Potential of the Community Counts registry to characterize rare bleeding disorders.

INTRODUCTION: Rare bleeding disorders (RBDs) comprise of heterogeneous coagulation factor deficiencies and platelet disorders that are underreported worldwide. AIM: First report on RBD data from United States haemophilia treatment center network (USHTCN). METHODS: A national surveillance system for the federally recognized USHTCN developed in collaboration with the Centers for Disease Control and Prevention (CDC) and American Thrombosis and Haemostasis Network (ATHN) was queried for patients with RBDs. Patient counts were extracted from the HTC Population Profile (HTC PP) component including limited data on patients followed through the USHTCN, and from the Registry component, including patient authorized, detailed clinical data. The prevalence of RBDs in the United States was estimated based on the HTC PP data and compared to the expected national prevalence based on data extrapolated from Orphanet, an international registry. RESULTS: Based on the estimated prevalence of RBD in the overall 2017 US population, the cases in the HTC network were lower than expected for FI, FII, FX, and FV + FVIII deficiencies by 36%, 61%, 75% and 94%, respectively, and higher than expected for FXIII, FV, FVII, and FXI deficiencies by 7%, 14%, 33% and 185%, respectively. The proportion of RBD patients reported in the HTC PP, enrolled in the Registry, was 10.8%. CONCLUSIONS: There is a clear need to identify individuals with RBDs who could benefit from the comprehensive care provided in the USHTCN. In addition, increased enrolment of people with all RBDs in the Registry is needed to improve knowledge of treatment outcomes of patients with RBDs in the United States.

Plasma-derived human factor X concentrate for on-demand and perioperative treatment in factor X-deficient patients: pharmacology, pharmacokinetics, efficacy, and safety.

INTRODUCTION: Hereditary factor X (FX) deficiency is a rare autosomal recessive bleeding disorder characterized mainly by mild-to-severe bleeding into the mucous membranes, muscles or joints. Previously, treatment options for hereditary FX deficiency were limited mostly to products that may not specify FX content (i.e. fresh frozen plasma and prothrombin complex concentrates) and that have associated safety concerns. To meet the need for a single-factor replacement therapy specifically for use in FX-deficient patients, a high-purity, high-potency, human plasma-derived FX concentrate (pdFX; Coagadex®; Bio Products Laboratory, Elstree, UK) has been developed and approved for treatment of perioperative bleeding and on-demand treatment in FX-deficient patients. Areas covered: The pharmacology, efficacy, and safety of pdFX are discussed, with a review of preclinical studies and clinical trial data that led to regulatory approval of pdFX in the United States and Europe. Expert opinion: As the first single-factor replacement therapy indicated for hereditary FX deficiency, pdFX is a safe and efficacious treatment option in patients aged ≥12 years with hereditary FX deficiency. Clinical studies of pdFX provide a dosing regimen for use in cases of bleeding episodes, surgery, and prophylaxis. Further studies are ongoing regarding use of pdFX long term and in patients aged ≤12 years.

Development of long-acting recombinant FVIII and FIX Fc fusion proteins for the management of hemophilia.

INTRODUCTION: Prophylactic treatment with replacement clotting factor is the recommended regimen for patients with severe hemophilia to prevent bleeding episodes. However, currently available replacement clotting factors are limited by their relatively short half-lives and require intravenous injections up to three times weekly to maintain protective levels, which can impact compliance and, thus, patient outcomes. AREAS COVERED: The potential advantages of long-acting coagulation factors, including reduced injection frequency, increased treatment adherence, and improved clinical outcomes, are discussed. Fragment crystallizable (Fc) fusion technology is introduced and the development of long-acting recombinant factor VIII Fc (rFVIIIFc) and recombinant factor IX Fc (rFIXFc) fusion proteins for the treatment of hemophilia A and B, respectively, are described. Preclinical and clinical studies of rFVIIIFc and rFIXFc showing improved pharmacokinetics over currently available products are reviewed. EXPERT OPINION: Long-acting coagulation factors, including rFVIIIFc and rFIXFc, have the potential to change current paradigms of care for hemophilia A and B, respectively. Less frequent infusions may provide prolonged protection from bleeding and bleed resolution with fewer injections. In addition, long-acting coagulation factors provide an opportunity for improved individualized treatment for hemophilia.

Priming correct information reduces the misinformation effect.

The misinformation effect is a well-established phenomenon in the false memory literature, although the mechanisms that underlie it are debated. In the present study, we explored one aspect of the controversy, the fate of the original memory. We began from an activation-based view of memory, capitalizing on the well-understood processes of associative priming and spreading activation, to test the hypothesis that true and suggested information can coexist in memory. After exposure to misinformation, participants were unknowingly primed with associates of either the true or a suggested item. Misled participants who were primed for the true item performed better on a final memory test than did misled participants primed for neutral information. The results indicated that true and suggested information coexist and that retrieval is influenced by each concept's activation level at test. Implications for theories of the misinformation effect were discussed.