EAPHEMOLEVEN® Expanded Access Program for Prevention of Surgical and Postpartum Hemorrhage in Patients With Severe Inherited Factor XI Deficiency

Many patients are asymptomatic until hemostatically challenged by surgery or trauma; so, the diagnosis is often made in late childhood or early adulthood but always after full liver maturation (i.e. 6 months) as reported by Andrew et al. Spontaneous bleeding is rare, except menorrhagia, and bleeding occurs mainly after surgery or injury. Bleeding is observed mainly in surgical sites with high fibrinolytic activity such as mouth, nose, or the genitourinary tract. Pregnancy, labor and delivery can also be challenging for women with FXI deficiency. In 1999 a study published in the American Journal of Hematology revealed that FXI levels are inconsistent during pregnancy. The incidence of postpartum hemorrhage is increased in women with factor XI deficiency. The incidence is 16% for the primary postpartum hemorrhage in FXI patients, compared with 5% in the general population. Moreover, the incidence is 24% for the secondary postpartum hemorrhage in comparison with that in the general obstetric population (0.7%). The authors recommend that FXI levels be obtained during the initial visit and monitored during the woman's third trimester. For all of these reasons it is important for women who suspect they might have a FXI deficiency to be tested and diagnosed before pregnancy. Severe factor XI deficiency is defined by levels of <0.20 IU/mL. Such individuals have a high probability of post-operative hemorrhage. Individuals with levels between 0.20 IU/mL and the lower limit of the normal range, generally 0.65-0.80 IU/mL, are generally classified as having partial or mild deficiency with a lower risk of post-operative bleeding. Partial deficiency is being increasingly recognized following pre-operative tests or as a result of family screening. Thus partial factor XI deficiency is often diagnosed in asymptomatic individuals, creating management dilemmas because of the unpredictability of the bleeding risk. To differentiate an isolated or combined bleeding disorder in a patient with factor XI deficiency, other causes of bleeding should be investigated and excluded (e.g. von Willebrand disease, platelet disorders).