Plasma-derived human factor X concentrate for the treatment of patients with hereditary factor X deficiency.

INTRODUCTION: Hereditary factor X (FX) deficiency (HFXD) is an autosomal recessive rare bleeding disorder that leads to defects in the FX protein. Depending on the degree of deficiency, patients may be at risk of life-threatening bleeding episodes. Historical treatments for FX deficiency include prothrombin complex concentrates, which can increase the risk of thrombosis, and fresh frozen plasma, which can cause volume overload and transfusion reactions. Plasma-derived FX (pdFX), a single-factor, high-purity, high-potency human FX treatment, was approved in 2015 in the United States and in 2016 in Europe for on-demand treatment and prophylaxis of bleeding episodes and perioperative management of patients with HFXD. METHODS: Five studies that examined the use of pdFX in patients with mild (plasma FX activity [FX:C] ≥5 IU/dL), moderate (FX:C ≥1 and <5 IU/dL), or severe (FX:C < 1 IU/dL) HFXD were reviewed: TEN01, TEN02 and TEN03 were prospective, open-label, multicentre, nonrandomised studies, and TEN05 and TEN06 were multicentre retrospective studies. RESULTS: When used as an on-demand treatment, pdFX was judged by investigators to be successful in treating 41/42 (97.6%), 2/3 (66.6%) and 79/79 (100%) bleeds in TEN01, TEN02 and TEN05, respectively. When used prophylactically, pdFX was judged 'excellent' for the prevention of bleeds in nine (100%) and eight (100%) patients in TEN02 and TEN05, respectively. Perioperative treatment and pharmacokinetics were also assessed. pdFX was safe and well tolerated. CONCLUSIONS: Together, these studies support the use of pdFX for on-demand treatment of bleeding, routine prophylaxis, and perioperative management of bleeding in patients with HFXD.

Occurrence and management of severe bleeding episodes in patients with hereditary factor X deficiency.

Vitamin K-dependent factor X (FX) plays an important role in thrombin formation, and a deficiency in FX can cause impaired coagulation, the severity of which is usually correlated with the degree of deficiency. Due to the critical role that FX plays in the coagulation cascade, FX deficiency is associated with a higher risk of bleeding than deficiencies in other coagulation factors. Patients with the hereditary autosomal-recessive homozygous form of FX deficiency, which occurs in approximately 1:1,000,000 individuals worldwide, are often diagnosed when they present with spontaneous life-threatening haemorrhage (most often intracranial haemorrhage) during the first month of life. In addition to central nervous system bleeds, other severe bleeding types experienced by such patients may include umbilical cord bleeding, gastrointestinal or pulmonary haemorrhage, intramuscular haematomas and/or haemarthrosis. Delayed treatment or inadequate replacement of FX may result in developmental delays, musculoskeletal disabilities or death. The high risk of recurrent severe bleeding necessitates prophylactic replacement therapy for many individuals with severe FX deficiency. Available products for replacement therapy include plasma-derived FX concentrate and prothrombin complex concentrates. Fresh-frozen plasma may be used when concentrates are not available but is a less efficient means of FX replacement. This article reviews the literature on severe bleeding in individuals with hereditary FX deficiency and discusses current treatment options.