Abstract

Background Budd-Chiari syndrome (BCS) and Portal Vein Thrombosis (PVT) have been associated with several hypercoagulable states. Thrombin-activatable fibrinolysis inhibitor (TAFI) potently attenuates fibrinolysis. Elevated TAFI antigen levels form a risk factor for deep venous thrombosis and are to a high extend genetically determined. To establish the pathogenetic role of TAFI in BCS and PVT, we studied TAFI antigen levels and gene polymorphisms in patients with BCS, PVT and matched controls.

Methods In a multicenter case-control study, 39 patients with BCS, 85 patients with PVT and 118 population-based controls were identified. Plasma levels of TAFI antigen were determined by a commercially available ELISA and polymorphisms of the TAFI gene (TAFI 505A/G and TAFI 1040C/T) were analysed by PCR. Because TAFI antigen levels are decreased in patients with impaired liver synthesis, plasma levels were corrected for antithrombin activity levels. ANOVA techniques were used to correlate TAFI polymorphisms with TAFI antigen levels.

Results Mean plasma TAFI antigen levels were significantly lower in BCS and/or PVT patients as compared to controls, even after adjusting for impaired liver function by antithrombin activity levels (all p<0.002). There was a strong correlation between the TAFI 505 A/G and TAFI 1040 C/T polymorphisms and plasma TAFI antigen levels in all groups (all p<0.001). The G-allele of the 505A/G polymorphism was associated with a low antigen level of TAFI. Carriers of the GG genotype had an increased risk for BCS and/or PVT (OR=4.4; 95% CI 1.5–12.6). Carriers of the G allele showed a risk of 4.1 (95% CI 1.5–11.5). For the 1040C/T polymorphism, the T allele was associated with lower levels of TAFI antigen, and carriers of at least one copy of the T allele showed an OR of 1.6 (95% CI 0.9–2.7).

Conclusion We found lower TAFI levels in patients with BCS and/or PVT than in healthy controls. In addition two TAFI genotypes, associated with lower TAFI antigen levels were found more frequently in patients with BCS and/or PVT than in healthy controls. Therefore low TAFI levels appear to be a risk factor for the development of BCS and PVT. These results suggest a different pathogenetic mechanism of TAFI in BCS and PVT than in deep venous thrombosis.

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