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.

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.

Use of a Sentinel Lymph Node Biopsy Algorithm in a South African Population of Patients With Cervical Cancer and High Prevalence of Human Immunodeficiency Virus Infection.

OBJECTIVES: Cervical cancer is common in resource-poor settings with high prevalence of tuberculosis, pelvic inflammatory disease, and human immunodeficiency virus (HIV) infection. There are no data regarding the sentinel lymph node (SLN) algorithm in these high-risk cancer populations. Our objectives were to establish the sensitivity, specificity, positive predictive value, and negative predictive value of the SLN algorithm in cervical cancer and to compare the detection rate of indocyanine green (ICG) versus blue dye versus technetium Tc 99m nanocolloid (Tc). METHODS: This prospective study was conducted at the University of Pretoria. Tc-nanocolloid tracer, ICG dye, and methylene blue (MB) were used to detect SLNs. Pathological ultrastaging was performed on hematoxylin-eosin- negative nodes. RESULTS: Results of 72 women were analyzed. The mean age was 47.2 years, 5.5% had a history of tuberculosis, 18.1% had pelvic inflammatory disease, and 65.3% were HIV positive. The SLN detection rate was 65.3%. Detection rate of MB was 56.9%; Tc, 69.4%; ICG, 87.5%; and the combination of MB and Tc, 91.7%. Pelvic nodal metastases occurred in 26.4%. The sensitivity, specificity, negative predictive value, and positive predictive value of SLN biopsy were 85.7%, 100%, 100%, and 98.33%, respectively. The false-negative rate was 14.3%, and it was 0% if the algorithm was applied. CONCLUSIONS: The SLN algorithm is a feasible option for use in cervical cancer women with a high prevalence of HIV infection. The detection rate is generally lower, but in select subgroups of women, it was comparable to that reported elsewhere. This is the first report of the use of SLN biopsy in a substantial group of HIV-infected women.

The impact of childbirth on pelvic floor morphology in primiparous Black South African women: a prospective longitudinal observational study.

INTRODUCTION AND HYPOTHESIS: There is a lack of prospective studies evaluating the impact of childbirth on the pelvic floor in non-white populations. We intended to study delivery-related changes in pelvic floor morphology in Black South African primiparae. We also intended to determine the impact of anatomical changes on symptoms in the postpartum period. METHODS: A total of 153 nulliparous women between 35 and 39 weeks gestation were recruited from a district antenatal clinic. All women had a standardized interview, completed the International Consultation on Incontinence Vaginal Symptoms questionnaire followed by three/four dimensional transperineal ultrasonography. This was repeated at 3-6 months postpartum. RESULTS: Of the 153 women, 84 (54.9%) returned at a mean of 4.8 months postpartum. Of these women, 60 (71.4%) had a vaginal delivery and the remainder a caesarean section (20 emergency and 4 elective). Overall, there were statistically significant increases in bladder neck descent (P = 0.003), pelvic organ descent and levator hiatal distensibility (all P < 0001) at the postpartum assessment. Levator avulsion was diagnosed in nine (15%) of those delivered vaginally. Postpartum vaginal laxity was the commonest bothersome vaginal symptom, reported by 51 women (60.7%). CONCLUSIONS: There is significant alteration in pelvic organ support and levator hiatal distensibility postpartum, with more marked effects in women after vaginal delivery. Of Black primiparous women, 15% sustained levator trauma after their first vaginal delivery.

Part 2: ultrastructural changes of fibrin networks during three phases of pregnancy: a qualitative investigation.

INTRODUCTION: Normal pregnancy is characterized by significant alterations in the haemostatic system accompanied by an augmented risk of thrombosis. MATERIALS AND METHODS: The fibrin network ultrastructure of different phases of pregnancy, namely early pregnancy (week 8-14), late pregnancy (week 36-40) as well as post-partum (week 6-8 after birth) were compared with nonpregnant fibrin networks as well as each other to establish whether differences in fibrin network morphology exist during pregnancy. Scanning electron microscopy was employed to analyse fibrin network morphology. RESULTS: The fibrin networks from all phases of pregnancy appeared similar to each other, exhibiting prominent coagulant formation, an increase in the formation of minor, thin fibers, and the presence of granular globules. All three phases, however, differ from the typical fibrin network ultrastructure exhibited by the fibrin networks from nonpregnant individuals. The increase in estrogen associated with pregnancy may cause the increase in coagulation factors and ultimately the prothrombotic state characteristic of pregnancy. CONCLUSIONS: Since no differences were apparent between the different phases of pregnancy it suggests that activation of the coagulation system commences with pregnancy and this pro-thrombotic state continues till at least 8 weeks after birth. These results may shed light on possible pathological mechanisms employed in the development of abnormal or ailing pregnancy.

Estrogen causes ultrastructural changes of fibrin networks during the menstrual cycle: a qualitative investigation.

INTRODUCTION: Hormonal fluctuations may influence fibrin structure. During the menstrual cycle, plasma fibrinogen levels change, mainly due to the variations of estrogen. Throughout the menstrual cycle estrogen levels peak twice, first during the mid-follicular phase and then a lower second peak during the luteal phase. MATERIALS AND METHODS: In order to investigate the possible changes in the fibrin network throughout the menstrual cycle, the fibrin network ultrastructure of six healthy female participants were studied at different intervals in the menstrual cycle where differences in estrogen levels are prevalent. Blood plasma smears were prepared for scanning and transmission electron microscopy analysis. RESULTS: The external and internal structure of the fibrin fibers showed different morphologies throughout the menstrual cycle. The fibrin fibers were smooth during days 1-5. However, during days 12-14 of the menstrual cycle the fibrin fiber morphology started to change, becoming less smooth. During the luteal phase of the cycle (days 20-25), the network appears sticky, where the minor, thin fibers are more prominent between the thick fibers when compared to the menstrual phase. CONCLUSION: The two estrogen peaks of the menstrual cycle coincide with the changes seen in the current qualitative research, where the fibrin morphology changes during the same time as the estrogen peaks occur. Purified fibrinogen confirmed that it is indeed estrogen that causes the altered fibrin network morphology. This research is the first to show ultrastructural changes in fibrin fiber morphology resulting from estrogen changes during the menstrual cycle.