Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0038002 (splenomegaly)
 9,873 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

There are several possible pathophysiological links between the development of pulmonary hypertension and myelofibrosis with myeloid metaplasia. We report a woman with myelofibrosis and myeloid metaplasia who presented with dyspnea and massive, painful splenomegaly. Right heart catheterization evidenced pulmonary hypertension. Her management consisted of splenic irradiation associated to sildenafil. Dyspnea in patients with myelofibrosis and myeloid metaplasia can be secondary to pulmonary hypertension and conversely the differential diagnosis of pulmonary hypertension should include a myeloproliferative syndrome.
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PMID:[Dyspnea secondary to pulmonary hypertension in a patient with splenic myeloid metaplasia]. 1967 18

Clinical care of patients with polycythemia vera, essential thrombocythemia and myelofibrosis (MF) requires not only a broad understanding of general treatment principles but also familiarity with the management of hydroxyurea-refractory disease complications. The latter include progressive splenomegaly, symptomatic portal hypertension (e.g. ascites, variceal bleeding), pulmonary hypertension, bone pain, intractable pruritus, constitutional symptoms (e.g. fatigue, night sweats) and cachexia (i.e. loss of lean body mass, general ill health, poor appetite). Some of these symptoms are directly or indirectly related to extramedullary hematopoiesis (EMH) and others to proinflammatory cytokine excess. Results from recent clinical trials of JAK inhibitors suggest remarkable activity in MF-associated constitutional symptoms, cachexia, pruritus and hydroxyurea-refractory splenomegaly. Involved-field radiotherapy is best utilized in the setting of EMH-associated symptoms, including ascites, bone (extremity) pain and pulmonary hypertension. Splenectomy is indicated in the presence of drug-refractory splenomegaly and frequent red cell transfusion requirement. Transjugular intrahepatic portosystemic shunt is used to alleviate symptoms of portal hypertension.
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PMID:Treatment options for hydroxyurea-refractory disease complications in myeloproliferative neoplasms: JAK2 inhibitors, radiotherapy, splenectomy and transjugular intrahepatic portosystemic shunt. 2052 7

The main cause of hepatosplenomegaly in primary (PMF), post polycythemia vera (post-PV MF), and post essential thrombocythemia (post-ET MF) myelofibrosis (MF) is extramedullary hematopoiesis (EMH). Drug-refractory symptomatic splenomegaly in MF is usually managed by splenectomy or involved-field radiotherapy. The latter is most effective in the treatment of MF-associated bone pain and pulmonary hypertension.Our previous experience with hepatosplenic radiotherapy in MF showed efficacy in the majority of treated patients but its utility was limited by the transient nature of its benefit and the occurrence of treatment-related pancytopenia. In an effort to address these issues,we have adopted an induction-maintenance treatment strategy that utilizes lower radiation doses-induction with 100 cGy total in four daily doses of 25 cGy and maintenance with either the same or lower intensity regimen. Herein, we report our most recent experience using this treatment plan in two cases, who in addition to their expected response from the standpoint of splenomegaly, also unexpectedly showed a marked response of their underlying accelerated phase disease,including clearance of circulating blasts and basophilia.
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PMID:Effective management of accelerated phase myelofibrosis with low-dose splenic radiotherapy. 2066 15

Portopulmonary hypertension (POPH) is a not infrequent but serious complication of liver cirrhosis. Continuous intravenous epoprostenol infusion is a treatment option for this condition. Progressive splenomegaly with pancytopenia (hypersplenism) is associated with epoprostenol use in POPH. After recognizing a case of epoprostenol-induced hypersplenism that resolved upon stopping the drug, the authors retrospectively reviewed all patients treated with epoprostenol at the center for both POPH and pulmonary hypertension due to other causes. Five of 11 patients with POPH developed hypersplenism secondary to epoprostenol. In 1 patient, and possibly in a second, the hypersplenism resolved upon discontinuation of epoprostenol. None of 9 patients with pulmonary hypertension due to other causes developed splenomegaly. This report confirms hypersplenism as a complication of epoprostenol therapy for POPH. Furthermore, the authors demonstrate for the first time that hypersplenism may be reversed by stopping the medication and propose a mechanism for this phenomenon.
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PMID:Epoprostenol-induced hypersplenism in portopulmonary hypertension. 2222 13

Beta-thalassaemia major is a genetic blood disorder caused by the reduced synthesis of beta globin chain. The consequences of the resulting chronic anaemia are also common and include growth retardation, bone marrow expansion, extramedular hematopoiesis, splenomegaly, increased intestinal iron absorption, susceptibility to infections, and hypercoagulability. Transfusional iron overload can affect heart function by directly damaging tissue through iron deposition or via iron-mediated effects at other sites. Cardiac dysfunction is common in patients with thalassaemia and is the leading cause of mortality. The main cardiac abnormalities reported in patients with thalassaemia major (TM) and iron overload are left ventricular systolic and diastolic dysfunction, pulmonary hypertension, valvulopathies, arrhythmias and pericarditis. These cardiac abnormalities are a consequence of the general co-morbid conditions in thalassaemia but are closely related to concomitant endocrine deficiencies, hypercoagulability state and inflammatory milieu. Iron's toxicity within cells arises from its capacity to catalyse the production of reactive oxygen species that cause lipid peroxidation and organelle damage, which lead ultimately to cell death and fibrosis. With the introduction of new technologies such as cardiac magnetic resonance T2* , the early detection of cardiac iron overload and associated cardiac dysfunction is now possible, allowing time for reversal through iron chelation therapy.
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PMID:Cardiovascular aspect of Beta-thalassaemia. 2223 92

