Tissue factor-dependent thrombin generation across pregnancy

Abstract

Objective: Normal pregnancy results in a prothrombotic state. Studies that have investigated the capacity of pregnant women to generate thrombin are limited. Our aim was to evaluate thrombin generation longitudinally from the preconception period, through pregnancy, and after pregnancy.

Study design: We evaluated young, healthy nulligravid women (n = 20) at 4 time points and compared the data with 10 control women at 2 time points. Coagulation was initiated with tissue factor in contact pathway inhibited plasma, and thrombin generation was determined in the presence of a fluorogenic substrate.

Results: The maximum level and rate of thrombin generation increased during pregnancy; the highest level and rate occurred in late pregnancy compared with prepregnancy (P < .001). Subsequently, thrombin generation decreased in the postpregnancy samples that included maximum level, rate, and area under the curve (P < .001).

Conclusion: Our data provide evidence for an increase in tissue factor-dependent thrombin generation with pregnancy progression, followed by a return to prepregnancy thrombin levels.

Figure 1. Thrombin Generation Parameters

Box plot shows thrombin parameters for 20 pregnant women over 4 time points and 10 control subjects at 2 time points (C1, C2): A, max level; B, peak rate; C, area under the curve (AUC). The boundary of each box closest to zero indicates the 25th percentile, the boundary furthest from zero indicates the 75th percentile. The line within each box represents the median. Error bars represent the 90th and 10th percentiles; samples outside of these parameters are represented as outlying points (closed circles). NS, not statistically significant; Pre, prepregnancy; Post, after pregnancy; RFU/s, relative fluorescence units.

Figure 2. Longitudinal Thrombogram

Thrombograms for 1 individual: A) before conception, B) in early pregnancy, C) in late pregnancy, D) 1 year after delivery. In all panels, closed circles represent reactions initiated with 5pmol/L Tf in the presence of Ca+2 and 20-µmol/L phospholipid vesicles. Tf, tissue factor.