Hereditary thrombophilia as a cause of Budd-Chiari syndrome: A study from Western India

Abstract

The inherited deficiencies of protein C, protein S, antithrombin III, factor V Leiden mutation, prothrombin gene polymorphism, and antiphospholipids were studied in 53 Budd-Chiari syndrome (BCS) and 33 portal vein thrombosis (PVT) cases and compared with 223 age-and sex-matched controls. Protein C deficiency was detected in 7 (13.2%), protein S in 3 (5.7%), and antithrombin III in 2 (3.8%) of the BCS cases. Factor V Leiden was the most common risk factor, i.e., 14 of 53 (26.4%) in BCS cases followed by protein C, as compared with PVT cases, i.e., 2 of 33 (6.06%) and controls, i.e., 5 of 223 (2.3%). In PVT cases, protein C deficiency was present in 3 (9.09%), protein S deficiency in 1 (3.03%), and factor V Leiden mutation in 2 (6.06%) of the cases. The prothrombin gene polymorphism was not found in either the controls or the patients. The antiphospholipids were seen in 11 (20.75%) of the BCS cases and 6 (18.18%) of the PVT cases. Other acquired risk factors like pregnancy, surgery, and oral contraceptives were present in 8 (15.09%) of BCS and 3 (9.09%) of PVT cases. Thus overall, 59% of the BCS and 30% of the PVT cases could be explained by at least one of the etiologic factors studied. (HEPATOLOGY 2001;34: 666-670.)Budd-Chiari syndrome (BCS) is a rare disorder, the cause of which remains undetermined in the majority of cases. It is caused by the occlusion of hepatic outflow either at the level of hepatic veins or inferior vena cava. The disease, however, has been associated with a variety of conditions like malignancy, 1,2 polycythemia rubra vera, 3 paroxysmal nocturnal hemoglobinuria, 4 trauma, 5 pregnancy, 6 oral contraceptives, 7 and infection. 8 The clinical manifestations include hepatomegaly, portal hypertension, and liver function failure. Portal vein thrombosis (PVT) manifests itself as portal hypertension with decreased portal flow. Hypercoagulability has been implicated in both BCS and PVT.Except for a single report 9 published recently, there have not been many reports on the prevalence of the common factors for hypercoaguability, i.e., protein C, protein S, antithrombin III, factor V Leiden, and prothrombin gene polymorphism, studied in a large group of patients. There have only been isolated case reports in the literature describing BCS cases and the association of single prothrombotic factors 10-13 ; however, a systematic prospective study investigating all the prothrombotic factors simultaneously in BCS and PVT cases is lacking. MATERIALS AND METHODSPatients. The patients were referred from the Department of Gastroenterology, KEM Hospital, Mumbai, India, between 1995 and 2000. The diagnostic criteria for BCS was partial or complete obstruction of hepatic outflow or inferior vena cava, and for PVT, partial or complete obstruction of portal vein. The confirmation was done by Doppler sonography, magnetic resonance imaging, computed tomography scanning, and venography. The clinical details were recorded in a well-defined clinical proforma, which included details like number of thrombotic events, famil...

Changing spectrum of Budd-Chiari syndrome in India with special reference to non-surgical treatment

“…All previous Indian series, except two [29,32] , describe the predominance of IVC up to 79.2% [7,9,[11][12][13]15,30,39,40,42] or IVC-HV obstruction up to 57.7% [14,24,25,35] ; HV involvement was described in 0%-32% of cases in these series [7,9,[11][12][13][14][15]24,25,30,35,39,40,42] . Of the two distinct previous series, one (total 53 cases) showed similar frequency of HV (35.8%), IVC (33.9%) and combined IVC-HV involvement (30.1%) [29] ; whereas the other series involving only chronic BCS showed predominance of HV (45.9%) followed by combined IVC-HV (29.7%) and IVC involvement (24.3%) [32] . In the western countries, hepatic vein thrombosis remains responsible for majority of BCS cases, IVC obstruction is rarely found.…”

“…Previously, MOVC was thought to be the predominant cause of IVC involvement (20.4%-58.6%) and of BCS in India [6,7,[11][12][13][14][15]17,29,35,39] , as well as in Asian countries [49,50,53] . In two recent Indian studies, MOVC was present in 0% and 17.2%, while IVC involvement was seen in 56.2% and 62% cases, respectively [24,40] .…”

“…In our series, IVC involvement in the majority of cases was due to IVC thrombosis. Previously, MOVC and IVC thrombosis were considered to be idiopathic in origin by most Indian and Asian workers [5,6,11,[13][14][15]17,35,49,50,53,54] ; but this view has been challenged recently in a few reports [22,29,30,42,[55][56][57][58] . In cases of IVC thrombosis in our study, the etiology was identified in 50%.…”

“…Tumors, pregnancy, oral contraceptive pills (OCP) and infections were proposed as predominant underlying etiologies, hypercoagulable states were uncommon, and idiopathic cases were the most common [9,[12][13][14][15][16][17][18][19][20][21]42] . In the series of cases during the last 10 years, various hypercoagulable states are being increasingly described as etiologies of BCS [24][25][26][28][29][30]46,47] .…”

Portal Vein Thrombosis

“…Protein C deficiency is seen in 8-9%, protein S deficiency in 3-4%, factor V Leiden mutation in 3-6% and antiphospholipid antibody in 18-23%. 11,[33][34][35] Antithrombin III deficiency and prothrombin gene mutation are however uncommon. However another study from India of 26 PVT patients showed the presence of protein C deficiency in 12, protein S deficiency in 9, antithrombin III deficiency in 8 patients, ACLA in 3 and LA in 4 patients.…”