Veno-occlusive disease

SSRI Selective serotonin reuptake inhibitor VOD Veno-occlusive disease... 

Busulfan -alkylating agent -bone marrow suppression—can have prolonged nadir -ovarian suppression -seizures -hepatic veno-occlusive disease (VOD), particularly at BMT doses -interstitial pulmonary fibrosis -hyperpigmentation (particularly skin creases and nail beds)... 

Mitomycin C -antitumor antibiotic inhibits RNAand DNA synthesis -bone marrow suppression -nausea and vomiting—mild to moderate -mucocutaneous effects (mucositis, stomatitis, diarrhea) -vesicant if extravasated -nephrotoxicity -veno-occlusive disease (VOD) of the liver -hemolytic-uremic syndrome... 

Hepatic Effects. Severe cirrhosis of the liver was one of the primary systemic effects seen following injection of Thorotrast in humans (Baxter et al. 1980a, b Faber 1979 Kato and Kido 1987 Kato et al. 1983 Mori et al. 1979, 1983a, b Rao et al. 1986 Van Kaick et al. 1983). Cases of fibrosis, veno-occlusive disease, and blood-filled cavities were also found in the livers of Thorotrast patients (da Silva Horta 1967a Dejgaard et al. 1984). The latency period for the appearance of the cirrhosis was not clear, but was probably comparable to the latency period for liver tumors (25-30 years) since the two effects were often found together. 

Dejgaard A, Krogsgaard K, Jacobsen M. 1984. Veno-occlusive disease and peliosis of the liver after Thorotrast administration. Virchows Archiv Pathol Anat 403 87-94. 

Cl) = 0.30 - 0.92] was offset by an increased risk of death in remission (OR = 2.22, 95% Cl = 1.20 - 4.14), mainly due to infections. Strikingly, 11% of patients in the 6-TG arm compared to less than 2% in the 6-MP arm developed non-fatal hepatic toxicity with features of veno-occlusive disease (VOD) characterized by symptoms including tender hepatomegaly, hyperbilirubinaemia with elevated aminotransferases, thrombocytopenia out of proportion to neutropenia, and portal hypertension. In 85% of affected 6-TG recipients, these symptoms were observed during maintenance or interim maintenance. Of interest, in patients randomized to 6-MP, hepatic toxicity was associated with intensification elements in which both treatment arms received exclusively 6-TG. 

Lennard L, Richards S, Cartwright CS et al. UK MRC/NCRl Childhood Leukaemia Working Party. The thiopurine methyltransferase genetic polymorphism is associated with thioguanine-related veno-occlusive disease of the liver in children with acute lymphoblastic leukemia. Clin Pharmacol Ther 2006 80 375-383. 

Occasionally toxic compounds can directly damage the hepatic sinusoids and capillaries. One such toxic compound is monocrotaline, a naturally occurring pyrrolozidine alkaloid, found in certain plants (Heliotropium, Senecio, and Crotolaria species). Monocrotaline (Fig. 7.7) is metabolized to a reactive metabolite, which is directly cytotoxic to the sinusoidal and endothelial cells, causing damage and occlusion of the lumen. The blood flow in the liver is therefore reduced and ischemic damage to the hepatocytes ensues. Centrilobular necrosis results, and the venous return to the liver is blocked. Hence, this is known as veno-occlusive disease and results in extensive alteration in hepatic vasculature and function. Chronic exposure causes cirrhosis. 

Palmer SM, Robinson LJ, Wang A, Gossage JR, Bashore T, Tapson VF. Massive pulmonary edema and death after prostacyclin infusion in a patient with pulmonary veno-occlusive disease. Chest 1998 l 13(1 ) 237 10. 

The incidence of hepatic veno-occlusive disease in 249 consecutive women treated with norethisterone who... 

Hagglund H, Remberger M, Klaesson S, LonnqvisL B, Ljungman P, Ringden O. Norethisterone treatment, a major risk-factor for veno-occlusive disease in the liver after allogeneic bone marrow transplantation. Blood 1998 92(12) 4568-72. 

Two outbreaks of human liver disease in India have been attributed to the consumption of plants containing pyrrolizidine alkaloids. In the first instance, the disease was caused by eating cereals contaminated with seeds of a Crotalaria species.56 Haemodynamic studies were carried out on eight patients suffering from the characteristic veno-occlusive disease. In the second study, two cases of sudden liver failure that are believed to be due to the ingestion of herbal concoctions made from seeds and plants of Heliotropium species are reviewed.57... 

FLichardson PG, Elias AD, Krishnan A, et al. Treatment of severe veno-occlusive disease with defibrotide compassionate use results in response without significant toxicity in a high risk population. Blood 1998 92 737-744. 

SPERL, W., STUPPNER, H., GASSNER, I., JUDMAIER, W., DEETZE, O., VOGEL, W., Reversible hepatic veno-occlusive disease in an infant after consumption of pyrrolizidine-containing herbal tea., Eta. J. Pediatr., 1995, 154, 112-116. 

ZUCKERMAN, M STEENKAMP, V., STEWART, M.J., Hepatic veno-occlusive disease as a result of a traditional remedy confirmation of toxic pyrrolizidine alkaloids as the cause, using an in vitro technique., J. Clin. Pathol., 2002, 55, 676-679. 

Veno-occlusive disease Azathioprine, dactinomycin, dacarbazine, cyclophosphamide... 

Veno-occlusive disease (VOD) differs from Budd-Chiari syndrome in that it consists of occlusive fibrosis of the small intrahepatic veins. VOD may present as either an acute form with sudden ascites, liver enlargement and rapidly rising bilirubin, or as a chronic form with fibrosis and cirrhosis. One of the main causes of VOD is the use of cyclophosphamide or alkalating agents during conditioning for bone marrow transplantation, where it occurs in up to 20% of cases. Other causes include irradiation, antineoplastic drugs, pyrrolizidine alkaloids and alcohol. 

Herbal medicines are becoming more and more popular, and indeed some herbal products may be considered to benefit people with liver disease, e.g. Silybum marianum (milk thistle), Picrorhiza kurroa, Phyllanthus, etc. Herbal hepatotoxicity is increasingly being recognised, for example, with kava kava, black cohosh, and many traditional Chinese remedies. The range of liver injury includes minor transaminase elevations, acute and chronic hepatitis, steatosis, cholestasis, zonal or diffuse hepatic necrosis, veno-occlusive disease and acute liver failure. In addition to the potential for hepatotoxicity, herb-drug interactions may affect the safety and efficacy of concurrent medical therapy [15]. 

Busulfan Nausea and vomiting rarely diarrhoea Bone marrow depression pulmonary infiltrates and fibrosis alopecia gynaccomasiia ovarian failure hyperpigmentation azoospermia leukaemia chromosome aberrations cataracts hepatitis seizures and veno-occlusive disease with high doses... 

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