Patients with inflammatory bowel disease can have hypercoagulability (1,2). Although some cases are idiopathic (as in this case), many patients with the combination of inflammatory bowel disease and deep vein thrombosis have documented abnormalities of a hypercoagulable state such as increased factors V and VII, thrombocytosis, or elevated thromboplastin III level (1,2). The commonly affected sites of thrombosis are veins of the lower extremities, pelvic veins, portal vein, cerebral veins, pulmonary veins, renal veins, and splenic vein (1,2). Hepatic vein thrombosis (Budd-Chiari Syndrome) has not been reported in children with inflammatory bowel disease (3-8). We report an adolescent with ulcerative colitis who developed Budd-Chiari Syndrome.
A 16-year-old boy was first diagnosed with ulcerative colitis at age 8 years, when he had bloody diarrhea, mouth sores, and poor growth (10th percentile). Laboratory data showed a sedimentation rate of 15 mm/h, a C-reactive protein (CRP) of less than 0.6 mg/dl, and a hemoglobin level of 11.5 g/dl. Results of a barium study of the esophagus, stomach, and small bowel were normal. A colonoscopy showed pancolitits with erythema, edema, and friability. These changes were confluent and continuous. Colonoscopic biopsies showed acute and chronic inflammation with crypt abscesses and no granulomas. He was treated with 30 mg of prednisone per day and 1 g of sulfasalazine twice a day. Clinical course through age 16 years was characterized by a persistent need for varying doses of steroids (from 5 mg every other day to 40 mg a day). (Fig. 1) He was also on maintenance sulfasalazine or mesalamine. He was admitted at age 10 years for management of an acute exacerbation. This exacerbation was responsive to parenteral steroids and was not associated with complications or blood transfusions.
At 16 years of age, he returned after 5 days of dull right upper quadrant abdominal pain and low-grade fever. He had been stable for the past 6 months on prednisone, 10 mg every other day and oral and rectal aminosalicylic acid (ASA) (Fig. 1). There was no history of vomiting, bleeding, bruising, mental status changes, anorexia, weight loss, or jaundice. Physical examination showed that the liver was tender and palpable 5 cm below the xiphoid, with enlargement of the left lobe. The spleen was not palpable. He did not have an abnormal venous pattern on the abdomen. There were no bruits. The abdomen was slightly distended, ascites could not be demonstrated. There was no edema of the legs.
The hemoglobin level was 10.2 g/dl. The leukocyte count was 11,200/dl with a normal differential. The platelet count was 413,000/dl. The prothrombin time was 14.5 seconds with the control of 11.8 seconds. The partial thromboplastin time was 26 seconds, (normal 20-35 seconds). The international normal ratio (INR) was 1.51 (normal 1.3). The total protein level was 5.9 g/dl (normal 6.5-8.5g/dl). The albumin level was 3.0 g/dl (normal 3.5-5.6g/dl). The liver enzymes were as follows: aspartate aminotransferase 66 U/L (5-30 U/L), alanine aminotransferase 245 U/L (5-40 U/L), gamma-glutamyl transferase 26 U/L (10-40), alkaline phosphatase 200 IU/L (34-113 IU/L). The bilirubin was 0.4 mg/dl (0.1-1.5 mg/dl), and the serum ammonia was 28 μM/L (0-60 μM/L). The serology results for hepatitis A, B, and C, and for cytomegalovirus and Epstein-Barr virus were negative. Blood levels for ceruloplasmin, anti-nuclear antibody, and anti-liver-kidney-microsomal antibody were normal. The results of the laboratory evaluation for factors leading to hypercoagulability were normal. (Table)
A computed tomography scan showed uneven density of the liver, with the relative central sparing typically seen in Budd-Chiari Syndrome (9). (Fig. 2) There was free fluid (ascites) present in the abdomen. A venogram showed occlusion of the right hepatic vein, a diminutive left hepatic vein, and the parenchymal stain and portal venous opacification characteristic of Budd-Chiari Syndrome (9). (Fig. 3)
A percutaneous liver biopsy showed central lobular vein thrombosis with focal atrophy of the perivenous hepatocytes. There was congestion of the sinusoids. (Fig. 4)
The radiologic and pathologic findings confirmed hepatic vein thrombosis. Therapeutic options included: angiographic thrombolysis with streptokinase or urokinase, systemic anti-coagulants, angioplasty, or portocaval shunt (8-21). Because he presented without liver failure, and with radiologic documentation of established collaterals, nonsurgical management with systemic anticoagulant therapy (heparin and warfarin) was initiated to prevent thrombus progression. Just before starting the anticoagulant therapy, he developed acute right subclavian vein thrombosis presumed to be caused by pretreatment clinically evident (but unproved) hypercoagulable state. This subclavian vein thrombosis resolved after 2 weeks on warfarin. The patient has been stable for 12 months after acute presentation. He remains on warfarin, Spironolactone, and furosemide. There is no clinical evidence for disease progression.
