-
Journal of Nippon Medical School =... 2023As liver disease progresses, intrahepatic vascular resistance increases (backward flow theory of portal hypertension) and collateral veins develop. Adequate portal... (Review)
Review
As liver disease progresses, intrahepatic vascular resistance increases (backward flow theory of portal hypertension) and collateral veins develop. Adequate portal hypertension is required to maintain portal flow into the liver through an increase in blood flow into the portal venous system (forward flow theory of portal hypertension). The splenic artery resistance index is significantly and selectively elevated in cirrhotic patients. In portal hypertension, a local hyperdynamic state occurs around the spleen. Splenomegaly is associated with a poor prognosis in cirrhosis and is caused by spleen congestion and by enlargement and hyperactivation of splenic lymphoid tissue. Hypersplenism can lead to thrombocytopenia caused by increased sequestering and breakdown of platelets in the spleen. The close relationship between the spleen and liver is reflected in the concept of the hepatosplenic axis. The spleen is a regulatory organ that maintains portal flow into the liver and is the key organ in the forward flow theory of portal hypertension. This review summarizes the literature on the role of the spleen in portal hypertension.
Topics: Humans; Hypertension, Portal; Splenomegaly; Hypersplenism; Liver Cirrhosis; Portal Vein
PubMed: 36908126
DOI: 10.1272/jnms.JNMS.2023_90-104 -
Expert Opinion on Drug Safety Jan 2024Polycythemia Vera (PV) is a chronic myeloproliferative neoplasm hallmarked by deregulated proliferation of hematopoietic stem cells leading to prevalent expansion of red... (Review)
Review
INTRODUCTION
Polycythemia Vera (PV) is a chronic myeloproliferative neoplasm hallmarked by deregulated proliferation of hematopoietic stem cells leading to prevalent expansion of red cell mass, increased rate of vascular events, splenomegaly, disease-associated symptoms, and risk of evolution to secondary myelofibrosis and blast phase. PV is pathogenetically associated with autonomously persistent activation of JAK2, which causes overproduction of blood cells and an inflammatory condition responsible for the clinical manifestations of the disease. Extensively supported by preclinical studies, targeting JAK2-dependent signaling represents a rational therapeutic approach to PV, finally leading to the approval of ruxolitinib, a JAK1/2 inhibitor.
AREAS COVERED (LITERATURE RESEARCH)
We analyzed reports of phase 2 and phase 3 trials with ruxolitinib in PV and relevant literature dealing with efficacy and safety aspects, including most recent real-world reports.
EXPERT OPINION
Ruxolitinib is the only JAK2 inhibitor approved for the treatment of PV with well-known efficacy for splenomegaly, symptoms, and potentially reduction of vascular events. The treatment regimen is notably manageable and safe, with the most prevalent side effects primarily encompassing myelosuppression, hyperlipidemia, non-melanoma skin cancer and infections, mainly reactivation of Herpes Zoster. These effects necessitate ongoing surveillance and proactive preventive measures.
Topics: Humans; Polycythemia Vera; Splenomegaly; Nitriles; Pyrimidines; Janus Kinase Inhibitors; Pyrazoles
PubMed: 38156903
DOI: 10.1080/14740338.2023.2299391 -
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 -
BMC Pregnancy and Childbirth Mar 2023The spleen is a lymphopoietic organ, contains almost one quarter of the body's lymphocytes.
BACKGROUND
The spleen is a lymphopoietic organ, contains almost one quarter of the body's lymphocytes.
METHOD
This was a prospective cross sectional study, carried out at Kassala hospital, Sudan between 1st of May 2019 to 30th of April 2020. The objective of this study was to investigate the outcome of pregnancy in women with splenomegaly. A total coverage of 57 women with splenomegaly were approached among all pregnant women attending the hospital and asking for care. An enlarged spleen detected by palpation and subcategorized into mild, moderate and severe one according to its length below the left costal margin using Ultrasound. Data was collected using structured questionnaire. Means and proportions were compared between the groups of the study-using student and x test, and P < 0.05 was considered significant.
RESULTS
The most predominant type of splenomegaly was massive (50.9%) splenomegaly. The reported obstetric complications among the investigated women include: intrauterine growth restriction (19.3%), preterm labor ((17.5%), miscarriage (12.3%) and stillbirth (3.5%). Out of 50 patients their pregnancy progressed to delivery, three patients developed primary hemorrhage requiring blood transfusion with ≥ 2 units of blood. Respiratory distress syndrome (RDS), acute tachypnea of the newborn and stillborn babies were observed in 18%, 6% and 4% respectively. Higher proportion of women with poor obstetric outcomes was reported in cases of massive splenomegaly in comparison with other types.
