ORIGINAL ARTICLE Gynaecological The spectrum of haemostatic characteristics of women with unexplained menorrhagia C. H. MILLER, * C. S. PHILIPP,  S. F. STEIN, à P. A. KOUIDES,§ A. S. LUKES, – J. A. HEIT,** V. R. BYAMS,* N. F. DOWLING* and R. KULKARNI*    *Division of Blood Disorders, National Center on Birth Defects and Developmental Disabilities, Centers for Disease Control and Prevention, Atlanta, GA, USA;  UMDNJ-Robert Wood Johnson Medical School, New Brunswick, NJ, USA; àEmory University School of Medicine, Atlanta, GA, USA; §University of Rochester, Rochester, NY, USA; –Duke University, Durham, NC, USA; **Mayo Clinic, Rochester, MN, USA; and   Michigan State University, E. Lansing, MI, USA Summary. While an estimated 13% of women with unexplained menorrhagia have von Willebrand disease (VWD), the frequency of other potential bleeding disorders has been uncertain. This study describes the relatively wide range of laboratory characteristics of women with unexplained menorrhagia and presents issues affecting diagnosis in this population. Women with pictorial blood assessment chart (PBAC) score >100 were identified at six U.S. sites and asked to remain drug free for 10 days prior to testing. Blood was collected on one of the first four menstrual cycle days and tested at a central laboratory for procoagulant factors, VWD and fibrinolytic factors. Platelet function testing by PFA-100 Ò (PFA) and platelet aggregation with ATP release (PAGG/ATPR) were performed locally using standardized methods. Among 232 sub- jects, a laboratory abnormality was found in 170 (73.3%), including 124 of 182 White (68.1%) and 34 of 37 Black (91.9%) subjects; 6.0% had VWD, 56.0% had abnormal PAGG/ATPR, 4.7% had a non-VWD coagulation defect (NVCD) and 6.5% had an abnormal PFA only. AGG/ATPR was reduced in 58.9% of subjects, with multiple agonists in 28.6%, a single agonist in 6.1% and ristocetin alone in 24.2%. Frequencies of PAGG/ATPR defects varied by study site and race; frequencies of VWD and NVCD were similar. Laboratory abnormalities of haemostasis, espe- cially platelet function defects, were common among women with unexplained menorrhagia across multiple U.S. sites. To what degree these abnormalities are clinically significant requires further study. Keywords: bleeding disorders, menorrhagia, platelet func- tion disorders, von Willebrand disease Introduction Unexplained menorrhagia is a common problem that often triggers surgical interventions such as endometrial ablation and/or hysterectomy. If the cause includes an underlying bleeding disorder, such procedures may be unnecessary and might, in fact, pose risks of excessive bleeding and unnecessary use of blood products. Studies designed to assess the prevalence of bleeding disorders among women with unexplained menorrhagia have focused primarily on von Willebrand disease (VWD). The prevalence of VWD is substantial among women with menorrhagia. A review of 11 studies conducted internationally found 131 of 988 women tested (13%) to have VWD, with a 95% confidence interval of 11–15.6% [1]. Testing for other bleeding disorders in this population has not been extensive, and only one study [2] has conducted tests of platelet function beyond performance of a bleeding time. The laboratory evalu- ation of a bleeding patient requires sophisticated and sensitive methods to measure the ability of the platelets to aggregate and to release ATP, as well as a compre- hensive coagulation profile, including fibrinolytic factors. In this study, we noted a wide range of laboratory findings in a group of reproductive age women with unexplained menorrhagia who were comprehensively evaluated for haemostatic abnormalities prior to poten- tial participation in a clinical trial of two treatment methods, desmopressin and tranexamic acid. Results of the treatment trial have been previously published [3]. The study was conducted in a multiracial population Correspondence: Connie H. Miller, PhD, Division of Blood Dis- orders, National Center on Birth Defects and Developmental Disabilities, 1600 Clifton Road, MS D-02, Atlanta, GA 30333, USA. Tel.: +1 404 639 2851; fax: +1 404 639 1638; e-mail: cmiller2@cdc.gov Accepted after revision 29 June 2010 Haemophilia (2011), 17, e223–e229 DOI: 10.1111/j.1365-2516.2010.02382.x Ó 2010 Blackwell Publishing Ltd e223