Trombosis Venosa

Trombosis venosa en el síndrome nefrótico

Kauffman y colleagues dijeron que el estado trombofilico del síndrome nefrótico es una consecuencia de una perdida de endógeno anticoagulante antitrombina III en la orina como resultado de la alteración permeoselectiva de la membrana basal glomerular.

Se han identificado varios mecanismos que promueven la trombosis en pacientes con nefrosis, estos mecanismos se dividen en dos categorías: perdida urinaria de proteínas que previene la trombosis y mayor síntesis de factores que promueven la trombosis. En la prevención de la trombosis un 40 a un 80 % de los pacientes con síndrome nefrótico se encontraron que se han reducido los niveles circulantes de la antitrombina III, debido a la perdida urinaria de la actividad de la proteína C anticoagulante y los niveles de proteína S también parecen reducirse en pacientes con el síndrome nefrótico.

La activación de la coagulación en pacientes con síndrome nefrótico es acompañada por el aumento en los niveles de factores V y VIII factor de von Wilebrand, fibrinógeno y alfa 2 megroblobulina, el aumento de fibrinógeno promueve la agregación plaquetaria, proporciona el sustrato para la formación de fibrina, aumenta la viscosidad de la sangre y promueve el eritrocito, la hiperreactividad trombocitosis y plaquetas también acompañan el síndrome nefrótico. La hipoalbuminemia conduce a mayor biodisponibilidad del ácido araquidónico liberado por las plaquetas, mejorar el reclutamiento de otras plaquetas.

Hipercolesterolemia aumenta la sensibilidad agonista dependiente de las plaquetas, promoviendo su activación, terapia y reductores del colesterol con estatinas reduce la agregación plaquetaria y disminuye el riesgo de trombosis venosa en pacientes con nefrosis.

http://www.nejm.org/doi/full/10.1056/NEJMcibr1209459

Venous Thrombosis in the Nephrotic Syndrome

Joseph Loscalzo, M.D., Ph.D.

N Engl J Med 2013; 368:956-958March 7, 2013DOI: 10.1056/NEJMcibr1209459

The Clinical Implications of Basic Research series has focused on highlighting laboratory research that could lead to advances in clinical therapeutics. However, the path between the laboratory and the bedside runs both ways: clinical observations often pose new questions for laboratory investigations that then lead back to the clinic. One of a series of occasional articles drawing attention to the bedside-to-bench flow of information is presented here, under the Basic Implications of Clinical Observations rubric. We hope our readers will enjoy these stories of discovery, and we invite them to submit their own examples of clinical findings that have led to insights in basic science.

Thrombotic events complicate the nephrotic syndrome in approximately 25% of patients.1 This association was first recognized in the 19th century by W. Howship Dickinson, who pointed out that “when the kidneys themselves are the seat of chronic disease, involving the loss of albumin, . . . the blood in their vessels, as elsewhere, is rendered morbidly coagulable by the drain.”2 This observation was refined with the association between a specific renal condition (the nephrotic syndrome) and venous thrombosis, as reported by Derow and colleagues in 1939.3

Although there was considerable debate as to what was cause and what was effect, we now view the nephrotic syndrome as a thrombophilic or hypercoagulable state.4 This conclusion was based on the demonstration of elevated plasma levels of fibrinogen and other clotting factors, accelerated generation of thromboplastin, and thrombocytosis in 35 untreated patients with nephrosis who did not have either azotemia or clinical thrombosis. Soon thereafter, Kauffmann and colleagues5 suggested that the thrombophilic state of the nephrotic syndrome is a consequence of a loss of endogenous anticoagulant antithrombin III in the urine as a result of altered permselectivity of the glomerular basement membrane. The concept of size-selective permeability of the glomerular basement membrane was first proposed in 1967 with the use of an animal model of immune-mediated nephrotic syndrome.6 After that initial study, several studies addressed the determinants of molecular exclusion according to size and charge and their modification in nephrosis,7,8

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