The effects of physiological concentrations of 17ß-Estradiol and Progesterone on fibrin network ultrastructure

Abstract

17β-Estradiol (E2) and progesterone (P4) have various important functions but the effect of these endogenous hormone concentrations on fibrin network formation has not been established. It is essential to understand natural hormone mechanisms since these hormones are still present in circulation while hormonal contraceptives, which are associated with increased risk of venous thromboembolism, are used. In this study the formation of a fibrin network is analysed when different physiological concentrations of E2 and P4 is added to platelet poor plasma. Blood coagulation is critical for haemostasis but when the formation of a stable clot is influenced in such a way that hypercoagulation takes its course, it can have detrimental effects as it increases the risk of venous thrombosis. During blood coagulation fibrinogen is converted into fibrin in the presence of thrombin. The formation of a dense fibrin clot structure is quite an intense process and packaged in very specific ways. Both E2 and P4 has the ability to shift the haemostatic balance to a hypercoagulable state and therefore viscoelastic studies, morphological analysis as well as turbidimetry were used in this study to observe the possible changes in the fibrin network formation. Viscoelastic studies included thromboelastography (TEG) which gave insight to the properties of clot formation. Morphological studies included scanning electron microscopy (SEM) and atomic force microscopy (AFM) which delivered an investigation in fibrin network morphology, fibrin fiber diameter and surface roughness. Turbidimetry included further analysis of plasma fibrin clot formation and clot lysis time (CLT). Results showed that E2 and P4 showed hypercoagulable viscoelastic properties with decreased fibrin diameter and surface roughness while increased occurrence of dense matted deposits (DMDs) were evident. Turbidimetry showed decreased CLT for E2, but not P4. These results suggest in the presence of endogenous estrogen and progesterone, which is associated with hypercoagulability, the additional burden of synthetic hormones may result in a prothrombotic and hypercoagulable state in females with an inflammatory predisposition. It appears that both E2 and P4, which are known for their anti- and pro-inflammatory action, may influence fibrin network formation on a molecular level. These results are of clinical importance when considering hormones as either a pathological agent or therapeutic intervention.