Prevalence of Factor V Leiden in a healthy population in Santa Catarina, Southern Brazil.

Thrombophilic disorders are found in 50% of patients with venous thromboembolism, and factor V Leiden (FVL) is the most common genetic risk factor for the development of these conditions. FVL prevalence varies according to population group. In Europe, many countries have a high prevalence of the mutation, including Portugal, Germany, and Italy. Santa Catarina State, southern Brazil, was colonized by different European nations; most inhabitants are descendants of Portuguese, Italian, and German immigrants. There are, however, no data on the prevalence of FVL in the state. This study aimed to determine FVL prevalence in a healthy population in Santa Catarina and assess whether there is an association between the mutation and demographic characteristics, thereby contributing to the understanding of the heterogeneity of prevalence of this important VTE risk factor and racial or geographical differences in the incidence of thrombotic diseases. Analysis of the FVL mutation was performed on 400 blood donors using the PCR technique followed by enzymatic digestion. The findings show that 2.5% of the participants were heterozygous for FVL, and none were homozygous. No association was found between the presence of FVL in heterozygosis and individual characteristics. In conclusion, this study found a prevalence of FVL in heterozygosis of 2.5% among healthy individuals in Santa Catarina, Brazil. Further studies are needed to assess the prevalence of FVL in other regions of the country, determine the distribution of the mutation among population groups, and evaluate how these factors affect the incidence of thrombotic diseases.

Resistencia a la proteína C activada: estudio de laboratorio y prevalencia del defecto en la población chilena / Activated protein C resistance: laboratory study and prevalence of the defect in 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 percent and around 20 percent 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 predict 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 Mnll enzyme digestion of PCR amplified genomic fragment containing the nucleotide 1.691. The lower limit of APTT ratio stablished in this group was 2.13. APCR was found in 6 out of 159 control subjects (3.8 percent) and in 14/50 (28 percent) of patients with thrombosis. In 13 cases as a single defect and in 1 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 preventive therapy at risk situations

[Activated protein C resistance as a cause of thrombophilia]. / Resistencia a la proteína C activada como causa de trombofilia.

The proportion of identifiable causes of familial thrombophilia has increased from 5-10% to 60-70% since the identification of activated protein C resistance (aPCR) in February 1993 by Dahlbäck et al. A mutation in the factor V gene (G-->A, 1691) leads to the so called Leiden mutation (R 506 Q) that produces a mutated factor V resistant to the catalytic action of activated protein C (aPC), yet normal in its procoagulant properties. This recently identified aPCR is in Nordic populations the most prevalent and well defined genetic defect associated with disease so far described. Its prevalence in the general population ranges from 0% to up to 15% and suggests that a positive genetic selection pressure has been involved. The aPCR phenotype can be assessed in vitro by measurement of the prolongation of the activated partial thromboplastin time in the presence of aPC, whereas the aPCR genotype is studied using polymerase chain reaction searching for the Arg to Gln mutation in the coagulation factor V gene. Some acquired conditions such as the presence of lupus anticoagulants, antiphospholipid antibodies, pregnancy, liver disease and contraceptives may lead into the aPCR phenotype. The aPCR search must be the initial step in the study of a patient with thrombophilia, either inherited or acquired aPCR together with protein C, protein S and antithrombin III explain 60 to 70% of cases of familial thrombophilia.