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Decreased tissue factor pathway inhibitor ( TFPI )‐dependent anticoagulant capacity in patients with cirrhosis who have decreased protein S but normal TFPI plasma levels
Author(s) -
Potze Wilma,
Arshad Freeha,
Adelmeijer Jelle,
Blokzijl Hans,
Berg Arie P.,
Meijers Joost C. M.,
Porte Robert J.,
Lisman Ton
Publication year - 2013
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/bjh.12462
Subject(s) - tissue factor pathway inhibitor , protein s , protein c , medicine , cirrhosis , endocrinology , thrombin , tissue factor , antibody , protein s deficiency , immunology , coagulation , platelet
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.