RESUMO
Thrombophilia is a complex hypercoagulable state that increases the risk of thrombosis. Most reports in medical literature of the Mexican population with this disease lack statistical validity. Therefore, the aim of this study is to describe the prevalence of primary thrombophilia in a tertiary referral hospital in Mexico. This is a study of patients referred to our hospital because of a hypercoagulable state and who later on were diagnosed with primary thrombophilia. The thrombophilia workup included methylenetetrahydrofolate reductase (MTHFR) C677T, antiphospholipid antibodies, protein C, protein S, antithrombin, factor VIII, factor V Leiden, prothrombin mutation G20210A, activated protein C resistance, JAK2 V617F and homocysteine. Ninety-five individuals were tested. The MTHFR C677T polymorphism was the most frequent anomaly in 84.1% of the tested individuals. There was a relatively low prevalence of factor V Leiden (5.2%) and anticoagulant protein deficiency (8.3%). The MTHFR C677T polymorphism has a very high prevalence compared with the low prevalence of anticoagulant protein deficiency and factor V Leiden mutation in Mexicans.
Assuntos
Trombofilia/etnologia , Trombose/etnologia , Adolescente , Adulto , Idoso , Feminino , Humanos , Masculino , México , Pessoa de Meia-Idade , Estudos Retrospectivos , Centros de Atenção Terciária , Trombofilia/genética , Trombose/genética , Adulto JovemRESUMO
Warfarin is the most prescribed oral anticoagulant worldwide. Because of the complexity of warfarin therapy, we attempted to dissect genetic from bioenvironmental factors influencing warfarin dose responses in individuals of a genetic isolate of Hispanic ancestry. A total of 191 patients with standard values of international normalized ratio were recruited. Three groups with a significantly different warfarin dose response were identified, that is, sensitive (2.28 +/- 0.50 mg/d), intermediate (4.2 +/- 0.76 mg/d), and resistant (7.40 +/- 1.54 mg/d; Tukey test, P < .001). Age had a significant inverse correlation with warfarin dose (P < .001; effective dose diminished 0.56 mg/d/decade). Required doses were higher for individuals with CYP2C9 variants containing the allele *1 compared to those individuals with variants composed of other alleles (P = .006). Similarly, individuals with VKORC1-1639GG and VKORC1-1639GA genotypes also required higher doses compared to the AA genotype (P < .001). Evaluation of potential gene-gene interactions between CYP2C9 and VKORC1 polymorphisms showed significant differences in dosing for CYP2C9 genotypes within the VKORC1-1639G/A subgroup (P = .013). A stepwise multivariate linear regression analysis showed that 38.2% of the warfarin dose response variance was accounted for by a model involving age (20.9%), VKORC1-1639G/A (11.3%), and CYP2C9*1, *2, and *3 variants (7.1%). These results corroborate previous findings on warfarin pharmacogenetics and define a contrastable gene-bioenvironment interaction model suited to be used in Hispanic populations.
Assuntos
Anticoagulantes/administração & dosagem , Hidrocarboneto de Aril Hidroxilases/genética , Oxigenases de Função Mista/genética , Trombose , Varfarina/administração & dosagem , Adulto , Idoso , Anticoagulantes/farmacocinética , Colômbia/epidemiologia , Citocromo P-450 CYP2C9 , Relação Dose-Resposta a Droga , Etnicidade/estatística & dados numéricos , Feminino , Frequência do Gene , Variação Genética , Genótipo , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Trombose/etnologia , Trombose/genética , Trombose/prevenção & controle , Vitamina K Epóxido Redutases , Varfarina/farmacocinéticaRESUMO
Individuals belonging to six different Amerindian tribes and two African groups of Costa Rica were genotyped for factor V Leiden (FV), factor V haplotype HR2 (FV HR2), Factor II 20210G>A (FII), the methylenetetrahydrofolate reductase (MTHFR), factor VII polymorphisms (FVII IVS7, FVII R353Q), factor XIII (FXIII V34L), and the insertion/deletion (I/D) polymorphism of the gene of angiotensin converting enzyme (ACE). Clear differences in the prevalence were found and are first reported. The prevalence of some of the established genetic risk factors was low in Amerindians of Costa Rica (ACE) or even absent (FVL, FII), and others (MTHFR, FVHR2) had an extremely high prevalence. People of African origin carried very rare FVL or FII polymorphisms, but the DD genotype of ACE is the highest reported. Concerning the protective factors, the QQ genotype of FVII R353Q was absent in Amerindians, but the protective 7/7 genotype of FVII IVS7 frequently found. Novel alleles of FVII IVS7 (4, 8, and 9 monomers) were found. Intertribal heterogeneity was observed that may reflect the evolutionary history of these tribal groups and their admixture with other populations.
Assuntos
População Negra/genética , Indígenas Centro-Americanos/genética , Trombose/genética , Acetilcolinesterase/genética , Alelos , Costa Rica/epidemiologia , Frequência do Gene , Marcadores Genéticos/fisiologia , Humanos , Polimorfismo Genético , Prevalência , Fatores de Risco , Trombose/etnologiaRESUMO
A group of 102 Mexican Mestizo patients with appropriate clinical features suggestive of primary thrombophilia was prospectively studied. Thirty-nine percent of them had activated protein C resistance, but only four patients displayed the factor V Leiden mutation. Five percent of the individuals were found to be protein C deficient, whereas 2% had protein S deficiency. No cases of abnormalities in antithrombin III, plasminogen, tissue-type plasminogen activator or plasminogen activator inhibitor were found. The low prevalence of the activated protein C resistance genotype, probably stemming from the genetic admixture of the Mexican Mestizo group is noteworthy.
Assuntos
Trombose/epidemiologia , População Branca/genética , Resistência à Proteína C Ativada/epidemiologia , Resistência à Proteína C Ativada/etnologia , Resistência à Proteína C Ativada/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Humanos , Indígenas Norte-Americanos/genética , México/epidemiologia , Pessoa de Meia-Idade , Fenótipo , Prevalência , Estudos Prospectivos , Deficiência de Proteína C/epidemiologia , Deficiência de Proteína C/etnologia , Deficiência de Proteína S/epidemiologia , Deficiência de Proteína S/etnologia , Trombose/etnologia , Trombose/genéticaRESUMO
Se estudia la historia clínica de una paciente de sexo femenino y 64 años de edad, quien fue internada en el Hospital Sano Tomás con diagnóstico de Diabetes Mellitus y acidosis severa y por una úlcera necrótica en el paladar blando. La paciente desarrolló durante su hospitalización un cuadro clínico compatible con trombosis del seno cavernoso. La biopsia y la necropsia confirmaron que tenía mucormicosis palatina, una complicación fatal en el paciente diabético y pobremente controlado