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Abstract Mesenteric vein thrombosis is generally difficult to diagnose and can be fatal. A case of extensive thrombosis of the mesenteric and portal veins was diagnosed early and successfully treated in a 26-year-old man with Down syndrome who was admitted to hospital because of abdominal pain, severe nausea and high fever. Ultrasonography revealed moderate ascites, and there was minimal flow in the portal vein (PV) on the Doppler examination. Computed tomography (CT) showed remarkable thickening of the walls of the small intestine and extensive thrombosis of the mesenteric, portal and splenic veins. Because neither intestinal infarction nor peritonitis was seen, combined thrombolysis and anticoagulation therapy without surgical treatment was chosen. Urokinase was administered intravenously and later through a catheter in the superior mesenteric artery. Heparin and antibiotics were given concomitantly. The patient's symptoms and clinical data improved gradually. After 10 days, CT revealed that collateral veins had developed and the thrombi in the distal portions of the mesenteric veins had dissolved, although the main trunk of the PV had not recanalized. The only risk factor of thrombosis that was detected was decreased protein S activity. [ABSTRACT FROM AUTHOR]