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Thromb Haemost 2011; 106(05): 914-921
DOI: 10.1160/TH11-04-0244
Blood Coagulation, Fibrinolysis and Cellular Haemostasis
Schattauer GmbH

Role of protein S and tissue factor pathway inhibitor in the development of activated protein C resistance early in pregnancy in women with a history of preeclampsia

Svetlana N. Tchaikovski
1   Department of Biochemistry, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, The Netherlands
3   University Women's Hospital, Otto-von-Guericke University, Magdeburg, Germany
,
M. Christella L. G. D. Thomassen
1   Department of Biochemistry, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, The Netherlands
,
Serban-Dan Costa
3   University Women's Hospital, Otto-von-Guericke University, Magdeburg, Germany
,
Louis L. H. Peeters
2   Department of Gynaecology, University Hospital Maastricht, Maastricht, The Netherlands
,
Jan Rosing
1   Department of Biochemistry, Cardiovascular Research Institute Maastricht (CARIM), Maastricht University, Maastricht, The Netherlands
› Author Affiliations
Further Information

Publication History

Received: 17 April 2011

Accepted after major revision: 09 August 2011

Publication Date:
23 November 2017 (online)

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Summary

Pregnancy increases the risk of venous thromboembolism. Particularly in early pregnancy, the thrombosis risk can be attributed to the changes in coagulation. Elevated thrombin generation and resistance to activated protein C (APC) are likely to contribute to the increased thrombosis risk during pregnancy. We studied changes and the determinants of thrombin generation and APC resistance in the first 16 weeks of gestation in women with history of preeclampsia. Additionally, we investigated the influence of pregnancy-induced haemodilution on the coagulation system. We measured thrombin generation, APC resistance and plasma levels of prothrombin, factor V, factor X, protein S and tissue factor pathway inhibitor (TFPI) in 30 non-pregnant and 21 pregnant women at 8, 12 and 16 weeks of gestation. All participants shared a history of a hypertensive complication in the preceding pregnancy. Thrombin generation and APC resistance were higher at eight weeks of pregnancy than in the non-pregnant state, and progressively increased between eight and 16 weeks of gestation. Changes in the TFPI and protein S levels accounted for ~70% of pregnancy-induced APC resistance. Interestingly, a significant correlation (slope 2.23; 95%CI: 1.56 to 2.91; r= 0.58) was observed between protein Stotal or protein Sfree levels and haematocrit. In conclusion, pregnancy induces a decrease of TFPIfree and protein Sfree levels that attenuates the function of the TFPI and protein C systems and results in elevated thrombin generation and increased APC resistance. Besides, our data suggest that pregnancy-dependent haemodilution may contribute to the decreased peripheral protein S levels.

Keywords

Pregnancy - thrombin generation - APC resistance - protein S - TFPI - haematocrit
 

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