The pathophysiology of bleeding disorders presenting as abnormal uterine bleeding.
Abnormal uterine bleeding is often the presenting complaint in women with underlying coagulopathies. A clear understanding of the pathophysiology of common bleeding disorders will help the practicing obstetrician/gynecologist in the diagnosis and treatment of these conditions. The normal hemostatic process can be divided into three phases. The first phase, primary hemostasis, consists of platelet adhesion and aggregation. After vascular injury, proteins in the subendothelium are exposed that promote platelet adhesion. Platelet adhesion is uniquely dependent on von Willebrand factor, a plasma protein that serves as a molecular bridge between components of the vessel wall and the platelet glycoprotein Ib/IX receptor. Activation of the adherent platelets promotes additional platelet recruitment, culminating in the formation of the platelet plug. Quantitative or qualitative defects in either the platelet or von Willebrand factor (von Willebrand disease) lead to defective primary hemostasis. Patients present with a prolonged bleeding time and mucocutaneous bleeding manifestations. In the next phase, secondary hemostasis, the plasma coagulation factors are sequentially activated, which leads to fibrin formation and cross-linking. These reactions take place primarily on the surface of activated platelets and are essential in maintaining the stability of the initial platelet plug. Defective secondary hemostasis arises from congenital or acquired deficiencies in coagulation factors. Although these defects are most often associated with bleeding into joints and soft tissues, other manifestations, including abnormal uterine bleeding, may be present. The prothrombin time and the activated partial thromboplastin time serve as initial screening tests for these coagulation disorders, although more specific tests, including factor levels, thrombin time, clot solubility, and mixing studies, are needed to fully define the defect. In the final phase of normal hemostasis, fibrinolysis, the fibrin clot undergoes an orderly process of degradation. Deficiencies in the normal inhibitors of fibrinolysis, such as alpha 2-antiplasmin or plasminogen activator inhibitor-1, may be underdiagnosed causes of delayed bleeding because they are not identified by the usual coagulation screening tests. Disorders of primary hemostasis, including thrombocytopenia and von Willebrand disease, are particularly important to consider when evaluating women with abnormal uterine bleeding. Patients with acquired or congenital deficiencies of either coagulation factors or the regulators of the fibrinolytic system may also present with menorrhagia. Accurate diagnosis of a bleeding disorder is essential to the design of an appropriate therapeutic regimen and is likely to have important clinical implications beyond that of the presenting gynecologic complaint.
Ewenstein
B M
BM
Boston Hemophilia Center, Children's Hospital/Brigham and Women's Hospital, MA 02115, USA.
D001778:Blood Coagulation Disorders / Q000150:complications / Q000503:physiopathology*; D005260:Female; D006801:Humans; D014592:Uterine Hemorrhage / Q000209:etiology*