Effect of estrogen-progestin hormonal replacement therapy on blood coagulation and fibrinolysis in postmenopausal women

OBJECTIVE: To evaluate antithrombin III (AT), thrombin (Fragment 1+2 [F1+2] and thrombin-antithrombin [TAT]) generation markers, as well as other coagulation parameters, such as prothrombin time, partial activated thromboplastin time, thrombin time, fibrinogen, euglobulin lysis time, and platelet count, in postmenopausal women after hormonal therapy. STUDY DESIGN: Forty-five patients who received either 0.625 mg/day unopposed oral conjugated equine estrogen (CEE), 0.625 mg/day oral CEE plus medroxyprogesterone acetate (MP), or 50 µg/day transdermal 17beta-estradiol plus MP, were included. Tests were performed before (T0) and after 3 (T3), 6 (T6) and 12 (T12) months of treatment. AT was determined by an amidolytic method, whereas F1+2 and TAT complex were measured by ELISA. RESULTS: There was a significant reduction in the AT level of patients who received oral CEE plus MP at T3. There was no AT reduction in patients taking either oral CEE alone or transdermal 17beta-estradiol plus MP. F1+2 increased in all patients, but it reached statistical significance only in patients receiving transdermal 17beta-estradiol MP at T3. CONCLUSIONS: The CEE associated with MP treatment may reduce AT levels, whereas unopposed CEE or transdermal 17beta-estradiol plus MP does not change AT. These changes might not be clinically relevant in the general population; however, hormonal replacement therapy may increase the risk of thrombosis in women with congenital or acquired thrombophilia.

OBJETIVO: Avaliar os marcadores antitrombina III (AT), fragmento 1 + 2 da trombina (F1+2) e complexo trombina-antitrombina (TAT), bem como outros parâmetros da coagulação, como tempo de pró-trombina, tempo parcial de tromboplastina ativado, tempo de trombina, fibrinogênio e tempo de lise da euglobulina em mulheres na pós-menopausa após terapia hormonal. DESENHO DO ESTUDO: Foram incluídas 45 voluntárias que receberam estrogênios conjugados eqüinos (ECE) 0,625 mg/dia, isoladamente ou associado ao acetato de medroxiprogesterona (AMP) ou usaram o 17beta-estradiol (50 µg/dia) transdérmico com AMP. Os exames foram realizados antes do tratamento (T0) e após três (T3), seis (T6) e doze (T12) meses após o início do tratamento. AT foi avaliada pelo método amidolítico, enquanto que o F1+2 e o complexo TAT por ELISA. RESULTADOS: Houve redução significante nos níveis de AT em pacientes que receberam ECE associado ao AMP no T3. Não houve redução na AT em mulheres que usaram ECE isoladamente ou aquelas com 17beta-estradiol transdérmico e AMP. O F1+2 aumentou em todos os grupos, mas apenas o grupo com 17beta-estradiol transdérmico e AMP apresentou diferença significante durante o T3. CONCLUSÕES: A associação de ECE e AMP pode reduzir os níveis de AT, enquanto ECE isoladamente ou 17beta-estradiol transdérmico com AMP não modificam-o acentuadamente. Essas alterações poderiam ser mais relevantes clinicamente na análise populacional. Todavia, a terapia de reposição hormonal aumentaria o risco de trombose em mulheres com trombofilia prévia congênita ou adquirida.

Proteína C reactiva y fibrilación auricular: evidencia de un proceso inflamatorio en la iniciación y perpetuación de la arritmia / C-reactive protein and atrial fibrillation: evidence for an inflammatory process in the initiation and perpetuation of the arrhythmia

Propósitos del estudio: Determinar la existencia de un proceso inflamatorio en los pacientes (ptes) con fibrilación auricular (FA) y su eventual relación con la trombogénesis. Métodos: Se incluyeron 109 pts con valvular, tanto crónica (n =40) como paroxística (n =69) sin tratamiento anticoagulante. Se determinaron niveles de proteína C –reactiva (PCR), niveles de complejo trombina-antitrombina (TAT) y parámetros clínicos y ecocardiográficos predictores de embolia y, exámenes generales de laboratorio. Resultados: La edad promedio del grupo fue 67 ± 14 años. Los niveles de PCR fueron de 1,0 ± 1,4 mg/dl en los FA paroxística y 1,1 ± 2,4 mg/dl en los con FA crónica versus 20 controles). Los niveles de TAT confirmaron la existencia de un estado protrombótico, pero se demostró asociación entre PCR y TAT. En el análisis multivariado, la PCR se relacionó a otros marcadores de inflamación sistémica (VHS y recuento de glóbulos blancos) y la presencia de disfución VI (p =0,02). A 30 días y 1 año, se constató una caída significativa de los niveles de PCR en el grupo FA paroxística. Finalmente, los niveles de PCR resultaron ser predictores de la mantención de ritmo sinusal a 1 año (PCR =1,2 ± 1,8 mg/dl en ptes con FA versus 0,5 ± en los con ritmo sinusal a 1 año, p = 0,048). Conclusiones: Existe evidencia de un estado inflamatorio en los ptes con FA no valvular. Su persistencia se asocia a la matención de la arritmia en la evolución alejada a 1 año.

