title: Activated protein c resistance (APC) and inherited factor V (FV) mis-sense mutation in patients with venous and arterial thrombosis in a haematology clinic.
abstract: BACKGROUND
  Inherited factor V (FV) mis-sense point mutation has recently been identified as a major cause of familial venous thrombosis. The incidence of this congenital haemostatic disorder in Australia is unknown.
  
  
  OBJECTIVE
  To examine the incidence of this congenital defect in patients with thrombosis attending a haematology clinic.
  
  
  METHODS
  Individuals investigated or treated for venous and arterial thrombosis over a four month period, as well as those who were on anticoagulant for valvular replacement or arrhythmia were studied for the presence of FV mis-sense point mutation, FV Q506 (G to A at nucleotide position 1691) by a polymerase chain reaction based test, and activated protein C (APC) resistance using an APTT based coagulation assay.
  
  
  RESULTS
  Forty-five patients with venous thromboembolism (VTE), 20 patients with coronary artery disease and 25 patients with valvular replacement or arrhythmia who were on anticoagulant were examined. The frequency of FV mis-sense point mutation in these three groups was 26.7%, 15% and 4% respectively. In this study, patients with FV Q506 were of a younger age and had a higher incidence of extensive thrombosis or recurrence as compared to those with the normal factor V gene. This mutation was found in a diverse group of people (four of the 12 patients were of non-European origin). Nearly 50% of these patients had other risk factors for VTE. The number of patients with a family history of VTE was similar for those with the FV mutation and the normal FV.
  
  
  CONCLUSIONS
  This study confirms the high incidence of FV Q506 mutation in patients with VTE reported overseas. Several clinical features, i.e. young age of onset of VTE, high recurrence rate, diverse ethnic background and importance of associated risk factors are highlighted. The findings in this study also raise the possibility that this mutation may be a risk factor for arterial thrombosis. Large studies are required to substantiate these findings.
authors.affiliation: Haematology Department, Royal North Shore Hospital, Sydney, NSW.
authors.forename: D D
authors.initials: DD
authors.lastname: Ma
authors.forename: M R
authors.initials: MR
authors.lastname: Aboud
authors.forename: B G
authors.initials: BG
authors.lastname: Williams
authors.forename: J P
authors.initials: JP
authors.lastname: Isbister
mesh_terms: D000328:Adult; D017677:Age Distribution; D000368:Aged; D000369:Aged, 80 and over; D001315:Australia; D003327:Coronary Disease / Q000208:ethnology / Q000235:genetics; D004351:Drug Resistance / Q000235:genetics; D005060:Europe / Q000208:ethnology; D005165:Factor V / Q000235:genetics*; D005260:Female; D006487:Hemostasis / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D008877:Middle East / Q000208:ethnology; D017354:Point Mutation; D011486:Protein C / Q000235:genetics*; D012008:Recurrence; D012307:Risk Factors; D013924:Thrombophlebitis / Q000097:blood / Q000208:ethnology / Q000235:genetics* / Q000503:physiopathology; D013927:Thrombosis / Q000097:blood / Q000208:ethnology / Q000235:genetics* / Q000503:physiopathology
chemical_list: D011486:Protein C; D005165:Factor V