Endometrial haemostasis and menstruation

Abstract

Under normal physiological circumstances menstruation is a highly regulated, complex process that is under strict hormonal control. During normal menstruation, progesterone withdrawal initiates menstruation. The cessation of menstrual bleeding is achieved by endometrial haemostasis via platelet aggregation, fibrin deposition and thrombus formation. Local endocrine, immunological and haemostatic factors interact at a molecular level to control endometrial haemostasis. Tissue factor and thrombin play a key role locally in the cessation of menstrual bleeding through instigation of the coagulation factors. On the other hand, fibrinolysis prevents clot organisation within the uterine cavity while plasminogen activator inhibitors (PAI) and thrombin-activatable fibrinolysis inhibitors control plasminogen activators and plasmin activity. Abnormalities of uterine bleeding can result from imbalance of the haemostatic factors. The most common abnormality of uterine bleeding is heavy menstrual bleeding (HMB). Modern research has shown that an undiagnosed bleeding disorder, in particular von Willebrand disease (VWD) and platelet function disorders, can be an underlying cause of HMB. This has led to a change in the approach to the management of HMB. While full haemostatic assessment is not required for all women presenting with HMB, menstrual score and bleeding score can help to discriminate women who are more likely to have a bleeding disorder and benefit from laboratory haemostatic evaluation. Haemostatic agents (tranexamic acid and DDAVP) enhance systemic and endometrial haemostasis and are effective in reducing menstrual blood loss in women with or without bleeding disorders. Further research is required to enhance our understanding of the complex interactions of haemostatic factors in general, and specifically within the endometrium. This will lead to the development of more targeted interventions for the management of abnormal uterine bleeding in the future.

Thrombin generation in different cohorts: Evaluation of the haemostatic potential

“…A highly active fibrinolytic process participates in the regulation of normal menstruation. Large amounts of fibrin and fibrin degradation products are found in the menstrual fluid; in this study, higher D-dimer was found during the early follicular phase, which corresponds to the menstruation phase of the uterine cycle [97,101], suggesting systemic rather than local hyperfibrinolytic activity.…”

“…During menstruation, the cessation of bleeding is achieved by platelet aggregation, fibrin deposition and thrombus formation [101]. TF and its binding to circulating FVIIa for the formation of the TF/FVIIa complex is central to the endometrial haemostasis, as in the systemic haemostasis.…”

“…Additionally, intact haemostatic potential is essential for the control of menstrual bleeding, including cessation of bleeding [101]. This knowledge has lead to a number of studies attempting to evaluate the physiological changes in the coagulation system during the menstrual cycle.…”

Less abnormal uterine bleeding with dabigatran than warfarin in women treated for acute venous thromboembolism

“…One recent study suggests that warfarin suppresses thrombin generation more efficiently than dabigatran [16]. Because thrombin plays a key role locally in the uterus endometrium in the cessation of menstrual bleeding, the difference in suppression of thrombin generation may explain, although this is speculative, why dabigatran was associated with less AUB than warfarin [17,18] Of note, differences in suppression of other hemostatic mechanisms by dabigatran vs. warfarin may further contribute to the observed differences in the occurrence of our primary endpoint [16]. The mechanism explaining a potentially different effect on menstrual bleeding of FXa inhibitors, notably rivaroxaban, and thrombin inhibitors remains unknown.…”

Hormonal Contraception as Treatment for Anomalous Uterine Bleeding

“…Непосредственной причиной кровотечений стано-вятся расстройства сосудистого гомеостаза и репаратив-ных процессов в эндометрии, которые возникают вто-рично при наличии структурной патологии или любых других причин, действующих за пределами эндометрия, и первично при независимой эндометриальной дис-функции [8]. В свою очередь, расстройства сосудистого гомеостаза и репарации обусловливаются многими фак-торами, в числе которых персистирующее воспаление, дисбаланс вазоконстрикторных и вазодилататорных простагландинов (увеличение локального синтеза про-стагландина E 2 и простациклина), активация процессов локального фибринолиза, усиление ангиогенеза с повы-шением плотности сосудов, рост содержания оксида азота (антиагреганта и вазодилататора), ускоренный лизис образующихся во время менструации сгустков крови в результате избыточной продукции активатора плазминогена и др.…”