Marcadores de generacion de trombina en insuficiencia renal de niños con sindrome uremico hemolitico epidemico / Markers of thrombin generation in kidney failure of children with epidemic hemolytic uremic syndrome

Se presentan aquí los niveles de los marcadores tempranos de activación de la coagulación y del TNF-alpha en 12 niños con la forma epidémica del síndrome urémico hemolítico, de 16 meses de edad, (12-18) (mediana y rango) Todos los pacientes se recuperaron de las enfermedad dentro de las 2 a 4 semanas de evolución. Se tomaron cuatro muestras de sangre: al ingreso al hospital, luego en la primera y segunda semana y en la remisión. Las determinaciones del F1+2 TAT y TNF-alpha se realizaron por técnicas de ELISA comerciales, mientras que el factor von Willebrand se determinó por el método de Laurell. Los valores de F1+2 y del TAT al ingreso fueron 7.8 nM (3.7-12.3) y 22.7 ng/ml (8-76) respectivamente. Además, se encontró correlación significativa entre los niveles de F1+2 vs creatinina sérica, r:0.47 p < 0.001; F1+2 vs úrea sérica, r:0.66 p < 0.001; TAT vs creatinina sérica, r:0.77 p < 0.001; TAT vs urea , r:0.59 p <0.001. La mediana del FvW al ingreso en 11/12 niños fue de 260 por ciento (170-420). Los niveles del FvW se correlacionaron con los del F1+2; r:0.77 p < 0.001 y con los del TAT, r:0.41 p < 0.01. Los valores de estos marcadores séricos tendieron a normalizarse con la mejoría de la enfermedad. Se encontró una correlación negativa entre el recuento plaquetario y los niveles del F1+2, r:-0.64 p<0.001. Los niveles de TNF-alpha estuvieron aumentados en 5 niños, 22.2 pg/ml (17.2-53.7). Los resultados sugieren que estas anormalidades pueden ser atribuidas a un estímulo común sobre células endoteliales.

Thrombin-antithrombin activity and C1-inactivator in type I diabetics

Previous studies on Diabetes mellitus Type 1 ended in a controversy as to whether there was an increased or decreased fibrinolysis. Also whether fibrinolysis if present was primary or secondary to a hypercoagulable state. The results of screening tests of fibrinolysis are frequently indecisive. C[1]-Inactivator [C[1]-1] [%] as inhibitor of fibrinolysis and thrombin anti-throbmin [TA T] [ug/ml] complex as a sensitive index of the coagulation cascade were determined in 41 male patients with type I diabetes mellitus without complications and in 25 patients of the same disease with microvascular complications [retinopathy, nephropathy and/or neuropathy]. The effect of duration of the disease and the response of the disease to control, were studied. In spite of the fact that screening results of fibrinolysis were not decisive, C[1] -1 and TA T were specific and indicative. TA T was higher in complicated cases [m 9.7 +/- 2.1 SD] than in non-complicated ones [m 5.6 +/- 2.7 SD]; and in uncontrolled complicated cases [m 11.3 +/- 3.0 SD] than in controlled ones [m 9.7 +/- 2.1 SD]. The effect of control was evident also in non-complicated cases where TAT was higher in uncontrolled [m 6.2 +/- 1.9 SD] versus controlled ones [5.6 +/- 2.7 SD]. The longer the duration of the disease the higher the level of TA T, where it was [m 7.2 +/- 2.1 SD] in 1-2 yrs duration and reached m 10.2 +/- 3.1 SD in 5-9 yrs duration. C[1]-l was also higher in complicated diabetes [m 118.6. +/- 18.5 SD] than in non-complicated cases [m 107.5 +/- 16.0 SD] and in both complicated uncontrolled cases [116.3 +/- 15.0 SD] than in complicated controlled ones [118.6 +/- 18.5 SD] also in non-complicated uncontrolled cases [m 115.0 +/- 18.8 SD] than in controlled ones [m 107.5 +/- 160 SD]. The results point to an increased rate of fibrinolysis in response to increased hypercoagulable state in type I Diabetes Mellitus and this is more accentuated the longer the duration of the diseases and that both improve on a better control of the disease