[Activated C protein resistance: laboratory study and prevalence of the defect in the Chilean population].
Activated protein C resistance (APCR) or Factor V Leiden has been recently described as the most prevalent hemostatic abnormality associated with venous thrombosis. In patients with familial thrombophilia, the prevalence of APCR is 19-60% and around 20% in sporadic venous thrombosis. APCR is usually measured by the degree of prolongation of Activated Partial Thromboplastin Time (APTT) on patient's plasma, induced by addition of APC in comparison to normal plasma. At the molecular level the defect is caused by a single-point mutation in the gene for factor V (FV) (G1.691-->A), that predicts the replacement of Arg506 by Glutamine. This mutation makes activated factor V resistant to inactivation by APC. Since the prevalence of the defect is highly variable among different populations, the objective of this work was to study its frequency in our population and in patients with thrombophilia. We defined the normal range for APTT ratio (APTT + APC/APTT - APC) in a group of 73 healthy volunteers in whom the presence of FV Q506 mutation was searched using Mull enzyme digestion of PCR amplified genomic fragment containing the nucleotide 1.691. The lower limit of APTT ratio established in this group was 2.13. APCR was found in 6 out of 159 control subjects (3.8%) and in 14/50 (28%) of patients with thrombosis. In 13 cases as a single defect and in one associated to type I protein C deficiency. All the APCR patients and control subjects were heterozygotes by gene analysis. The results demonstrate that in our population APCR is also the most common defect associated with thrombosis, in accordance with a high prevalence in the population. The ability to screen for this defect will permit the identification of carriers that would benefit of preventive therapy at risk situations.
Pereira
J
J
Departamento de Hematología-Oncología, Escuela de Medicina, P Universidad Católica de Chile, Santiago de Chile.
Quiroga
T
T
Goycoolea
M
M
Muñoz
B
B
Hidalgo
P
P
Kaltwasser
G
G
Mezzano
D
D
D001483:Base Sequence; D002677:Chile; D004198:Disease Susceptibility; D005165:Factor V / Q000235:genetics*; D005166:Factor V Deficiency / Q000235:genetics; D006801:Humans; D008969:Molecular Sequence Data; D010314:Partial Thromboplastin Time; D017354:Point Mutation; D016133:Polymerase Chain Reaction; D011486:Protein C / Q000502:physiology*
D011486:Protein C; D005165:Factor V
Resistencia a la proteina C activada: estudio de laboratorio y prevalencia del defecto en la población chilena.