Portal Vein Thrombosis after Variceal Endoscopic Sclerotherapy in Cirrhotic Patients: Role of Genetic Thrombophilia

Background and Study Aims: Portal vein thrombosis is a rare event in patients with liver cirrhosis in the absence of a related neoplasm. Endoscopic sclerotherapy of esophageal varices has been anecdotally associated with the development of portal vein thrombosis. We tested the hypothesis that genetic thrombophilia plays a role in the development of portal vein thrombosis in patients with liver cirrhosis undergoing endoscopic sclerotherapy.
Patients and Methods: From June 1998 to December 1999, 61 consecutive patients underwent multiple sessions of endoscopic sclerotherapy for bleeding esophageal varices. Doppler ultrasound of the portal vein was performed before sclerotherapy and every 3 months thereafter. Antiphospholipid antibodies, factor V Leiden (FVL) mutation, prothrombin mutation G20210A (PTHRA20210) and mutation TT677 of methylenetetrahydrofolate reductase (MTHFR C677T) were evaluated in all patients.
Results: Portal vein thrombosis developed in 16 % of the patients (10 of 61) after a mean follow-up period of 16 months. A genetic cause for thrombosis was found in 70 % of patients with liver cirrhosis who developed portal vein occlusion, but only in 8 % of patients without this complication.
Conclusions: Endoscopic sclerotherapy of esophageal varices may represent a trigger factor for portal vein thrombosis in cirrhotic patients with genetic thrombophilia.

