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.
