Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019214 (hepatosplenomegaly)
 4,408 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The authors have identified six Southeast Asian patients ranging in age from 14 to 21 years with hemoglobin E-beta(0) thalassemia and a coagulopathy involving von Willebrand factor (vWF). These patients had normal or only slightly decreased plasma clotting factor levels. The activated partial thromboplastin time was prolonged in four of the patients. The abnormal feature common to all patients was a qualitative loss of high molecular weight multimers of vWF by crossed immunoelectrophoresis (vWF:CIE). Plasma vWF antigen concentration (vWF:Ag) and ristocetin cofactor activity (vWF:RCo) also were decreased and bleeding time prolonged in three patients. Epistaxis was present in two. No family history of increased bleeding tendency was present in any patient. Coagulation parameters and vWF:CIE were normal in two first-degree relatives without this hemoglobinopathy. vWF abnormalities and clinical manifestations were greatest in those patients with the most severe anemia and hepatosplenomegaly. These six patients appear to have an acquired abnormality of vWF, although they lack the clinical characteristics of acquired von Willebrand disease. While the etiology of this abnormality is unclear, the authors speculate that proteolysis of vWF secondary to extramedullary hematopoiesis or loss through high cardiac output shear stress in these anemic patients may be involved.
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PMID:Abnormality of von Willebrand factor in patients with hemoglobin E-beta (0) thalassemia. 210 77

Trisomy 21 was diagnosed by prenatal blood sampling at 30 and 31 weeks of gestation, respectively, in two fetuses with hepatosplenomegaly. In both, the fetal blood contained blast cells and cells showing megakaryocytic differentiation. Case 1 died neonatally 1 week later and the cellular infiltration causing enlargement of liver and spleen had a megakaryocytic/megakaryoblastic component staining positively for von Willebrand factor and binding to Ulex europaeus 1. Case 2, when stillborn 4 weeks later, had remarkably severe hepatic and pancreatic fibrosis. Cells in pulmonary vessels had morphology and immunohistochemical reactions consistent with megakaryocytic/megakaryoblastic differentiation. Comparison of the two cases suggests that the visceral fibrosis of perinatal Down syndrome may progress very rapidly in utero. They demonstrate further the association of the fibrosis with a dyshemopoiesis in which there is proliferation of cells of megakaryocytic lineage and a close relationship to the transient leukemia of neonatal Down syndrome.
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PMID:Fetal megakaryocytic dyshemopoiesis in Down syndrome: association with hepatic and pancreatic fibrosis. 750 58

We report three infants with Down syndrome who had hepatic fibrosis, which is rare in this syndrome. Liver specimens were obtained by biopsy or autopsy. In one patient, the peripheral blood contained blastoid cells, a typical hematological feature of the transiently abnormal myelopoiesis of Down syndrome. Ascites and hepatosplenomegaly were found in all patients. The intralobular hepatic fibrosis was pericellular and perisinusoidal, and the narrowing of the central veins resembled that in venoocclusive disease of the liver. We found some megakaryocytes in the liver, which were stained for von Willebrand factor and platelet glycoprotein IIb/IIIa. In one specimen, collagen type IV and alpha smooth muscle actin were stained by immunohistochemical methods, so the fibrosis in this case was probably caused by cells such as Ito cells derived from myofibroblasts. Overall, the findings suggest that megakaryocytes in the liver of these three patients produce collagen-stimulating cytokines such as transforming growth factor beta, and that Ito cells were involved in the hepatic fibrosis we observed.
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PMID:[Unusual hepatic fibrosis in three cases of Down syndrome]. 875 40

A 9-year-old-boy with severe haemophilia A (factor VIII < 1%) developed colicky abdominal pain with swelling in the left iliac fossa for 4 weeks. His LDH level was 1423 IU/l (normal range < 220 IU/l) and his uric acid, 6.8 mg/dl. A computerised tomography (CT) scan of the abdomen demonstrated a tumour of the terminal ileum and mild hepatosplenomegaly. Pre-operative screening for factor VIII inhibitor was negative. Post-operatively, the patient needed high doses of factor VIII to maintain haemostasis. The tumour was found to be a high-grade lymphoma of Burkitt's type. He recovered from his operation and chemotherapy was commenced. Investigations demonstrated an anti-von Willebrand factor (VWF) antibody. He subsequently relapsed and died of progressive disease. Development of anti-VWF antibody in lymphoma is well known, but development of this antibody in a haemophilia A patient developing lymphoma has not been reported. The present case shows that antibody to VWF should be considered as a possible reason for an increased factor VIII requirement in such patients.
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PMID:Development of anti-VWF antibody in a patient with severe haemophilia A following the development of high-grade non-Hodgkin's lymphoma. 1206 87