RARE INHERITED COAGULATION DISORDERS: CLINICAL AND MOLECULAR CHARACTERIZATION TO DEVELOP A NATIONAL REGISTRY AND MOLECULAR TESTS FOR PRENATAL DIAGNOSIS

Normal blood coagulation is a complex process involving as many as 20 different plasma proteins known as blood clotting factors. Normally, these factors interact to form the haemostatic plug. When one coagulation factor is deficient, the process is impaired and bleeding problems arise. Some bleeding disorders are caused by inherited disorders, the more frequent are haemophilias and von Willebrand disease. Besides these well known diseases, other coagulation factor deficiencies exist. These are called Rare Inherited Coagulation Disorders (RICDs) and have an incidence of only 0.5-2 individual per million. Patients affected by RICDs suffer from hemorrhagic episodes ranging from ecchymosis and nose bleeding to life-threatening gastrointestinal and central nervous system bleedings. Although RICDs are not common, they are life-long, complex, and can have an impact on the physical, psychosocial, and economic well being of the patient. All conditions can be treated with clotting factor concentrates, except FV deficiency, for which therapy still depends on fresh frozen plasma. The rarity of these disorders results in a lesser knowledge on the type and severity of symptoms, on the underlying genetic defects and on the actual therapy. Moreover, for each coagulopathy, most mutations unique for any given patient, requiring a cumbersome analysis at the DNA level to identify the specific mutation in each affected family. The main aim of this research project is to improve knowledge on these rare genetic diseases. Through the available clinical network AICE (Associazione Italiana centri Emofilia) we will collect and analyze virtually all Italian patients affected by RICDs. The genetic basis of the disease will be studied in detail in each patient. Clinical and molecular data will be channeled into an Italian Registry on RICDs. This information will be useful to improve clinical diagnosis and management of bleeding episodes and to allow prenatal diagnosis in families who so desire.