scholarly journals Tissue Factor Pathway Inhibitor, Activated Protein C Resistance, and Risk of Ischemic Stroke due to Postmenopausal Hormone Therapy

Stroke ◽  
2012 ◽  
Vol 43 (4) ◽  
pp. 952-957 ◽  
Author(s):  
Jacques E. Rossouw ◽  
Karen C. Johnson ◽  
Mary Pettinger ◽  
Mary Cushman ◽  
Per Morten Sandset ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
Hormone Therapy ◽  
Tissue Factor ◽  
Protein C ◽  
Tissue Factor Pathway Inhibitor ◽  
Activated Protein C ◽  
Postmenopausal Hormone Therapy ◽  
Activated Protein C Resistance ◽  
Postmenopausal Hormone ◽  
Tissue Factor Pathway

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

2011 ◽  
Vol 106 (11) ◽  
pp. 914-921 ◽  
Author(s):  
M. Christella Thomassen ◽  
Serban-Dan Costa ◽  
Louis Peeters ◽  
Jan Rosing ◽  
Svetlana Tchaikovski
Keyword(s):  
Tissue Factor ◽  
Protein C ◽  
Thrombin Generation ◽  
Tissue Factor Pathway Inhibitor ◽  
Activated Protein C ◽  
Protein S ◽  
Apc Resistance ◽  
Thrombosis Risk ◽  
History Of ◽  
Tissue Factor Pathway

SummaryPregnancy 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.

The anticoagulant action of recombinant human activated protein C (rhAPC, Drotrecogin α activated): comparison between cord and adult plasma

2004 ◽  
Vol 91 (05) ◽  
pp. 912-918 ◽  
Author(s):  
Siegfried Gallistl ◽  
Martin Koestenberger ◽  
Katrin Baier ◽  
Peter Fritsch ◽  
Joachim Greilberger ◽  
...  
Keyword(s):  
Tissue Factor ◽  
Protein C ◽  
Tissue Factor Pathway Inhibitor ◽  
Activated Protein C ◽  
Clotting Time ◽  
Promising Candidate ◽  
Anticoagulant Action ◽  
Adult Plasma ◽  
Tissue Factor Pathway

SummaryThe present study was performed to compare the anticoagulant efficiency of recombinant human activated protein C (rhAPC) in cord with that in adult plasma. RhAPC is a promising candidate to improve the outcome of severe sepsis. However, different anticoagulant efficiency of rhAPC in cord compared with adult plasma has to be expected due to physiological low plasma levels of tissue factor pathway inhibitor (TFPI) and antithrombin (AT) present in neonates, two inhibitors known to markedly influence the anticoagulant action of APC. Clot formation was induced in our experiments by addition of high (30 µM) or low (20 pM) amounts of lipidated tissue factor (TF). High amounts of TF are conventionally applied in standard clotting assays, whereas plasma activation with low amounts of TF probably better matches the conditions in vivo. We demonstrate that under low coagulant challenge increasing amounts of rhAPC (0.1 – 0.5 µg/ml final plasma concentration) dose-dependently prolonged clotting time and suppressed thrombin potential and prothrombin fragment 1 + 2 generation in both cord and adult plasma. The same was true for experiments performed under high coagulant challenge when 4 – 16 µg/ml of rhAPC were added. Whereby, cord plasma was significantly more susceptible to addition of rhAPC in the presence of high amounts of TF and adult plasma was significantly more susceptible to addition of rhAPC in the presence of low amounts of TF. We demonstrate that increased anticoagulant efficiency of rhAPC in adult plasma under low coagulant challenge is attributable to the physiological high levels of TFPI and AT present in adults.

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