Changes in Bleeding and Clotting During the Menstrual Cycle
Changes in Bleeding and Clotting During the Menstrual Cycle
Indirect evidence suggests that hormonal fluctuations during the menstrual cycle also affect
 the bleeding and clotting system. This study looks at two sensitive laboratory tests at four
 time points during the menstrual cycle to determine if there is a natural variation in
 coagulation and platelet function. Laboratory tests in healthy subjects will be compared to
 women with von Willebrand's disorder type 1, a bleeding disorder. In the future, these
 laboratory tests may help in the diagnosis of bleeding and clotting disorders and to design
 treatments for women with abnormal menstrual bleeding.
Von Willebrand disease (VWD) is the most common hereditary bleeding disorder, occurring in
 1-2% of the population. Menorrhagia, or heavy menstrual bleeding, occurs in the majority of
 women with von Willebrand disease (VWD) and adversely affects quality of life. The American
 College of Obstetrics and Gynecology has recommended that women with heavy menstrual bleeding
 have diagnostic testing for VWD. Unfortunately, the diagnosis of VWD in women with
 menorrhagia can be difficult due to fluctuations in hemostatic protein levels during the
 menstrual cycle. The lack of useful coagulation assays has also limited the scope of
 pharmacokinetic studies and comparative clinical trials needed to determine best clinical
 practices in women with VWD.

 Two new assay systems offer a possibility of increased sensitivity to physiologic variations
 in coagulation and fibrinolysis. The calibrated automated thrombin generation assay (TG), an
 estimation of endogenous thrombin potential (ETP), measures generation of thrombin throughout
 the entire process of coagulation and has appears to be very sensitive to small changes in
 levels of coagulation proteins. Thromboelastography (TEG) records clot formation and
 dissolution in whole blood samples providing a good marker for fibrinolysis. We propose that
 TG and TEG will be more sensitive than traditional coagulation assays to detect physiologic
 variations in hemostasis during the menstrual cycle and can accurately diagnose VWD. This is
 a single-institution pilot study to identify trends which are worthy of further exploration
 in a larger multi-institutional study. Our primary objective is to describe characteristics
 of TG and TEG at 4 time points during the menstrual cycle (days 0-3, 7-10, 14-17, and 21-24).
 Our secondary goal is to quantify the effects of VWD on TG and TEG at the same time points
 during the menstrual cycle and compare these to traditional coagulation assays.

 This will be a single-institution pilot study of a total of 40 subjects: 20 healthy women and
 20 women with VWD. Subjects must be female between the ages of 18 and 50 years, have regular
 menstrual periods, and not be pregnant. Women who are taking hormonal therapy,
 anti-fibrinolytic therapy, hemostatic agents or anti-platelet agents, will not be eligible
 for participation. Subjects will be given tampons and/or pads to use during one menstrual
 cycle. Study participation will involve a brief interview, completion of a questionnaire and
 a pictorial chart of one menstrual cycle, and having blood drawn at 4 time points during one
 menstrual cycle. Blood samples will be collected for TG and TEG and standard assays of
 coagulation and fibrinolysis. TG and TEG measurements will be compared to standard measures
 of coagulation, fibrinolysis, and platelet activation markers. Serum from the visit on day
 21-24 will be tested for progesterone and Bhcg to confirm ovulation and exclude pregnancy.
 All assays will be performed at the Gulf States Hemophilia & Thrombophilia coagulation
 laboratory.

 This study will result in an improved capability to diagnose women with VWD during the
 menstrual cycle. These new assays may be useful in the rational design of therapeutic agents
 and clinical trials. In addition, the physiologic basis of variations in coagulation during
 the menstrual cycle can be explored in future studies using this assay system.
Inclusion Criteria:

 -  Must be female

 -  Aged 18 to 50 years, with regular menstrual cycles.

 -  Healthy volunteers and women with von Willebrand's disorder are both being recruited.

 Exclusion Criteria:

 -  Pregnancy

 -  Use of hormonal therapy including birth control pills

 -  Use of hemostatic agents such as DDAVP or anti-platelet agents.