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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

Potze, W., Arshad, F., Adelmeijer, J., Blokzijl, H., van den Berg, A. P., Meijers, J. C. M., Porte, R. J. & Lisman, T., Sep-2013, In : British Journal of Haematology. 162, 6, p. 819-826 8 p.

Research output: Contribution to journalArticleAcademicpeer-review

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. 018 [011-049] 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.

Original languageEnglish
Pages (from-to)819-826
Number of pages8
JournalBritish Journal of Haematology
Volume162
Issue number6
Publication statusPublished - Sep-2013

    Keywords

  • cirrhosis, coagulation, tissue factor pathway inhibitor, protein S, thrombin generation, DISSEMINATED INTRAVASCULAR COAGULATION, VENOUS THROMBOEMBOLISM, THROMBIN GENERATION, LIVER-DISEASE, HEPATOCELLULAR DISEASE, HYPERCOAGULABILITY, CONSEQUENCES, HEMOSTASIS, DEFICIENCY, FAILURE

ID: 5943621