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Breast cancer (BC) is one of the most prevalent forms of cancer in women worldwide. Clinical research indicates that BC patients are at an increased risk for thrombotic events, drastically decreasing their quality-of-life and treatment outcomes. There is ample evidence of this in the literature, but it is mainly focused on metastatic BC. Therefore, coagulopathies of nonmetastatic BC are understudied and require in-depth investigation. In this study, clot kinetics and ultrastructure were used to investigate treatment-naïve, nonmetastatic BC patients using scanning electron microscopy, Thromboelastography®, and confocal laser scanning microscopy. It was demonstrated that nonmetastatic BC patients exhibit minimal ultrastructural alterations of the clot components and no changes in the clot kinetics. However, BC patients presented changes to fibrinogen protein structure, compared to matched controls, using an amyloid-selective stain. Together, these findings suggest that coagulation dysfunction(s) in BC patients with early disease manifest at the microlevel, rather than the macrolevel. This study presents novel insights to a method that are more sensitive to coagulation changes in this specific patient group, emphasizing that the coagulation system may react in different forms to the disease, depending on the progression of the disease itself.
Combined oral contraceptives (COCs) are commonly prescribed and increase the risk of venous thromboembolism (VTE). We have previously found that two COCs, both containing drospirenone (DRSP) and ethinyl estradiol (EE), cause spontaneous fibrin formation in whole blood. The aim of this study was, therefore, to use platelet-poor plasma (PPP) from the same cohort of DRSP/EE users to determine the impact of these COCs on the fibrin component, specifically the fibrin clot viscoelasticity, turbidimetry, and biophysical traits. PPP from 25 females per test group and a control group (n = 25) were analyzed using thromboelastography (TEG), turbidimetry, and scanning electron microscopy. The results highlight abnormal fibrin clot formation, lysis, and architecture; DRSP/20EE showed the greatest effect. DRSP/EE use increased the fibrin fiber diameter and showed dense matted clots. Only when the influence of COCs on the structural properties and behavior of fibrin fibers during thrombus formation and lysis is better understood are we able to predict and prevent coagulopathies associated with these synthetic hormones. Clinical practitioners should take this into consideration for female patients that either have comorbidities, which could burden the coagulation system, or may be exposed to external factors that could increase their risk for VTE.
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/20 µg EE and 3 µg DRSP/30 µg 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.
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