Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0019209 (hepatomegaly)
 5,798 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hepatic veno-occlusive disease (VOD) is the most common life threatening complication of preparative-regimen-related toxicity for bone marrow transplantation (BMT). The frequency of VOD varies greatly, from 1-2% in centers performing pediatric BMT for thalassemia to over 50% in some centers doing BMT for hematologic malignancy. The term liver toxicity syndrome is a clinicopathologic definition which encompasses the range of histopathology within the hepatic venules and surrounding sinusoids and hepatocytes. These histologic abnormalities are statistically associated with a clinical syndrome of jaundice, ascites, and painful hepatomegaly developing early post-transplant. Newer modalities which may aid accuracy are transvenous liver biopsy along with determination of the gradient between the wedged and free hepatic venous pressures, and measurement of blood coagulatory components, particularly protein C levels. Analyses of clinical risk factors for VOD are confounded by lack of a clear hierarchy of risk when comparing heterogeneous patient populations, the methods of patient selection and choice of controls, and whether analysis is univariate or multivariate. Prospective multivariate analyses indicate that the risk of developing liver toxicity is independently correlated with intensity of conditioning therapy, pre-transplant viral hepatitis, use of antimicrobial therapy with acyclovir, amphotericin, or vancomycin (reflecting fever), and mismatched or unrelated allogeneic marrow grafts. These analyses plus morphologic and biochemical data support the hypothesis that VOD is caused by cytoreductive injury to hepatocytes and endothelium in zone three of the liver acinus, and in turn strongly influenced by factors which induce the release of tumor necrosis factor-alpha (TNF-alpha) leading to enhancement or activation of coagulation with obstruction of hepatic sinusoids and venules. Pharmacokinetic measurements of busulfan as a conditioning agent demonstrate a correlation between high steady-state busulfan levels and liver toxicity and suggest that safer and/or more efficacious plasma busulfan concentrations can be obtained by making individual dose adjustments and by changing the schedule of administration. Conservative therapy of severe VOD, including the use of peritoneal-pleural shunts for relief of ascites, is unsatisfactory. Results from prophylactic studies aimed at preventing VOD by heparin or prostaglandin E1 indicate considerable differences with toxicity and efficacy. Use of the TNF-alpha blocker, pentoxifylline, has also shown promise in lessening VOD. A statistical model which predicts patients likely to have an unfavorable outcome from VOD has been used to select premorbid patients for promising new therapeutic modalities, such as recombinant tissue plasminogen activator.
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PMID:Hepatic veno-occlusive disease--liver toxicity syndrome after bone marrow transplantation. 142 75

A 15-month-old boy with severe aplastic anemia developed veno-occlusive disease (VOD) after allogeneic bone marrow transplantation (BMT), in which the preparative regimen included 50 mg/kg/day cyclophosphamide and anti-lymphocyte globulin for 4 consecutive days. The diagnosis was made based on clinical symptoms and data including, hepatomegaly, right upper quadrant abdominal pain, jaundice, ascites, coagulopathy and thrombocytopenia which was refractory to transfusions of platelet concentrate. We gave 2, 3, 5 and 5 mg/day/body of recombinant tissue plasminogen activator (tPA) followed by heparin and prostaglandin E1 (PGE1) effectively and without significant side effect on days 9, 10, 13 and 14, respectively. Clinical and biochemical improvement was steady and dramatic. We suggest that tPA following continuous heparin and PGE1 infusion may be useful in the treatment of VOD even in infantile cases.
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PMID:Successful treatment of an infant with veno-occlusive disease developed after allogeneic bone marrow transplantation by tissue plasminogen activator, heparin and prostaglandin E1. 763 94

The pathogenesis of veno-occlusive disease (VOD) of the liver appears to be secondary to endothelial damage of terminal hepatic venules, which leads to activation of the coagulation cascade, fibrin deposition, and eventual fibrous obliteration of the hepatic venules. Patients with VOD usually present with jaundice, hepatomegaly, weight gain, and ascites. This complication is usually associated with a high mortality rate. We report here the frequency and treatment of VOD in our autologous bone marrow transplant (BMT) patient population. Three of 15 (20%) children (median age 9 years) developed VOD and were treated with recombinant tissue plasminogen activator (rt-PA). Two of these three patients were prepared for BMT with busulfan (16 mg/kg) and cyclophosphamide (Cytoxan, 200 mg/kg), while the other child received cytosine arabinoside (ARA-C 18 g/m2), Cytoxan (3,600 mg/m2) and total body irradiation (TBI, 1,400 y). VOD developed between days 7-24 posttransplant. Clotting studies obtained pretransplant and during VOD included prothrombin time (PT), partial thromboplastin time (PTT), fibrinogen, fibrin-degradation product (FDP), proteins C and S, and platelet count. There was no correlation between the incidence of VOD and coagulation status. All patients had normal pretransplant clotting studies. However, protein C levels were noted to be consistently low for those patients at the time of VOD. All three patients received rt-PA at a dose of 0.25-0.5 mg/kg for 4 days. This dose produced increased levels of FDP but did not significantly prolong PT nor PTT. Two of the patients had dramatic responses and had complete resolution of VOD within 6-12 days from the start of therapy. The other patient died of fulminant hepatic failure. It seems that rt-PA is effective in VOD of the liver, which may be associated with low protein C level.
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PMID:Recombinant tissue plasminogen activator (rt-PA) for veno-occlusive liver disease in pediatric autologous bone marrow transplant patients. 819 48

Approximately two thirds of cases of hepatic flow obstruction are due to myeloproliferative disorders. Restoration of hepatic blood flow is the essential goal of treatment. Thrombolytic therapy seems to achieve good results at least in selected cases. A 32-year-old woman is presented, with an intermittent increase in platelet count (526-725 x 10(9)/L), two previous spontaneous abortions and acute symptomatic occlusion of hepatic veins, and in whom a diagnosis of essential thrombocythemia was initially carried out in agreement with the polycythemia vera study group criteria. She received recombinant tissue plasminogen activator followed by heparin with restoration of normal hepatic outflow. Asymptomatic re-occlusion of the hepatic veins was observed 1 year later, despite adequate continuous warfarin treatment. Angiography showed marked narrowing of the intrahepatic cava vein due to extrinsic compression by an enlarged liver, not due to a new thrombosis so that no specific intervention could be performed. In the presence of a dearly documented hepatic vein thrombosis, thrombolytic therapy should be considered. The patient was given low-molecular-weight heparin with a dramatic reduction in previously elevated fibrinogen level and a good control of the hepatic function.
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PMID:Thrombocytosis and recurrent hepatic outflow obstruction (Budd-Chiari syndrome) after successful thrombolysis: case report and literature review. 1251 87