title: The impact of prothrombotic mutations on factor consumption in adult patients with severe hemophilia.
abstract: About 10% of patients with severe hemophilia exhibit a milder clinical phenotype with less frequent bleeds. Among many other factors, coinheritance of prothrombotic mutations have been proposed to act as modulators of clinical severity in severe hemophilia. We conducted a study to evaluate the impact of 3 prothrombotic mutations (factor V Leiden, factor II, and methylenetetrahydrofolate reductase mutations) on clinical phenotype of patients with severe hemophilia in our institution. For this purpose we compared the average annual factor concentrate consumption between carriers and noncarriers of prothrombotic mutations. A total of 38 hemophilia A and B patients with factor levels less than 1 were recruited between October 2006 and October 2007. Prothrombotic mutations were detected in venous blood using polymerase chain reaction amplification technique. Eighteen patients (47%) carried no prothrombotic mutations. The remaining 20 patients (53%) were found to be carriers of either 1 or 2 mutations. Median age in both carrier and the non-carrier groups was 27 years. None of the patients in either group gave a history of thromboembolic event. Median annual factor concentrate consumptions in carriers and noncarriers were 610 +/- 530 units/kg and 770 +/- 670 units/kg, respectively (P = .203). Our results demonstrated no significant difference in annual factor concentrate consumption between carriers and noncarriers of prothrombotic mutations. Considering that average annual factor consumption is a surrogate indicator of clinical phenotype, we concluded that coinheritance of prothrombotic mutations was not associated with occurrence of different clinical phenotypes in severe hemophilia.
authors.affiliation: Department of Internal Medicine, Division of Haematology, Cerrahpasa Medical Faculty, Istanbul University, Istanbul, Turkey. muhcar@superonline.com
authors.forename: M Cem
authors.initials: MC
authors.lastname: Ar
authors.forename: Onur
authors.initials: O
authors.lastname: Baykara
authors.forename: Ayse Nur
authors.initials: AN
authors.lastname: Buyru
authors.forename: Zafer
authors.initials: Z
authors.lastname: Baslar
mesh_terms: D000293:Adolescent; D000328:Adult; D016022:Case-Control Studies; D005165:Factor V; D005169:Factor VIII / Q000627:therapeutic use*; D020022:Genetic Predisposition to Disease; D006467:Hemophilia A / Q000188:drug therapy* / Q000235:genetics*; D002836:Hemophilia B; D006801:Humans; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics; D009154:Mutation; D010641:Phenotype; D016133:Polymerase Chain Reaction; D011516:Prothrombin / Q000235:genetics; D019851:Thrombophilia / Q000235:genetics*; D055815:Young Adult
chemical_list: C095381:factor V Leiden; D005165:Factor V; D011516:Prothrombin; D005169:Factor VIII; D042965:Methylenetetrahydrofolate Reductase (NADPH2)