Beta-thalassemia intermedia (TI) is associated with a variety of serious clinical complications that require proactive and comprehensive management. These include skeletal deformities and osteopenia, compensatory extramedullary hematopoiesis and tumor formation, progressive splenomegaly, a hypercoagulable state resulting in thromboembolic events and pulmonary hypertension, and increased gastrointestinal iron absorption that often results in nontransfusional iron overload and liver damage. Although TI is generally considered a non-transfusion-dependent thalassemia, transfusion therapy may be an important part of the comprehensive management of this disease. This review describes the current state of the art for medical management of TI, with particular focus on the roles of splenectomy, transfusion, and iron chelation therapy.
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PMID:Contemporary approaches to treatment of beta-thalassemia intermedia. 2263 Oct 38

Idiopathic myelofibrosis is a rare chronic myeloproliferative disease leading to extramedullary hematopoiesis (myeloid metaplasia) with splenomegaly. The liver and less frequently other organs including the lung can be involved, therefore portal hypertension is relatively common. Pulmonary hypertension (PH) is only occasionally reported, although recent studies have suggested an association between PH and myeloproliferative disorders.We present a case of PH diagnosis by echocardiography in a patient affected by idiopathic myelofibrosis with portal hypertension.
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PMID:Pulmonary hypertension diagnosed by echocardiography during idiopathic myelofibrosis. A case report and a brief review of the literature. 2295 26

Gaucher disease (GD), the most common inherited lysosomal storage disorder, is a multiorgan disease due to an autosomal recessive defect of the gene encoding glucocerebrosidase enzyme, responsible for the accumulation of glucosylceramide (glucocerebroside) into reticuloendothelial cells, particularly in the liver, spleen and bone marrow. GD is a clinically heterogeneous disorder and it is conventionally classified in type 1 (non-neuronopathic disease), types 2 and 3 (acute and chronic neuronopathic disease, respectively). Features of clinical presentation and organ involvement as well as age, at presentation are highly variable among affected patients. Splenomegaly and/or thrombocytopenia are the most common presenting features either as incidental findings during routine blood count or physical examination. Other possible clinical manifestations can be hepatomegaly with abnormal liver function tests, bone pain often associated with skeletal complications (pathological fractures, avascular necrosis, osteopenia), pulmonary hypertension and, in neuronopathic forms, neurological manifestations (dysfunction of eye motility, mild mental retardation, behavioural difficulties, choreoathetosis and cramp attacks). For all these reasons GD diagnosis is often a real challenge for internists. In the presence of clinical suspicion of GD, the diagnosis has to be confirmed measuring the betaglucocerebrosidase activity in the peripheral leukocytes and by molecular analysis. Each patient needs an accurate initial multisystemic assessment, staging the damage of all the possible organs involved, and the burden of the disease, followed by regular followup. The correct and early diagnosis permits to treat patients properly, avoiding the complications of the disease.
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PMID:Gaucher disease: a diagnostic challenge for internists. 2409 Jul 39

Myelofibrosis (MF) is a rare chronic BCR-ABL1 (breakpoint cluster region-Abelson murine leukemia viral oncogene homologue 1)-negative myeloproliferative neoplasm characterized by progressive bone marrow fibrosis, inefficient hematopoiesis, and shortened survival. The clinical manifestations of MF include splenomegaly, consequent to extramedullary hematopoiesis, cytopenias, and an array of potentially debilitating abdominal and constitutional symptoms. Dysregulated Janus kinase (JAK)-signal transducer and activator of transcription signaling underlies secondary disease-associated effects in MF, such as myeloproliferation, bone marrow fibrosis, constitutional symptoms, and cachexia. Common fatal complications of MF include transformation to acute leukemia, thrombohemorrhagic events, organ failure, and infections. Potential complications from hepatosplenomegaly include portal hypertension and variceal bleeding, whereas extramedullary hematopoiesis outside the spleen and liver - depending on the affected organ - may result in intracranial hypertension, spinal cord compression, pulmonary hypertension, pleural effusions, lymphadenopathy, skin lesions, and/or exacerbation of abdominal symptoms. Although allogeneic stem cell transplantation is the only potentially curative therapy, it is suitable for few patients. The JAK1/JAK2 inhibitor ruxolitinib is effective in improving splenomegaly, MF-related symptoms, and quality-of-life measures. Emerging evidence that ruxolitinib may be associated with a survival benefit in intermediate- or high-risk MF suggests the possibility of a disease-modifying effect. Consequently, ruxolitinib could provide a treatment backbone to which other (conventional and novel) therapies may be added for the prevention and effective management of specific MF-associated complications.
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PMID:Myelofibrosis-associated complications: pathogenesis, clinical manifestations, and effects on outcomes. 2450 43

In thalassaemic patients, multiple organ systems may be affected by the disease, blood transfusion, iron overload and chelating therapy. Patients may develop cardiomyopathy, pulmonary hypertension or heart failure requiring pre-operative echocardiography or cardiac catheterisation. Restrictive lung dysfunction is commonly encountered, especially in patients with splenomegaly. Haemoglobin level should be optimised pre-operatively and maintained at adequate levels with transfusion and blood-saving strategies. Susceptibility to infections should be managed with broad-spectrum antibiotics. Thromboembolic events due to hypercoagulability should be prevented by simple measures, such as graduated compression stockings, intermittent pneumatic compression and early mobilisation, and possibly anticoagulant drugs. When general anaesthesia is administered, the risk of difficult intubation due to oro-facial malformation should be considered. Cardiovascular depression due to negative inotropic and vasodilating effects of general anaesthesia should be minimised. Neuraxial techniques may also be challenging due to spinal skeletal abnormalities and extramedullary haemopoiesis. A multidisciplinary pre-operative approach, clinical optimisation and a carefully planned strategy are mandatory.
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PMID:A narrative review of peri-operative management of patients with thalassaemia. 2460 13


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