Pré-eclâmpsia grave: via do fator tissular e polimorfimos no gene do fator VII

• Ano de defesa: 2012
• Autor(a) principal: Lara Carvalho Godoi
• Tipo de documento: Tese
• Tipo de acesso: Acesso aberto
• Idioma: por
• Instituição de defesa: Universidade Federal de Minas Gerais; UFMG
• Palavras-chave em Português: Pré-eclâmpsia; Fator VII ativado; polimorfismos no gene do fator VII; fator VII; inibidor da via do fator tissular; fator tissular; Farmácia
• Link de acesso: http://hdl.handle.net/1843/EMCO-93RG27

Preeclampsia (PE), in its pure form, is characterized by the onset of hypertension and proteinuria in normotensive pregnant women, after the twentieth week of pregnancy. The PE is associated with a hypercoagulable state even more evident that the physiological condition of pregnancy. The actual model accepted for the blood coagulation process detaches the tissue factor (TF) as the essential factor to trigger the coagulation cascade pathway, which leads to fibrin blood clot formation. When vascular damage occurs, blood is exposed to TF that binds to factor VII (FVII), activating it (FVIIa). The TF/FVIIa complex activates directly factors X and IX, resulting in thrombin generation and consequently in fibrinogen cleavage into fibrin monomers. The tissue factor pathway inhibitor (TFPI) is the main endogenous inhibitor, in vivo, of the TF pathway. Previous studies suggested a relation between FVII gene polymorphisms, -402GA and -401GT, and its plasma levels. The aim of this study was to evaluate TF, TFPI, FVII and FVIIa plasma levels, the FVII gene polymorphisms and the occurrence of severe PE. A group of 335 women were evaluated, of whom 109 were pregnant with severe PE (group I), 106 normotensive pregnant women (group II) and 120 nonpregnant women (group III). The comparison of the TF levels did not show any difference among the three groups (333,91; 290,13 e 392,95 pg/mL para os grupos I, II e III respectively). The TFPI (83,48; 56,09 e 46,29 ng/mL para os grupos I, II e II respectively), FVII (521,88; 294,63 e 134,85 ng/mL para os grupos I, II e II respectively) e FVIIa (88,68; 67,78 e 45,28 mU/mL para os grupos I, II e II respectively) plasma levels were significantly higher in group I when compared to group II (p<0,001; 0,001 and 0,014, respectively) and III (p<0,001, in all cases). The comparison between groups I and II, grouping by the pregnancy age, showed an increase of TFPI and FVII in group I, when compared to group II, in all ranges of pregnancy age evaluated. FVIIa did not show difference in this comparison. The correlation between the groups I x II, I x III and II x III by evaluating the ROC curve, showed that TFPI, FVII and FVIIa are able to distinguish pregnant with severe PE or normotensive pregnant from nonpregnant women, but they are not able to distinguish pregnant with severe preeclampsia from normotensive pregnant. The genotypic frequency of the polymorphisms -401G/T and -402G/A did not show differences when comparing the three groups. The polymorphisms evaluated are not associated with changes in FVII plasma levels in pregnant women with severe PE. The allele -401T was more frequent in the group with severe PE and was associated with the decrease of FVII plasma levels when the women were evaluated together