Fibrinogen; Blood Coagulation Disorders
PubMed: 37325552
DOI: 10.1155/2023/5560560