CONCLUSION
The study showed significant association between adverse obstetric outcomes and massive splenomegaly. Thus, it is important to consider splenomegaly as one of the factors making the pregnancy high-risk one.
Topics: Pregnancy; Infant; Infant, Newborn; Humans; Female; Splenomegaly; Cross-Sectional Studies; Prospective Studies; Spleen; Abortion, Spontaneous
PubMed: 36870967
DOI: 10.1186/s12884-023-05465-0 -
Rheumatology International Jul 2020Felty's syndrome (FS) is a deforming disease, characterized by the triad of rheumatoid arthritis (RA), neutropenia, and splenomegaly. Currently, FS patients are treated... (Review)
Review
Felty's syndrome (FS) is a deforming disease, characterized by the triad of rheumatoid arthritis (RA), neutropenia, and splenomegaly. Currently, FS patients are treated mainly with immunosuppressants, such as methotrexate and glucocorticoids, which however are not suitable to some patients and may cause severe side effects. Here we report a clinical FS case that was treated with Tocilizumab (TCZ) successfully. The patient had symmetrical swelling and pain of multiple joints, deformity of elbow joints with obvious morning stiffness. Joint color Doppler ultrasound showed synovial hyperplasia and bone erosion of wrist and proximal interphalangeal joints and CT scan suggested splenomegaly. Further examination showed neutropenia and anemia, a high titer of anti-cyclic citrullinated peptide antibody, rheumatoid factor and anti-nuclear antibodies, positive p-ANCA, and elevated IgA and IgG. After treating with TCZ, the patient has been relieved of clinical symptoms. His spleen has recovered to normal size. The absolute neutrophil count (ANC) tended to be stable, and joint erosion did not deteriorate. We have reviewed the literatures on FS treatment with biological agents and found only a few reports using TNF-α antagonist and rituximab treating FS, but none with TCZ. So, it is the first time to report a successful FS case treated with TCZ. This case suggests that the TCZ may be a new choice for FS treatment, under the condition of closely monitoring the ANC.
Topics: Aged; Anti-Citrullinated Protein Antibodies; Antibodies, Antineutrophil Cytoplasmic; Antibodies, Antinuclear; Antibodies, Monoclonal, Humanized; Antirheumatic Agents; Axilla; Felty Syndrome; Humans; Leflunomide; Lymphadenopathy; Male; Methotrexate; Remission Induction; Rheumatoid Factor; Splenomegaly; Treatment Outcome
PubMed: 32347340
DOI: 10.1007/s00296-020-04588-3 -
La Revue Du Praticien Apr 2020Gaucher disease. Gaucher disease is a rare lysosomal autosomal recessive disease, caused by a deficiency of glucocerebrosidase, a lysosomal enzyme. The most frequent... (Review)
Review
Gaucher disease. Gaucher disease is a rare lysosomal autosomal recessive disease, caused by a deficiency of glucocerebrosidase, a lysosomal enzyme. The most frequent symptoms are cytopenia, splenomegaly, hepatomegaly, and potentially severe bone involvement (bone infarcts, avascular osteonecrosis, and pathological fractures). Neurological involvement may occur in type 2 and type 3 Gaucher disease. Patients with type 1 Gaucher disease have an increased risk of Parkinson disease, some solid cancers, and some hematologic malignancies including multiple myeloma. Patients often experience delays before their disease is being diagnosed. Thus, there is a need for physicians to recognize Gaucher disease symptoms to reduce the risk of irreversible complications.
Topics: Bone and Bones; Gaucher Disease; Glucosylceramidase; Humans; Parkinson Disease; Splenomegaly
PubMed: 32877100
DOI: No ID Found -
PloS One 2020Haematological toxicities occur in patients receiving oxaliplatin. Mild anaemia (grade 1-2) is a common side effect and approximately 90% of recipients develop...
PURPOSE
Haematological toxicities occur in patients receiving oxaliplatin. Mild anaemia (grade 1-2) is a common side effect and approximately 90% of recipients develop measurable spleen enlargement. Although generally asymptomatic, oxaliplatin-induced splenomegaly is independently associated with complications following liver resection for colorectal liver metastasis and separately with poorer patient outcomes. Here, we investigated oxaliplatin-induced haematological toxicities and splenomegaly in mice treated with escalating dosages comparable to those prescribed to colorectal cancer patients.
METHODS
Blood was analysed, and smears assessed using Wright-Giemsa staining. Paw coloration was quantified as a marker of anaemia. Spleen weight and morphology were assessed for abnormalities relating to splenomegaly and a flow cytometry and multiplex cytokine array assessment was performed on splenocytes. The liver was assessed for sinusoidal obstructive syndrome.
