Clinical meaning
Abnormal uterine bleeding (AUB) is classified using the FIGO PALM-COEIN system, which divides causes into structural (PALM: Polyp, Adenomyosis, Leiomyoma, Malignancy/hyperplasia) and non-structural (COEIN: Coagulopathy, Ovulatory dysfunction, Endometrial, Iatrogenic, Not yet classified).
Normal endometrial hemostasis depends on a precise balance between vasoconstriction, platelet aggregation, coagulation, and fibrinolysis. During menstruation, spiral arteriolar vasoconstriction limits blood loss, while tissue factor (TF) activates the coagulation cascade locally. Endometrial fibrinolytic activity (tissue plasminogen activator, tPA) is regulated to allow orderly tissue shedding. The endometrium regenerates from the basalis layer under estrogen stimulation.
In AUB-E (endometrial causes), molecular defects in local hemostatic mechanisms include increased endometrial fibrinolysis (elevated tPA and reduced PAI-1), deficient endothelin-1 (ET-1) mediated vasoconstriction, and altered prostaglandin ratios (increased PGE2 and prostacyclin relative to PGF2α and thromboxane A2). This shifts the hemostatic balance toward excessive bleeding.
In AUB-O (ovulatory dysfunction), anovulation results in unopposed estrogen exposure. Without progesterone-mediated secretory transformation, the endometrium undergoes prolonged proliferation, becoming fragile and vascular. Disordered shedding produces irregular, heavy, and prolonged bleeding. Chronic unopposed estrogen also increases the risk of endometrial hyperplasia (with or without atypia) and progression to endometrial carcinoma.
AUB-C (coagulopathy) accounts for approximately 13% of heavy menstrual bleeding. Von Willebrand disease is the most common inherited bleeding disorder causing AUB, followed by platelet function defects and coagulation factor deficiencies.