title: Haemostatic patterns and bleeding scores of a genetically characterised Italian family with combined haemophilia A and type 1 von Willebrand disease.
abstract: : We report on the coinheritance of mild haemophilia A and type 1 von Willebrand disease (VWD) in a genetically characterized Italian family. The proband is a 56-year-old man carrying both the c.2167G>A mutation in the factor VIII (FVIII) gene (responsible for p.A723T substitution) and the c.4751A>G mutation (p.Y1584C) in the von Willebrand factor (VWF) gene. His FVIII and VWF levels were 9.8 and 43.2 IU/dl, respectively. His bleeding symptoms included mucocutaneous bleeding, haemarthrosis, and muscle haematomas. Using the bleeding assessment tool, a questionnaire currently employed in diagnosing VWD, the patient had a bleeding score of 27 as compared with the 10.2 ± 3.4 found in patients with mild-to-moderate haemophilia A, and 0-3 in normal men. One of the proband's two daughters (both obligate carriers of haemophilia A) also harboured the VWF p.Y1584C mutation. Her FVIII and VWF levels were 45.9 and 54 IU/dl, respectively, and her bleeding score was slightly higher than normal for women (6 vs. 0-5). The other daughter had a normal bleeding score, and so did the proband's father (with type 1 VWD) and mother (haemophilia A carrier). Discrepancies between haemostatic patterns and bleeding symptoms in cases of haemophilia A, as seen in our patient, suggest the need to search for other coagulation defects, especially involving VWF, which is the carrier of FVIII. Although the presence of a VWF mutation significantly exacerbates the haemorrhagic complications in patients with mild haemophilia A, it has only mild effects on haemophilia A carriers.
authors.affiliation: aDepartment of Cardiologic, Thoracic and Vascular Sciences bDepartment of Medicine, Thrombohaemorrhagic Disorders Unit, University of Padua Medical School, Padua, Italy.
authors.forename: Viviana
authors.initials: V
authors.lastname: Daidone
authors.forename: Elena
authors.initials: E
authors.lastname: Pontara
authors.forename: Francesca
authors.initials: F
authors.lastname: Boscaro
authors.forename: Maria G
authors.initials: MG
authors.lastname: Cattini
authors.forename: Marta
authors.initials: M
authors.lastname: Milan
authors.forename: Alessandra
authors.initials: A
authors.lastname: Casonato
mesh_terms: D000328:Adult; D000369:Aged, 80 and over; D005260:Female; D006467:Hemophilia A / Q000188:drug therapy* / Q000235:genetics; D006487:Hemostasis / Q000502:physiology*; D006490:Hemostatics / Q000378:metabolism*; D006801:Humans; D007558:Italy; D008297:Male; D008875:Middle Aged; D055815:Young Adult; D056725:von Willebrand Disease, Type 1 / Q000188:drug therapy* / Q000235:genetics
chemical_list: D006490:Hemostatics