Portal Vein Thrombosis Due to Hyperhomocysteinemia Caused by Vitamin B-12 Deficiency

C 2005) Digestive Diseases and Sciences, Vol. 50, No. 12 (December 2005), pp. 2362–2363 (
DOI: 10.1007/s10620-005-3064-0

Portal Vein Thrombosis Due to Hyperhomocysteinemia Caused by Vitamin B-12 Deficiency MEHMET KANBAY, MD, SEMA KARAKUS, MD, and UGUR YILMAZ, Prof KEY WORDS: acute abdominal pain; portal vein thrombosis; homocysteine; vitamin B-12.

Thrombosis of the portal vein is rare, but this condition can lead to serious complications (1, 2). Portal vein thrombosis (PVT) can occur due to infection, protein C or protein S deficiency, trauma, drugs, or mutations of the gene for methylenetetrahydrofolate and prothrombin gene G20210A (1–3). The imaging modalities used to diagnose this condition include ultrasonography and computed tomography (CT). Here we describe what, to our knowledge, is the first reported case of PVT secondary to hyperhomocysteinemia caused by vitamin B-12 deficiency. CASE REPORT A 36-year-old male presented to our hospital complaining of nausea and abdominal pain that had lasted for 4 days. The patient was not a smoker, his medical history was unremarkable, and he was on no medications. His vital signs on admission were as follows: temperature, 36.7◦ C; blood pressure, 120/70 mm Hg; and heart rate, 84 beats/min. His oxygen saturation level was 96%. No abnormalities were detected on cardiopulmonary or urologic examination. Abdominal palpation revealed tenderness in the right upper quadrant, with guarding and peritoneal signs. Laboratory data on admission showed aspartate aminotransferase of 152 U/L (normal, 0–40), alanine aminotransferase of 174 U/L (0–41), alkaline phosphatase of 480 U/L (15–250), γ -glutamyltransferase of 110 U/L (8–61), total bilirubin of 1.9 mg/dl (0.2–1.2), direct bilirubin of 4.26 mg/dl (0–0.25), C-reactive protein of 64 mg/L (0– 10), hemoglobin of 7.4 g/dl (12–16), white blood cell count of 2490 K/mm3 , platelet count of 67,800 K/mm3 , mean corpuscular volume of 121 fl (80–96), vitamin B-12 of 124 pg/ml

Manuscript received January 16, 2004; accepted January 25, 2005. From the Deparment of Internal Medicine, Baskent University Faculty of Medicine, Ankara, Turkey. Address for reprint requests: Dr. Mehmet Kanbay, Department of Internal Medicine, Baskent University Faculty of Medicine, 35 Sokak 81/5 Emek, Ankara 06490, Turkey.

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(157–1059), folic acid of 10.5 ng/ml (3–17), lactate dehydrogenase of 2570 U/L (200–450), and homocysteine of 46.8 µg/L (4.5–15). Serum creatinine was normal and there were no abnormal findings on urinalysis. Chest and abdominal x-rays and an electrocardiogram were obtained, and these showed nothing remarkable. Abdominal ultrasonography (Philips HDI 5000) revealed a tubular hypoechoic lesion in the portal vein. Further investigation with Doppler ultrasonography revealed no blood flow at the lesion site. The liver appeared normal. The patient was diagnosed with PVT and was placed on anticoagulant therapy with unfractionated heparin and warfarin. Once this treatment was started, his condition improved dramatically. However, follow-up ultrasonography 40 days after admission showed that the thrombus persisted. At this stage, the patient was tested for coagulation disorder using blood that had been collected before anticoagulant therapy was started. The results for protein C deficiency, protein S deficiency, lupus anticoagulant, factor V Leiden mutation, antinuclear antigen, anti-double-stranded DNA, antithrombin III, and viral markers were all negative. Laboratory testing did reveal megaloblastic anemia and hyperhomocysteinemia due to vitamin B-12 deficiency, so the patient was started on vitamin B-12 supplementation. Three months after initiation of vitamin B-12 therapy, the patient’s complete blood cell count, lactate dehydrogenase level, and homocysteine level were normal.

DISCUSSION The patient presented here had no risk factors for PVT other than hyperhomocysteinemia caused by vitamin B12 deficiency. The literature contains two other cases of PVT associated with hyperhomocysteinemia (1, 2), but, to our knowledge, our is the first report of PVT due to hyperhomocysteinemia caused by vitamin B-12 deficiency. Research has shown that hyperhomocysteinemia is a risk factor for thromboembolic events and for cardiovascular disease (3, 4). The pathophysiological mechanisms that underlie homocysteine-induced vascular disease are Digestive Diseases and Sciences, Vol. 50, No. 12 (December 2005)

C 2005 Springer Science+Business Media, Inc. 0163-2116/05/1200-2362/0


PORTAL VEIN THROMBOSIS DUE TO HYPERHOMOCYSTEINEMIA

not well understood. It is even unclear whether homocysteine itself is primarily responsible for the thrombogenic effects of hyperhomocysteinemia in vivo or whether these effects are caused by a related metabolite or cofactor. In conclusion, this case provides more evidence that hyperhomocysteinemia can cause PVT and highlights that this condition should be included in the differential diagnosis for PVT. We emphasize the importance of measuring serum homocysteine in all patients with PVT to avoid missing this rare but probably curable condition.

Digestive Diseases and Sciences, Vol. 50, No. 12 (December 2005)

REFERENCES 1. Audemar F, Denis B, Blaison G, Mazurier I, Peter A, Serbout R: Left branch portal vein thrombosis associated with hyperhomocysteinemia. Gastroenterol Clin Biol 23(12):1388–1391, 1999 2. Spanier BWM, Frederiks J: Aetiology of extrahepatic portal vein thrombosis. Gut 51:755–756, 2002 3. Denninger MH, Chait Y, Casadevall N, et al.: Cause of portal or hepatic venous thrombosis in adults: the role of multiple concurrent factors. Hepatology 31:587–591, 2000 4. Deloughery TG, Evans A, Sadeghi A, et al.: Common mutation in methylenetetrahydrofolate reductase.Correlation with homocysteine metabolism and late-onset vascular disease. Circulation 94:3074– 3078, 1996

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