RGD Reference Report - Decreased tissue factor pathway inhibitor (TFPI)-dependent anticoagulant capacity in patients with cirrhosis who have decreased protein S but normal TFPI plasma levels.

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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.
Authors:	Potze, W Arshad, F Adelmeijer, J Blokzijl, H Van den Berg, AP Meijers, JC Porte, RJ Lisman, T
Citation:	Potze W, etal., Br J Haematol. 2013 Sep;162(6):819-26. doi: 10.1111/bjh.12462. Epub 2013 Jul 11.
RGD ID:	11060135
Pubmed:	PMID:23841464 (View Abstract at PubMed)
DOI:	DOI:10.1111/bjh.12462 (Journal Full-text)
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.

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Object Symbol	Species	Term	Qualifier	Evidence	With	Notes	Source	Original Reference(s)
TFPI	Human	liver cirrhosis		IDA			RGD
Tfpi	Rat	liver cirrhosis		ISO	TFPI (Homo sapiens)		RGD
Tfpi	Mouse	liver cirrhosis		ISO	TFPI (Homo sapiens)		RGD

Objects Annotated

Genes (Rattus norvegicus)

Tfpi (tissue factor pathway inhibitor)

Genes (Mus musculus)

Tfpi (tissue factor pathway inhibitor)

Genes (Homo sapiens)

TFPI (tissue factor pathway inhibitor)

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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.