The Impact of Two Combined Oral Contraceptives Containing Ethinyl Estradiol and Drospirenone on Whole Blood Clot Viscoelasticity and the Biophysical and Biochemical Characteristics of Erythrocytes

Abstract

Venous thrombosis is associated with combined oral contraceptive (COC) use. We investigated the impact of two ethinyl estradiol (EE) and drospirenone (DRSP) containing COCs (3 mg DRSP/20µg EE and 3µg DRSP/30µg EE) on the viscoelasticity of whole blood clots along with the biophysical and biochemical characteristics of erythrocytes. Thromboelastography (TEG) analysis showed a tendency toward a hypercoagulable state in the COCs groups that was more pronounced with higher EE concentrations. Light microscopy and scanning electron microscopy (SEM) showed rouleaux formation of erythrocytes and alterations to the erythrocyte shape for both COC groups, which was attributed to membrane damage. SEM analysis showed spontaneous activation of fibrin and platelets in the COC groups, along with interactions between erythrocytes and platelets and/or fibrin. Confocal microscopy confirmed compromised membrane integrity in the COC groups compared to controls. Global thrombosis test analysis showed increased platelet activation and low thrombolysis in both COC groups when compared to controls. In conclusion, DRSP/EE formulations impact erythrocytes’ biophysical and biochemical properties to cause a shift in hemostasis to a prothrombotic state. Although these effects are mostly subclinical the long-term effects and risks involved with the use of these hormones should be considered carefully for each individual.

Mechanical and Physical Behavior of Fibrin Clot Formation and Lysis in Combined Oral Contraceptive Users

“…It appears that the presence of red blood cells and platelets, therefore, masked the true effect of these hormones on the coagulation factors, specifically fibrin. Spontaneous fibrin formation observed with SEM analysis of whole blood, however, indicated that the fibrin component was, in fact, significantly affected (Emmerson et al, 2018), emphasizing the need for a multidisciplinary approach when investigating coagulopathy.…”

“…When we examined the whole blood viscoelasticity of this same cohort of DRSP/EE female users, only three parameters showed significant results, namely the R, α , and TMRTG. DRSP/30EE showed the greatest variation in these, indicating that the higher EE concentration had the greatest influence on the initiation time as well as the rate at which the thrombus forms due to an increase in the thrombin burst (Emmerson et al, 2018). On the other hand, the majority of the viscoelastic parameters were significantly influenced by DRSP/EE use in the PPP samples, with the lowest dose having the greatest effect; this indicates that the fibrin component is severely affected by these hormone formulations.…”

“…The same cohort of DRSP/30EE and DRSP/20EE users, as well as controls, was enrolled as previously described (Emmerson et al, 2018). In this observational case study (REC/IRB No.…”

“…Venous clots are referred to as “red clots” due to their high fibrin and erythrocyte content (Aleman et al, 2014). We have previously investigated the impact of DRSP/EE formulations on whole blood viscoelasticity, where specifically erythrocytes visualized by scanning electron microscopy (SEM) (Emmerson et al, 2018), showed spontaneous fibrin formation and, thus, indicated that these oral contraceptives affect the fibrin component. Since very little is known about the effect that DRSP/EE formulations have on the biophysical properties of fibrin in healthy young women, the aim of this study was, therefore, to compare platelet-poor plasma (PPP) from the same DRSP/20EE and DRSP/30EE cohort to determine the impact of these COCs on the fibrin clot viscoelastic, turbidimetry, and biophysical traits.…”

Thrombosis and Gestagens

“…Следовательно, комбинация дроспиренона и ЭЭ влияет на биофизические и биохимические свойства эритроцитов, вызывая переход гемостаза в протромботическое состояние. Хотя выявленные эффекты в основном являются субклини ческими, долгосрочные эффекты и риски, связанные с использованием этих гормонов, должны тщательно рассмат риваться для каждой женщины [38].…”