Assuntos
Homocisteína/sangue , Oxirredutases atuantes sobre Doadores de Grupo CH-NH/genética , Complexo Vitamínico B/sangue , Análise de Variância , Ácido Fólico/sangue , Genótipo , Humanos , Indígenas Sul-Americanos/genética , Metilenotetra-Hidrofolato Redutase (NADPH2) , Oxirredutases atuantes sobre Doadores de Grupo CH-NH/sangue , Polimorfismo Genético , Venezuela/etnologia , Vitamina B 12/sangueRESUMO
The Activated Protein C Resistance (APCR) is the common phenotype of Factor V Leiden (arg506gln), which is considered as a thrombotic risk factor. The aim of this study was to determine the prevalence of APCR and its association with Factor V Leiden in indian and black populations from Zulia State in western Venezuela. Blood samples were taken from 80 Yukpa indians from Sierra de Perijá and 91 black individuals from the southeast of Lago de Maracaibo. APCR was determined by the Dahlback's method with the modifications of Jorquera et al. and Trossaert et al. The results were expressed as n-APC-SR (positive value < or = 0.75). Factor V Leiden genotype was identified by PCR and restriction analysis standard methods at the Institute of Human Genetics (Greifswald, Germany). No significative difference was found between n-APC-SR from indians (mean +/- SEM 1.13 +/- 0.02, CI 95% = 1.07-1.19) and black people (1.07 +/- 0.02, CI 95% = 1.03-1.12). APCR prevalence from indians was 1.25% (1 out of 80) who was heterozygote case for F V Leiden and 4.4% (4 out of 91) from blacks (one case was heterozygous for F V Leiden). No thrombotic event personal or familial was demonstrate. Our data represent the first report related to the association between APCR and F V Leiden in venezuelan indian and black individuals. APCR without the Factor V Leiden expression suggest a different type of mutation in the Factor V molecule. In spite of high endogamy in the indian group, we can not discard the role of foreign genes in both populations. The determination of the prevalence of this phenotype and its molecular marker in various ethnic groups is important for the interpretation of their role as risk factors for thrombotic disease.
Assuntos
Resistência à Proteína C Ativada/genética , População Negra/genética , Indígenas Sul-Americanos/genética , Resistência à Proteína C Ativada/epidemiologia , Fator V/genética , Humanos , Mutação , Fenótipo , Prevalência , Trombose/epidemiologia , Trombose/genética , Venezuela/epidemiologiaRESUMO
Some previous reports indicated that a minimal amount of anti-IIa is necessary for the optimal anti-Xa activity of low molecular weight heparin (LMW-H). To know if we could improve the prophylactic activity of LMW-H, providing a mild antithrombin effect, we conducted an experiment in which we administered subcutaneously to 10 volunteers, very low doses of unfractionated heparin (UFH), (1000 IU), a LMW-H (enoxaparin, 2000 IU = 20mg), or both heparins together on alternate days, and measure the anti-Xa activity before, and 4 hours after injection. We found that the anti-Xa activity in the first group (UFH), increased by 33%, over the basal values; in the second group (LMW-H), by 93%, but it increased by 282%, in the third group (UFH + LMW-H) showing clearly (p < 0.0069), that UFH could increase synergistically, more than additive, the anti-Xa activity of enoxaparin. The impact on the cost-effectiveness of antithrombotic prophylaxis and the therapeutic results with the herein combined scheme should be evaluated.
Assuntos
Anticoagulantes/farmacologia , Inibidores do Fator Xa , Heparina de Baixo Peso Molecular/farmacologia , Heparina/farmacologia , Sinergismo Farmacológico , HumanosRESUMO
Resistance to activated protein C (APC) is the most common inherited risk factor for venous thrombosis. Most cases of APC resistance are caused by the point mutation nt 1691 G-A in factor V gene, referred to as factor V Leiden mutation. As initially shown in a Dutch population, this mutation has a carrier rate of 2.9%, the most frequent genetic disposition for thrombophilia and deep venous thrombosis. By large-scale epidemiological studies we have determined the prevalence of factor V Leiden mutation in populations from Poland (200), Argentina (215), Venezuela (126), Costa Rica (196), and India (150). The prevalences have been estimated for Poland (Warsaw) 5.0%, Argentina (Buenos Aires) 5.1%, Venezuela (Valencia) 1.6%, Costa Rica (San José) 2.0%, and India (Punjab) 1.3%. Based on worldwide distribution, it can be hypothesized that the factor V Leiden mutation has originated and accumulated in central European Caucasians and spread over the world by migration.
Assuntos
Fator V/genética , Genética Populacional , Mutação Puntual , Tromboflebite/etnologia , Tromboflebite/genética , População Branca , Argentina/epidemiologia , Costa Rica/epidemiologia , Feminino , Frequência do Gene , Testes Genéticos , Alemanha/epidemiologia , Heterozigoto , Humanos , Índia/epidemiologia , Recém-Nascido , Masculino , Mutação , Polônia/epidemiologia , Prevalência , Distribuição Aleatória , Distribuição por Sexo , Venezuela/epidemiologiaRESUMO
A patient with transient microhaematuria was studied. Coagulation tests revealed prolonged thrombin and reptilase times concomitant with abnormal fibrin polymerization rate (also abnormal in both parents). In the patient and her patients, the abnormal fibrin polymerization rate was only slightly corrected by addition of calcium ions. The alpha-chain had a molecular weight higher than normal and there was deficient formation of alpha-polymers. The molecule showed a more anodal migration than the control. The abnormality described has been classified as Fibrinogen Lima.
Assuntos
Afibrinogenemia/genética , Fibrinogênios Anormais/isolamento & purificação , Hematúria/etiologia , Afibrinogenemia/sangue , Afibrinogenemia/complicações , Eletroforese das Proteínas Sanguíneas , Cálcio/farmacologia , Criança , Consanguinidade , Feminino , Fibrinogênio/genética , Fibrinogênios Anormais/genética , Fibrinogênios Anormais/metabolismo , Humanos , Fragmentos de Peptídeos/genética , Polímeros , Tempo de TrombinaRESUMO
Dipyridamole has been reported to inhibit platelet aggregation in citrate anticoagulated whole blood (WB). However, citrate may alter the response of platelets and/or the effect of antiplatelet drugs. The present study evaluates the "ex vivo" effect of dipyridamole, two hours after a single dose (3 mg/Kg) in 25 normal subjects in non-anticoagulated (native) WB and in WB anticoagulated with citrate or hirudin. We have used the BASIC anticoagulated with citrate or hirudin. We have used the BASIC wave as analytical method, which can evaluate the early steps of platelet activation with collagen in less than 1 min after venoclysis, thus allowing the study in native WB. The results show that dipyridamole significantly inhibits (p less than 0.001) platelet activation to collagen in citrated WB (66%) while the drug's effect is much lower (21%) and non-significant if evaluated in native or hirudine anticoagulated WB. These results suggest that citrate or low calcium concentration amplify the drug's platelet inhibitory action in WB and, therefore, the laboratory results may overestimate the drug's effect "in vivo".