Inherited Prothrombotic Defects in Budd-Chiari Syndrome and Portal Vein Thrombosis : A Study From North India

Abstract

We studied 57 patients with Budd-Chiari syndrome (BCS) and 48 with portal vein thrombosis (PVT) for underlying inherited prothrombotic defects such as protein C, protein S, and antithrombin III deficiencies. Genetic mutations for factor V Leiden, prothrombin gene 20210A, and methyltetrahydrofolate reductase (MTHFR) C677T were studied in 29 patients in each group. Inherited prothrombotic defects were detected in 16 (28%) of 57 patients with BCS and 7 (15%) of 48 patients with PVT. Factor V Leiden mutation was the most common prothrombotic defect in BCS (5/29 [17%]) followed by protein C deficiency (7/57 [12%]) and protein S deficiency (4/57 [7%]), whereas in PVT, protein C deficiency was the most common inherited prothrombotic defect (4/48 [8%]) followed by protein S deficiency (2/48 [4%]). The factor V Leiden mutation was detected in only 1 (3%) of 29 cases of PVT. The heterozygous MTHFR C677T mutation was detected in 7 (24%) of 29 patients with BCS and 6 (21%) of 29 patients with PVT. Antithrombin III deficiency, homozygous MTHFR C677T mutation, and prothrombin G20210A mutation were not detected in any patients.

PAI-1 4G-4G, MTHFR 677TT, V Leiden 506Q, and Prothrombin 20210A in Splanchnic Vein Thrombosis: Analysis of Individual Patient Data From Three Prospective Studies

“…We think that PAI-1 4G-4G and MTHFR 677TT can increase the inflammation response, participating to the activation of perisinusoidal hepatic stellate cells, causing hepatic fibrosis and augmented intrahepatic vascular resistance typical of the LC, as suggested by Fernandez. 13 V Leiden 506Q was significantly correlated with BCS patients (13/45 patients), confirming other previous articles on BCS, 14,15 but Hardy-Weinberg equilibrium for V Leiden 506Q was respected both in patients with SVT and in HC.…”

Portal Vein Thrombosis

“…37 Heterozygous MTHFR has been reported in 21% of PVT patients and hyperhomocysteinemia in 7.6% while homozygous MTHFR has not been seen. 11 A strong link of Bacteroides fragillus infection with PVT has also been demonstrated possibly due to transient development of anti-cardiolipin antibodies. 38 Other conditions that are associated with PVT are use of oral contraceptives, cytomegalovirus infection, 39 pregnancy, chronic inflammatory diseases and malignancies in the background of the above prothrombotic causes.…”

“…In upto 80% cases the underlying cause is identified when rigorously searched for. [8][9][10][11][12][13] In some cases multiple prothrombotic factors may be associated in the development of PVT. [14][15][16] In one study one or more risk factors namely prothrombotic state or abdominal inflammation was present in 87% of patients.…”

“…27 Other prothrombotic conditions that cause PVT include paroxysmal nocturnal hemoglobinuria (PNH), antiphospholipid syndrome, hyperhomocysteinemia, inherited prothrombotic disorders such as protein C (in 0-9.1%), S (0.9-30%) and antithrombin III deficiencies (0-4.5%) and less frequently factor V Leiden mutation (1.3-7.6%), factor II mutation (G20210A in 0-22%) and methylenetetrahydrofolate reductase (MTHFR) gene mutation. [9][10][11] These inherited disorders may be a secondary phenomenon rather than primary, since they are produced from the liver and may be affected in parenchymal liver disease. They may ultimately be confirmed by investigating first degree relatives.…”

“…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.…”