Please use this identifier to cite or link to this item: http://hdl.handle.net/1843/NCFA-836GZ7
Type: Tese de Doutorado
Title: Estudo de parâmetros potencialmente trombogênicos em usuárias de terapia hormonal (TH)
Authors: Daniela Amorim Melgaco Guimaraes do Bem
First Advisor: Ana Paula Salles Moura Fernandes
First Referee: Angélica Alves Lima
Second Referee: Ana Paula Brum Miranda Lopes
Third Referee: Alessandro Clyton de Souza Ferreira
metadata.dc.contributor.referee4: Marinez de Oliveira Sousa
metadata.dc.contributor.referee5: Henrique Pimenta Barroso Magalhaes
Abstract: A ativacao da cascata da coagulacao e fibrinolise, o grupo sanguineo ABO, o polimorfismo -675 4G/5G no gene do inibidor do ativador do plasminogenio-1 (PAI- 1), bem como o perfil lipidico e apolipoproteico foram investigados em mulheres usuarias de terapia hormonal (TH) oral (n=61) e no grupo controle (n=101). Na avaliacao dos marcadores de hipercoagulabilidade foi observado aumento significativo nos niveis de D-Di (335,67 ± 132,68 vs 527,15 ± 420,51) e FVIII (100,22± 29,25 vs 112,73 ± 35,42), e diminuicao dos niveis de PAI-1 (38,47 ± 22,61 vs 29,57 ± 16,89) em usuarias de TH oral. A frequencia dos grupos sanguineos entre controles e usuarias de TH nao apresentou diferenca significativa. Neste estudo, as mulheres pertencentes aos grupos sanguineos nao-O comparadas as mulheres grupo O, apresentaram aumento significativo de FVIII e FvW, independente do usoou nao da TH (p<0,05). Mulheres pertencentes aos grupos sanguineos nao-O usuarias de TH apresentaram aumento significativo dos niveis de FVIII (p=0,023) e D-Di (p=0,003), comparadas com as mulheres controles tambem nao-O. Os niveis de PAI-1 foram significativamente menores em mulheres sob TH oral pertencentes ao grupo sanguineo O (p=0,007). As usuarias de TH oral e pertencentes aos grupossanguineos nao-O apresentaram risco 25 vezes maior de apresentar niveis de D-Di acima do valor de referencia (OR= 25,14; IC: 5,61-109,24), comparando com o grupo de nao-usuarias portadoras do tipo sanguineo O. Nao foi observada diferenca estatistica na composicao dos grupos controle e usuarias de TH em relacao a frequencia dos genotipos do polimorfismo 4G/5G. No grupo controle niveis de PAI-1significativamente mais baixos foram observados comparando os genotipos 4G/4G com 5G/5G e 4G/5G com 5G/5G, enquanto nas mulheres usuarias de TH oral nao foi observada diferenca significativa. Comparando os dois grupos em relacao ao polimorfismo 4G/5G observou-se diminuicao significativa nos niveis de PAI-1 emusuarias de TH homozigotas 4G/4G (p=0,027) e nas heterozigotas 4G/5G (p=0,018). Usuarias de TH oral apresentaram diminuicao dos niveis de colesterol total (CT) (207,08 ± 44,28 vs 192,18 ± 48,01), LDLc (130,90 ± 37,11 vs 118,53 ± 41,40), e apo B (108,04 ± 21,01 vs 101,35), alem do aumento significativo nos niveis de HDLc(45,89 ± 9,48 vs 49,55 ± 11,11) e apo A-I (179,62 ± 26,25 vs 188,72 ± 33,60). Foi observada tambem uma diminuicao significativa no indice apoB/apoA-I (0,62 ± 0,16 vs 0,56 ± 0,14). Mulheres, usuarias de TH oral por cerca de 3 meses, apresentaram tendencia a hipercoagulabilidade demonstrada por aumento nos niveis de FVIII e DDi bem como tendencia ao aumento da fibrinolise devido a reducao nos niveis dePAI-1. A TH e os efeitos do locus ABO nos niveis do FVIII e D-Di em mulheres pertencentes aos grupos sanguineos nao-O podem aumentar o risco de apresentar niveis de D-Di acima dos valores de referencia, sugerindo efeito sinergico entre grupos sanguineos nao-O e TRH sobre a ativacao da cascata da coagulacao. Considerando o grupo sanguineo ABO e o polimorfismo 4G/5G como variaveis importantes, estudos adicionais devem ser realizados em mulheres na posmenopausaem uso de TH com o objetivo de avaliar o significado clinico dasalteracoes nos marcadores de hipercoagulabilidade e o risco de trombose.