Budd-Chiari syndrome in childhood can present in an acute or chronic form (3-8) The acute syndrome is characterized by sudden onset of abdominal pain, distention, jaundice, hepatomegaly, ascites, and edema (3). Acute disease can progress on to hepatic failure, although that is uncommon in childhood (3-8). The chronic presentations are more typical, and can include symptoms similar to the acute form developing much more slowly over months or years. Visibly dilated abdominal veins and splenomegaly without encephalopathy have also been noted in the chronic form. This patient had the acute form (5).
Though the mechanism was not documented in this patient, the hypercoagulability associated with inflammatory bowel disease may have played an etiologic role (1,2). In one autopsy series, 39% of patients with ulcerative colitis were found on detailed examination to have evidence of venous thrombosis. The most common sites for venous thrombosis are the pulmonary vascular system, and the deep veins of the legs (5). Hepatic vein thrombosis complicating inflammatory bowel disease, although rare, is recognized (5-7). Budd-Chiari Syndrome in children overall is quite rare (7,8). Causes of hepatic vein obstruction in childhood include tumors, trauma, webbed inferior vena cava, parenteral nutrition, ventricular atrial shunt, surgical complications, sickle cell anemia, systemic lupus erythematosus, antiphospholipid antibody syndrome, and toxins, none of which were present in this patient (3,4).
Chesner reported two adults with ulcerative colitis and fatal Budd-Chiari syndrome (5). Brinson reported a 22-year-old woman with ulcerative colitis and Budd-Chiari syndrome who recovered (7). The association of fatal Budd-Chiari syndrome with Crohn's disease was recorded by Maccini (6) in a 35-year-old woman. Whitteman et al. reported an adult with Crohn's disease who developed intestinal obstruction as well as Budd-Chiari syndrome (21).
Therapeutic options for Budd-Chiari Syndrome (with or without inflammatory bowel disease) are varied with the clinical presentation and the etiology of the vein obstruction (8). Angiographic thrombolysis with streptokinase and urokinase and/or systemic anti-coagulants are used to treat acute hepatic vein thrombosis. Interventional radiologic procedures that can also be used in the acute form include conventional angioplasty, laser angioplasty, stent placement, and membranotomy (8,12,13). For chronic situations where hepatic vein thrombosis is more established, with associated cirrhosis and portal hypertension, surgical shunt procedures have been employed. Portocaval, mesocaval, portoatrial, mesoatrial, cavoatrial, meso-pulmonary vein, splenoatrial, mesoceliac and mesocavoatrial have all been used with variable success (8). More recently, angiographic transjugular intrahepatic portosystemic shunt (TIPS) has been used (12). In Budd-Chiari associated liver failure, hepatic transplantation may be a lifesaving procedure (15).
In summary, we report the youngest patient with inflammatory bowel disease and acute Budd-Chiari syndrome. This patient has been stable for 12 months without surgery or TIPS and remains on anticoagulation therapy. Budd-Chiari syndrome (hepatic vein thrombosis) can occur in childhood inflammatory bowel disease (presumably secondary to the hypercoagulable state associate with inflammatory bowel disease), and nonsurgical management can be successful in the short term.
Acknowledgment: The authors thank Sheetal Shah and Kelly Limjoco for assistance in preparing this manuscript.
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