Prospective data collection on patients with Fibrinogen and Factor XIII deficiencies: design of the PRO-RBDD project


The cross-sectional project entitled "Establishment of an European Network of the Rare Bleeding Disorders (EN-RBD)" ( funded in 2007 by the European Community was established to answer unmet questions on rare bleeding disorders (RBDs). The results of this project increased knowledge on frequency and distribution of each coagulation defect. The EN-RBD database enabled to explore the relationship between the laboratory phenotype and clinical severity of each deficiency, showing that only observed in fibrinogen, FX and FXIII deficiencies there is strong association between plasmatic factor levels and bleeding severity.

The main limitation of this retrospective study was the lack of detailed data on the diagnosis setting and the chronology between diagnosis and bleeding episodes. Therefore there is still a gap in knowledge of annual incidence of either disorders and the bleeding manifestations as well as on what is the minimum coagulant activity level able to prevent spontaneous and trauma/surgery/pregnancy related bleeding and provide an adequate hemostasis.

Therefore, the research group decided to design a project to capture prospective data on patients with the most severe RBDs, fibrinogen and FXIII deficiencies being both conditions suffering from under-reporting.

A dedicated group consisting of specialists in the field and clinical epidemiologists have worked with informational technology team to implement the existing RBDD interactive web-base to include new variables for reaching the current objectives and to allow for data collection at sequential checkpoints (prospective design, PRO-RBDD).

The new database captures data at specific time points for variables including: demographics, racial origin and family studies, genetic, laboratory studies, prophylaxis, bleeding/thrombotic manifestations and their sequelae, obstetric data, surgical bleeding and perioperative data, treatment efficacy and safety. A new section has been added to the database in order to allow prospective data entry. Over three years, there will be 6 data entry time points per patients (i.e. biannual update), although data will be collected also in any other non-scheduled visits.

Several hemophilia treatment centers around the world joined the network and have been collecting data historical data (baseline date) since February 2013. Every six months, follow-up visits will consist of initial screening contact by telephone, performed by experienced clinical study physicians/ nurses, and personal check-up in case of report of (suspected) bleeding episodes or other medical events.

In conclusion, the PRO-RBDD collect prospective data on patients with the two most severe RBDs, fibrinogen and FXIII deficiencies. Once data will be available for these two disorders, hopefully the same model will be extended to different disorders.

This endeavor shall provide essential information on the course and optimal management of these orphan diseases. Moreover the prospective cohort design will allow to define appropriate surrogate end-points to adequately evaluate treatments and particularly the design of new clinical trials and the creation of guidelines for standardized therapeutic approaches.