RESULTS
Blood analysis showed dose dependent decreases in white and red blood cell counts, and significant changes in haematological indices. Front and hind paws exhibited dose dependent and dramatic discoloration indicative of anaemia. Spleen weight was significantly increased indicating splenomegaly, and red pulp tissue exhibited substantial dysplasia. Cytokines and chemokines within the spleen were significantly affected with temporal upregulation of IL-6, IL-1α and G-CSF and downregulation of IL-1β, IL-12p40, MIP-1β, IL-2 and RANTES. Flow cytometric analysis demonstrated alterations in splenocyte populations, including a significant reduction in CD45+ cells. Histological staining of the liver showed no evidence of sinusoidal obstructive syndrome but there were signs suggestive of extramedullary haematopoiesis.
CONCLUSION
Chronic oxaliplatin treatment dose dependently induced haematological toxicity and splenomegaly characterised by numerous physiological and morphological changes, which occurred independently of sinusoidal obstructive syndrome.
Topics: Animals; Cytokines; Dose-Response Relationship, Drug; Hematologic Tests; Liver; Male; Mice; Organ Size; Oxaliplatin; Phenotype; Spleen; Splenomegaly; Time Factors
PubMed: 32877416
DOI: 10.1371/journal.pone.0238164 -
Clinics in Liver Disease Nov 2019Idiopathic portal hypertension (IPH) and extrahepatic portal venous obstruction (EHPVO) are prototype noncirrhotic causes of portal hypertension (PHT), characterized by... (Review)
Review
Idiopathic portal hypertension (IPH) and extrahepatic portal venous obstruction (EHPVO) are prototype noncirrhotic causes of portal hypertension (PHT), characterized by normal hepatic venous pressure gradient, variceal bleeds, and moderate to massive splenomegaly with preserved liver synthetic functions. Infections, toxins, and immunologic, prothrombotic and genetic disorders are possible causes in IPH, whereas prothrombotic and local factors around the portal vein lead to EHPVO. Growth failure, portal biliopathy, and minimal hepatic encephalopathy are long-term concerns in EHPVO. Surgical shunts and transjugular intrahepatic portosystemic shunt resolve the complications secondary to PHT. Meso-Rex shunt is now the standard-of-care surgery in children with EHPVO.
Topics: Animals; Biliary Tract Diseases; Disease Management; Disease Models, Animal; Disease Progression; Esophageal and Gastric Varices; Gastrointestinal Hemorrhage; Growth Disorders; Hepatic Encephalopathy; Humans; Hypertension, Portal; Liver Cirrhosis; Liver Transplantation; Metabolomics; Pancytopenia; Portal Vein; Portasystemic Shunt, Surgical; Portasystemic Shunt, Transjugular Intrahepatic; Quality of Life; Splenomegaly; Transcriptome; Venous Thrombosis; Idiopathic Noncirrhotic Portal Hypertension
PubMed: 31563222
DOI: 10.1016/j.cld.2019.07.006 -
Digestive and Liver Disease : Official... Apr 2021
Topics: Abdominal Pain; Acute Pain; Adult; Female; Humans; Splenomegaly; Tomography, X-Ray Computed; Wandering Spleen
PubMed: 32646735
DOI: 10.1016/j.dld.2020.06.025 -
Hematology. American Society of... Dec 2023Myeloproliferative neoplasms (MPNs) are characterized by clonal myeloproliferation in 1 or more of the hematopoietic stem cell lineages. Primary myelofibrosis (MF),...
Myeloproliferative neoplasms (MPNs) are characterized by clonal myeloproliferation in 1 or more of the hematopoietic stem cell lineages. Primary myelofibrosis (MF), post-polycythemia vera MF, and post-essential thrombocythemia MF have the worst prognosis and are characterized by the presence of cytokine-mediated symptom complex, splenomegaly, progressive marrow failure, and clonal instability, leading to leukemic transformation. The key therapeutic aims encompass the management of symptoms, splenomegaly, and anemia and the improvement of survivals. These therapeutic aims have evolved with the availability of Jak inhibitors and novel agents, making disease modification potentially achievable. Novel agents may potentially target MPN stem cells, epigenetic alterations, signaling pathways, and apoptotic pathways. In this case-based review, we outline our approach to the management of MF and discuss the therapeutic landscape of MF, highlighting the utility of Jak inhibitors and novel Jak inhibitor-based combinations.
Topics: Humans; Primary Myelofibrosis; Splenomegaly; Janus Kinase Inhibitors; Thrombocythemia, Essential; Myeloproliferative Disorders
PubMed: 38066870
DOI: 10.1182/hematology.2023000452