Deficiency of natural anticoagulant proteins C, S, and antithrombin in portal vein thrombosis: a secondary phenomenon?

Background-Hereditary deficiencies of natural anticoagulant proteins are im plicated in the pathogenesis of portal vein thrombosis (PVT). Secondary def iciencies of these proteins have also been reported in PVT, making interpre tation of concentrations difficult. Aims-To characterise the coagulation profiles in adult patients with PVT an d to investigate the possible mechanisms of natural anticoagulant protein d eficiency. Patients-Twenty nine adult patients with portal hypertension caused by PVT, and normal biochemical liver function tests. Methods-Routine coagulation profiles and concentrations of proteins C, S, a nd antithrombin were measured; where indicated, corresponding concentration s in parents were also measured. Synchronous peripheral and hepatic or sple nic vein concentrations were compared in seven patients undergoing interven tional procedures, as were peripheral concentrations before and after shunt surgery in three patients. Results-Deficiencies of one or more of the natural anticoagulant proteins o ccurred in 18 patients (62%), with six patients having combined deficiency of all three proteins. There were strong correlations between prothrombin a nd partial thromboplastin time ratios and: concentrations of natural antico agulant proteins. Family studies in nine cases of anticoagulant protein def iciency revealed possible hereditary deficiency in only three cases, and si gnificantly lower concentrations of anticoagulant proteins in all PVT cases compared with parents. Levels of anticoagulant proteins tended to be lower in hepatic veins but higher in splenic veins compared with peripheral vein concentrations. Peripheral concentrations decreased after shunt surgery. Conclusions-Deficiency of natural anticoagulant proteins is common in PVT a nd is probably a secondary phenomenon in most cases, occurring as part of a global disturbance of coagulation variables. The mechanism for this remain s unclear but may result from a combination of reduced hepatic blood flow a nd portosystemic shunting itself.