Abstract: The activation of the coagulation and fibrinolysis, the ABO blood group, the -675 4G/5G polymorphism in the gene of the inhibitor of plasminogen activator-1 (PAI-1) and the lipidic and apolipoproteic profiles were studied in women using oral hormone therapy (HT) (n= 61) and in control group (n= 101). In the assessment of hypercoagulability markers, a significant increase in levels of D-Di (335.67 ± 132.68 vs 527.15 ± 420.51) and FVIII (100.22 ± 29.25 vs 112.73 ± 35, 42), and decreased of PAI-1 (38.47 ± 22.61 vs 29.57 ± 16.89) were observed in users of oral HT. Thefrequencies of blood groups among users of HT and controls were not significant different. Women belonging to non-O blood groups compared to the O blood group showed a significant increase in FVIII and VWF, independent of oral HT (p <0.05). Non-users of HT belonging to O blood group had a significant increase in levels of FVIII (p= 0.023) and D-Di (p= 0.003), compared with the non-O controls. The levels of PAI-1 were significantly lower in women under oral HT belonging to O blood group(p= 0.007). The users of oral HT belonging to non-O blood groups had 25 times increased risk of presenting D-Di levels above the reference value (OR = 25.14, CI: 5.61-109.24) as compared to the group of non-users carring the blood type O. There was no statistical difference in the composition of the control group and users of HT in relation to the frequency of genotypes of the 4G/5G polymorphism. In controlgroup, levels of PAI-1 were significantly lower comparing the 4G/4G genotype with 5G/5G and between 4G/5G and 5G/5G, while in the oral HT group no significant differences were observed. Comparing the two groups in relation to the 4G/5G polymorphism, a significant decrease in levels of PAI-1 in users of HT homozygous 4G/4G (p= 0.027) and 4G/5G heterozygous (p= 0.018) was observed. Users of oral HRT had decreased levels of total cholesterol (TC) (207.08 ± 44.28 vs 192.18 ±48.01), LDLc (130.90 ± 37.11 vs 118.53 ± 41.40) and apo B (108.04 ± 21.01 vs 101.35), in addition to the significant increase in levels of HDLc (45.89 ± 9.48 vs 49.55 ± 11.11) and apo A-I (179.62 ± 26.25 vs 188.72 ± 33.60). There was also a significant decrease in the ratio apoB/ApoA-I (0.62 ± 0.16 vs 0.56 ± 0.14). Women, users of oral HT for 3 months, showed a tendency to hypercoagulability demonstrated by increased levels of FVIII and D-Di as well as the increasing trend offibrinolysis due to reduction in levels of PAI-1. The HT and the effect of ABO locus on levels of FVIII and D-Di in women belonging to non-O blood groups may increase the risk for D-Di levels above the reference values, suggesting a synergistic effect of non-O blood groups and HT on activation of coagulation. Considering the ABO blood group and the 4G/5G polymorphism as important variables, additional studies mustbe conducted in post menopausal women in use of HT to evaluate the clinical significance of changes in markers of hypercoagulability and risk of thrombosis.
Subject: Sangue Circulação
Grupos sanguineos
Trombose
Hormônios
Farmácia
Sangue Coagulação
language: Português
Publisher: Universidade Federal de Minas Gerais
Publisher Initials: UFMG
Rights: Acesso Aberto
URI: http://hdl.handle.net/1843/NCFA-836GZ7
Issue Date: 29-May-2009
Appears in Collections:Teses de Doutorado

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