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Thromb Haemost 2003; 90(06): 1074-1079
DOI: 10.1160/TH03-02-0119
Blood Coagulation, Fibrinolysis and Cellular Haemostasis
Schattauer GmbH

Circulating levels of inflammatory cytokines (IL-1β and TNF-α), resistance to activated protein C, thrombin and fibrin generation in uncomplicated pregnancies

De-Hui W. Ku
1   The Center for Thrombosis in Women Health, Obstetrics and Gynecology Department, Yale University, New Haven, Connecticut, USA
,
Yale S. Arkel
1   The Center for Thrombosis in Women Health, Obstetrics and Gynecology Department, Yale University, New Haven, Connecticut, USA
,
Michael P. Paidas
1   The Center for Thrombosis in Women Health, Obstetrics and Gynecology Department, Yale University, New Haven, Connecticut, USA
,
Charles J. Lockwood
1   The Center for Thrombosis in Women Health, Obstetrics and Gynecology Department, Yale University, New Haven, Connecticut, USA
› Author AffiliationsFinancial support: Study performed in part at Maine Medical Research Institute, Scarborough, ME. CJL supported by NIHR01 HD33937 grant.
Further Information

Publication History

Received 25 February 2001

Accepted after resubmission 09 September 2003

Publication Date:
05 December 2017 (online)

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Summary

We studied 33 women during normal uneventful pregnancies and with no history of previous adverse pregnancy events for markers of activated coagulation and thrombin activity including prothrombin fragment 1.2(PF1.2), thrombin- antithrombin (TAT), and soluble fibrin polymer (SFP). In addition, we measured potential thrombin generation through the addition of thromboplastin to patient plasma in the presence of a throm-bin-specific chromogenic substrate determined serially over a period of time - Endogenous Thrombin Potential assay (ETP). This assay was performed with plasma treated and untreated with activated protein C (APC). The fibrinolytic system was assessed by measurement of thrombin activatable fibrinolysis inhibitor (TAFI). These findings were correlated with the levels of pro-inflammatory cytokines, interleukine-1β and tumor necrosis factor-α. Our data supports previous reports that indicate that resistance to activated protein C and coagulation activation markers are commonly increased in the later 2/3rds of pregnancy. There are no differences in thrombin generation potential, as determined by the ETP assay without the addition of APC, in the three trimesters. However, the thrombin reserve (TR), the ETP result without APC divided by the ETP result with the addition of APC, is increased above the reference range in the 2nd and 3rd trimesters. Patients with increased TR and resistance to APC had increased levels of TNF-α. Increased proinflammatory cytokines are reportedly associated with changes in the APC system with a decrease in the ability to generate APC. A sub-group of pregnancies with APC resistance had increased levels of TNF-α and may be important in the risk for adverse pregnancy outcomes.

Keywords

ETP - activation markers - pro-inflammatory cytokines - TAFI
 

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