References

• 1 Okuda K, Ohnishi K, Kimura K. et al . Incidence of portal thrombosis in liver cirrhosis: an angiographic study in 708 patients.  Gastroenterology. 1985;  89 279-286
• 2 Orozco H, Takahashi T, Mercado M A. et al . Postoperative portal vein obstruction in patients with idiopathic portal hypertension.  J Clin Gastroenterol. 1990;  12 607
• 3 Gayowski T J, Marino I R, Doyle H R. et al . A high incidence of native portal vein thrombosis in veterans undergoing liver transplantation.  J Surg Res. 1996;  60 333-338
• 4 Amitrano L, Brancaccio V, Guardascione M A. et al . Inherited coagulation disorders in cirrhotic patients with portal vein thrombosis.  Hepatology. 2000;  31 345-348
• 5 Denninger M H, Chait Y, Casadevall N. et al . Cause of portal or hepatic venous thrombosis in adults: the role of multiple concurrent factors.  Hepatology. 2000;  31 587-591
• 6 Bengmark S, Borjesson B, Hoevels J. et al . Obliteration of esophageal varices by PTP: a follow-up of 34 patients.  Ann Surg. 1979;  190 549-554
• 7 Snady H. Acute portal vein thrombosis, sclerotherapy, and vasopressin: relationships and implications.  Am J Gastroenterol. 1987;  82 1292
• 8 Bengmark S, Borjesson B, Hoevels J. et al . Endoscopic sclerotherapy: a risk factor for splanchnic venous thrombosis.  J Vasc Surg. 1989;  10 9-12
• 9 Ashida H, Kotoura Y, Nishioka A. et al . Portal and mesenteric venous thrombosis as a complication of endoscopic sclerotherapy.  Am J Gastroenterol. 1989;  84 30
• 10 Terada T, Nakanuma Y. Portal, mesenteric, and splenic venous thrombosis after endoscopic injection sclerotherapy.  J Clin Gastroenterol. 1990;  12 238-239
• 11 Korula J, Yellin A, Kanel G C. et al . Portal vein thrombosis complicating endoscopic variceal sclerotherapy: Convincing further evidence.  Dig Dis Sci. 1991;  36 1164-1167
• 12 Qureshi H, Siddiqui K, Ahmad R. et al . Portal vein thrombosis following sclerotherapy.  Hepatogastroenterology. 1992;  39 427-428
• 13 Kawasaki S, Henderson J M, Riepe S P. et al . Endoscopic variceal sclerosis does not increase the risk of portal venous thrombosis.  Gastroenterology. 1992;  102 206-215
• 14 Margaglione M, di Minno G, Grandone E. et al . Raised plasma fibrinogen concentrations in subjects attending a metabolic ward: relation to family history and vascular risk factors.  Thromb Haemost. 1995;  73 579-583
• 15 Koeleman B PC, Reitsma P H, Allaart C F. et al . Activated protein C resistance has an additional risk factor for thrombosis in protein C-deficient families.  Blood. 1994;  84 1031-1035
• 16 Margaglione M, D'Andrea G, Cappucci G. et al . Detection of factor V Leiden mutation using SSCP.  Thromb Haemost. 1996;  76 814-815
• 17 Bertina M. Factor V Leiden and other coagulation factor mutation affecting thrombotic risk.  Clin Chem. 1997;  43 1678-1683
• 18 de Franchis R, Mancini F P, D'Angelo A. et al . Elevated total plasma homocysteine and C → T mutation of 5,10 methylenetetrahydrofolate reductase gene in thrombotic vascular disease.  Am J Hum Genet. 1996;  59 262-264
• 19 Grandone E, Margaglione M, Colaizzo D. et al . Factor V Leiden, C→T MTHFR polymorphism and genetic susceptibility to preeclampsia.  Thromb Haemost. 1997;  77 1052-1054
• 20 Ueno N, Sasaki A, Tomiyama T. et al . Color Doppler ultrasonography in the diagnosis of cavernous transformation of portal vein.  J Clin Ultrasound. 1997;  25 221-233
• 21 Mathieu D, Vasile N, Grenier P. Portal thrombosis: dynamic CT features and course.  Radiology. 1985;  154 737-741
• 22 Rosendaal F R. Venous thrombosis: a multicausal disease.  Lancet. 1999;  353 1167-1172
• 23 Phillips M D. Interrelated risk factors for venous thromboembolism.  Circulation. 1997;  95 1749-1751
• 24 Zoller B, Garcia de Frutos P, Hillarp A. et al . Thrombophilia as a multigenic disease.  Haematologica. 1999;  84 59-70
• 25 Politoske D, Ralls P, Korula J. Portal vein thrombosis following endoscopic variceal sclerotherapy.  Dig Dis Sci. 1996;  41 185-190
• 26 Mangia A, Margaglione M, Cascavilla I. et al . Anticardiolipin antibodies in patients with liver disease.  Am J Gastroenterol. 1999;  94 2983-2987
• 27 Bertina M. Factor V Leiden and other coagulation factor mutation affecting thrombotic risk.  Clin Chem. 1997;  43 1678-1683
• 28 Cattaneo M, Chantatangkul V, Taioli E. et al . The G20210 A mutation of the prothrombin gene in patients with previous first episodes of deep vein thrombosis: prevalence and association with factor V G1691A, methylenetetrahydrofolate reductase C677T and plasma prothrombin levels.  Thromb Res. 1999;  93 1-8
• 29 Janssen H LA, Meinardi J R, Vleggaar F P. et al . Factor V Leiden mutation, prothrombin gene mutation, and deficiencies in coagulation inhibitors associated with Budd-Chiari syndrome and portal vein thrombosis: results of a case-control study.  Blood. 2000;  96 2364-2368
• 30 Brown K, Luddington R, Baglin T. Effect of the MTHFR677T variant on risk of venous thromboembolism: interaction with factor V Leiden and prothrombin (F2G20210A) mutations.  Br J Haematol. 1998;  103 42-44
• 31 Poort S R, Rosendaal F R, Reitsma P H. et al . A common genetic variation in the 3′-untranslated region of the prothrombin gene is associated with elevated plasma prothrombin levels and an increase in venous thrombosis.  Blood. 1996;  15 3698-3703
• 32 Rosendaal F R, Doggen C J, Zivelin A. et al . Geographic distribution of the 20 210 G to A prothrombin variant.  Thromb Haemost. 1998;  79 706-708