Decreased tissue factor pathway inhibitor (TFPI)‐dependent anticoagulant capacity in patients with cirrhosis who have decreased protein S but normal TFPI plasma levels. (11th July 2013)

• Record Type: Journal Article
• Authors: Potze, Wilma; Arshad, Freeha; Adelmeijer, Jelle; Blokzijl, Hans; van den Berg, Arie P.; Meijers, Joost C. M.; Porte, Robert J.; Lisman, Ton
• Is Part Of: British journal of haematology. Volume 162:Number 6(2013:Sep.)
• Page Start: 819
• Page End: 826
• Publication Date: 2013-07-11
• Subjects: cirrhosis -- coagulation -- tissue factor pathway inhibitor -- protein S -- thrombin generation; Hematology -- Periodicals; Blood -- Diseases -- Periodicals; 616.15
• DOI: 10.1111/bjh.12462
• Languages: English
• ISSNs: 0007-1048

Abstract

Summary: Protein S acts as a cofactor for tissue factor pathway inhibitor (TFPI) in the down regulation of thrombin generation, and acquired and congenital protein S deficiencies are associated with a concomitant TFPI deficiency. In contrast, in patients with liver diseases, decreased protein S, but normal or increased levels of TFPI have been reported. We compared TFPI and protein S plasma levels between 26 patients with cirrhosis and 20 healthy controls and found that TFPI levels were comparable between patients (111 ± 38%) and controls (108 ± 27%), despite reduced protein S levels (74 ± 23% in patients vs. 98 ± 10% in controls). Subsequently, we quantified the activity of the TFPI‐protein S system by measuring thrombin generation in the absence and presence of neutralizing antibodies to protein S or TFPI. Ratios of peak thrombin generation in the absence and presence of these antibodies were calculated. Both the protein S and the TFPI ratios were increased in patients with cirrhosis compared to controls. Protein S ratios were (0·62 [0·08–0·93] in patients vs. 0·32 [0·20–0·54] in controls; TFPI ratios were 0·50 [0·05–0·90] in patients vs. 0·18 [0·11–0·49] in controls). Thus, although the acquired protein S deficiency in patients with cirrhosis is not associated with decreased TFPI levels, the TFPI/protein S anticoagulant system is functionally impaired.