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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.
MedLine Citation:
PMID:  23841464     Owner:  NLM     Status:  Publisher    
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.
Wilma Potze; Freeha Arshad; Jelle Adelmeijer; Hans Blokzijl; Arie P van den Berg; Joost C M Meijers; Robert J Porte; Ton Lisman
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2013-7-11
Journal Detail:
Title:  British journal of haematology     Volume:  -     ISSN:  1365-2141     ISO Abbreviation:  Br. J. Haematol.     Publication Date:  2013 Jul 
Date Detail:
Created Date:  2013-7-11     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0372544     Medline TA:  Br J Haematol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
© 2013 John Wiley & Sons Ltd.
Surgical Research Laboratory, University of Groningen, University Medical Centre Groningen, Groningen, The Netherlands.
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