Vaginal bleeding in early pregnancy and circulating markers of thrombin generation

Abstract

Objective: To determine if subjects experiencing acute vaginal bleeding in early pregnancy have increased plasma markers of thrombin generation compared to nonbleeding controls. Methods: Subjects with clinically apparent acute (within 24 h of sample collection) vaginal bleeding between 6 and 20 weeks estimated gestational age and without known thrombophilias were enrolled, along with nonbleeding controls, and underwent collection of maternal plasma. Concentrations of thrombin-antithrombin (TAT) and fragment 1 + 2 (F1 + 2) were determined by enzyme-linked immunosorbent assay. Differences between bleeding and nonbleeding subjects were assessed through linear regression with adjustment for gestational age. Results: Twenty subjects with vaginal bleeding and 20 controls were included. Bleeding was significantly associated with increased concentrations of TAT (p = 0.007) and F1 + 2 (p = 0.044) when corrected for gestational age. Among bleeding subjects, there was no association between markers of thrombin generation and the subject’s description of bleeding quantity, though higher concentrations were associated with a longer self-reported duration of bleeding. Conclusions: Clinically apparent vaginal bleeding in early pregnancy is associated with increased circulating maternal markers of thrombin generation. Thus, these maternal markers may have a future role in risk stratification.

Keywords::

• Vaginal bleeding
• threatened abortion
• threatened miscarriage
• thrombin
• thrombin-antithrombin complexes
• fragment 1 and 2

Acknowledgments

The authors would like to acknowledge the role of Linda Salamone in laboratory assistance and Linda Leoni RN, Jessica Marino and Erin Lemke-Berno RDMS, MPH in subject enrollment and recruitment.

Declarations of interest: The authors report no declarations of interest. This research was funded by Women’s Reproductive Health Research K-12: HD001332-09.