title: Defining severity of hemophilia: more than factor levels.
abstract: Patients with severe hemophilia generally exhibit a severe bleeding phenotype with bleeding into joints or muscles at an early age. Although the severity and frequency of bleeding symptoms correlate with the residual factor VIII/IX (FVIII/IX) activity in the plasma, a considerable variability in bleeding pattern, FVIII/IX concentrate utilization, and joint damage has been observed. A subset of 10 to 15% of patients with severe hemophilia A shows a milder disease phenotype with significantly reduced frequencies of spontaneous bleeding and lower requirements for factor concentrate. This mitigated clinical phenotype is determined by the underlying mutations in the F8/F9 genes, genetic alterations and polymorphisms in other genes of the hemostasis system, differences in inflammatory and immune response genes, limitations in laboratory diagnostics, as well as environmental factors. Identification of disease-modifying factors in hemophilia may influence treatment decisions, such as starting and tailoring prophylaxis according to the specific clinical phenotype, rather than just the laboratory-defined degree of severity. This review focuses on the current information of factors mitigating the clinical presentation of hemophilia and contributing to its high phenotypic heterogeneity.
authors.affiliation: Department of Molecular Haemostaseology, Institute of Experimental Haematology and Transfusion Medicine, University Clinic Bonn, Bonn, Germany.
authors.forename: Anna
authors.initials: A
authors.lastname: Pavlova
authors.forename: Johannes
authors.initials: J
authors.lastname: Oldenburg
mesh_terms: D005164:Factor IX / Q000235:genetics / Q000378:metabolism; D005169:Factor VIII / Q000235:genetics / Q000378:metabolism; D006467:Hemophilia A / Q000097:blood* / Q000235:genetics / Q000473:pathology*; D002836:Hemophilia B / Q000097:blood* / Q000235:genetics / Q000473:pathology*; D006801:Humans; D012720:Severity of Illness Index
chemical_list: D005169:Factor VIII; D005164:Factor IX