P497 Direct Sequencing of Protein-C and -S Genes in Patients with Budd–Chiari Syndrome (BCS), Portal-Vein Thrombosis (PVT) and Obliterative-Portal-Venopathy (Opv) and Suspicion of Inherited Protein-C or -S Deficiency (original) (raw)

Journal of Hepatology, 2014

Abstract

P497 DIRECT SEQUENCING OF PROTEIN-C AND -S GENES IN PATIENTS WITH BUDD–CHIARI SYNDROME (BCS), PORTAL-VEIN THROMBOSIS (PVT) AND OBLITERATIVEPORTAL-VENOPATHY (OPV) AND SUSPICION OF INHERITED PROTEIN-C OR -S DEFICIENCY A. Plessier, L. Elkrief, P.E. Rautou, E. Deraucourt, O. Goria, K. Zekrini, L. Boudaoud, D. Valla, M. Alhenc Gelas. Department of Hepatology, Hopital Beaujon, AP-HP, University Paris-Diderot, INSERM U 773, Department of Hematology, Haemostasis and Biology, AP-HP, Hopital Beaujon, INSERM U 773 & Universite Paris-VII, Clichy, Department of Gastroenterology, Hepatology, CHU Rouen, Rouen, Hopital Beaujon, AP-HP, University Paris-Diderot, INSERM U 773, Service d’Hepatologie, Clichy, Department of Hematology, Haemostasis and Biology, AP-HP, Hopital Europeen Georges Pompidou, INSERM & Universite Paris, Paris, France E-mail: aurelie.plessier@bjn.aphp.fr Background and Aims: Protein C (PC) and S (PS) deficiencies identified in up to 30% of vascular liver disease patients, are possible risk factors for such diseases, but may alternatively be a mere consequence of liver dysfunction. To address this point, we analyzed PROC or PROS1 genes in these patients with PC or PS deficiency suspicion. Methods: Out of 150 PVT, 74 BCS, 30 OPV, currently included in the dedicated database for vascular disease, inherited PC or PS deficiency [isolated deficiency (protein C clotting activity <70% or PS activity <60% in men, <55% in women), or low level compared to other vitamin K dependent factors level] was suspected in 26 patients (10 BCS, 11 PVT, and 5 OPV) in whom direct sequencing of PROC (N =13) or PROS1 (N =14) genes was performed. Results: Mean (±SD) PC or PS activity was 50±10% and 43±8% respectively. Detrimental PROC or PROS1 heterozygous mutations were found in 38% (N=5) and 29% (N=4) patients, respectively (7 PVT and 2 OPV). No significant differences in PC or PS activity levels were observed between detrimental mutation carriers and non-carriers. Other risk factors for thrombosis (myeloproliferative disease, antiphospholipid syndrome) were present in 4 of 9 heterozygotes. Mutation carrying was associated with initial thrombosis of other splanchnic veins (100%vs18%, p < 0.001). Conclusions: Detrimental mutations of PROC and PROS1 were identified in a proportion of patients with PVT or OPV, but not BCS. Isolated low PC or PS levels in BCS patients appear to result mostly from altered liver function.

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