ANALISI DEI PROBLEMI GINECOLOGICI ED OSTETRICI NELLE DONNE CON COAGULOPATIA A DIATESI EMORRAGICA ATTRAVERSO IL REGISTRO INTERNAZIONALE (WRBDD).

SUMMARY Patients affected by bleeding disorders present a wide spectrum of clinical symptoms that vary from mild or moderate bleeding tendency to significant episodes. Women with inherited bleeding disorders are particularly disadvantaged since in addition to suffering from general bleeding symptoms they are also at risk of bleeding complications from regular haemostatic challenges during menstruation, pregnancy and childbirth. Moreover, such disorders pose important problems for affected women due to their reduced quality of life caused by limitations in activities and work, and alteration of their reproductive life. These latter problems include excessive menstrual bleeding or menorrhagia, miscarriage, bleeding complications during pregnancy and after delivery and their related complications such as acute or chronic anaemia. Moreover, reliable information on clinical management are scarce, only a few available long term prospective studies of large cohorts provide evidence-based guideline about diagnosis and treatment. To this end, the University of Milan has created a working group on menorrhagia and other gynecological problems in women with rare bleeding disorders (WRBD: http://www.wrbd.org/network.htm) involving worldwide renewed centers besides the Angelo Bianchi Bonomi Hemophilia and Thrombosis Centre of Milan. A prospective study recruiting women with confirmed diagnosis of von Willebrand disease (VWD), rare coagulation disorders (RBDs: rare bleeding disorders) and platelet disorders was designed. Women without evidence of coagulation disorders constituted the control group. The aim of this project was to retrospectively and prospectively collect a large cohort of women to: - evaluate the prevalence of gynaecological problems (menarche, ovulation bleeding, menorrhagia, bleeding during pregnancy and postpartum bleeding) - evaluate the association between menstrual loss and clinical severity (other bleeding symptoms) - evaluate the association between clinical severity and phenotype results - to collect and analyse data on concomitant gynaecological abnormalities, complications of menorrhagia (anaemia), requirement of gynaecological intervention and to evaluate the occurrence of abortion, miscarriage and other pregnancy complications. A specifically tailored questionnaire was used to collect data, along with the Bleeding Score (BS) quesstionnaire, capable of translating the hemorrhagic history of the subject in a numerical coefficient, and the pictorial blood assessment chart (PBAC), graphical tool that scores the intensity of menstrual flow, thus defining the severity of menorrhagia. The collected data have been then entered into a database specifically created to obtain a complete and extensive amount of information which will ultimately be able to extrapolate the clinical information necessary for the intended purposes. After the first year, 231 patients were enrolled in the study: 113 (48.9%) patients were affected with VWD, 38 (16.5%) with RBDs and 80 (34%) were controls for a total of 214 pregnancies. Our data showed that menorrhagia was a specific symptom of women with VWD, while the profuse menarche and intermittent and heavy menstrual bleeding seemed to be a symptom of women with RBDs. However, the intra-abdominal bleeding and the vaginal bleeding near ovulation seem not to be specifically related to the presence of hemorrhagic disease, confirming currently available data from the literature. Similarly, hemorrhagic complications during surgery do not seem to have a higher incidence in the presence of VWD or RBDs compared with controls, but we consider that these data needs to be further analyzed after further enlargement of the sample size in order to discriminate the population in two groups: with and without prophylaxis preopaeratoria. The results of the study did not detect significant differences between the two groups (women with VWD and RDBs) and the general population with regard to the rate of spontaneous abortions, intrauterine deaths and the incidence of bleeding occurring during pregnancy, confirming the data of the current literature. Hemorrhage after vaginal delivery was, however, the only hemorrhagic complication showing a significantly higher incidence in the two groups of patients compared with controls. In particular secondary postpartum haemorrhage was higher in women with VWD compared to controls. BS and PBAC in our study were also tested for their potential for predicting the phenomenon of bleeding the patient. The PBAC showed to have a predictive value on the profuse menarche in the group of women with RBDs (threshold value 606.5) and acute hemorrhagic event and bleeding near ovulation in women with VWD (threshold value 737 and 682.5, respectively). Both scoring systems were found to predict the postpartum bleeding in women with VWD: a BS higher than 11 seemed to be associated to a 3-fold increased risk of postpartum bleeding, whereas a PBAC higher than 200 to a 18-fold increased risk. The coagulant activity level of the deficient factor was shown to be a predictive tool for hemorrhagic event at menarche and for the acute bleeding in women with VWD (24.5 and 17.5, respectively; threshold value 22) and for the acute bleeding in women with RBDs (threshold 27). It was also shown to be associated to postpartum hemorrhage in women with VWD (an activity level less than 23% was associated to a to 6-fold higher risk). In conclusion, our results, although preliminary have considerable importance as an outcome of a collaborating data collection project, using an ad hoc database, whose final validation will happen in the course of study with the ultimate goal of providing all the necessary features to make it maximally effective and accurate. Eventually, the analysis of data collected will provide a suitable substrate for the drafting of guidelines for the universal prophylactic and therapeutic approach to obstetricians hemorrhagic gynecological problems.