PLAQUETAS Y ENFERMEDAD TROMBOEMBOLICA. ASPECTOS GENÉTICOS, BIOLÓGICOS Y CLÍNICOS

Abstract

The central role of the platelet in the arterial thrombosis is largely known. In the recent years, the platelet involvement in the initiation and development of venous thromboembolism (VTE) has been described and widely discussed._x000D_ The main objective of this thesis has been the characterization of the platelet parameters in healthy population, as well as the estimation of their genetic determination or heritability (h2). In addition, the association of various platelet parameters with the risk of VTE have been described._x000D_ We have used two types of sample: the Genetic Analysis of Idiopathis Thrombophilia 2 (2 GAIT) project, a study of 35 families, and the project called Riesgo de Enfermedad TROmboembólica VEnosa (RETROVE), a prospective case–control of unrelated individuals._x000D_ The Study #1 has established the normal ranges for the platelet counts and indices, immature platelet fraction (IPF) and platelet function (PFA), representative of the healthy Spanish population healthy, part of the GAIT 2 project. The linear mixed models have led to the conclusion that there are variations in platelet counts and volumes between children (2–12 years) and the other groups of age (years 13–93). The platelet function remains constant throughout the life due in part to the inverse relationship between platelet count and the mean platelet volume. Moreover, the PFA parameters did not vary during the life. The parameters of volume and IPF shown similar behaviour with respect to age (increase) and gender (do not vary)._x000D_ The framework of the Study #2 is the GAIT 2 project. The main objective of this family–based study is the identification of genes that determine the variability of the parameters related to the VTE risk. The GAIT 2 project has replicated the h2 of the venous thrombosis already described in GAIT 1 project. Also, we determined the h2 platelet counts, and indices, IPF and PFA._x000D_ The framework of the Studies #3 and #4 are the RETROVE project. The Study #3 has identified the association between the risk of VTE and various platelet parameters using generalized linear regression models. In this regard, the association between risk of VTE and higher counts of platelet and plateletcrit in women has been described. In the Study #4, the increase in the platelet function analysed by aggregometry in whole blood (MultiplateTM) has been not associated with the risk of thrombosis. On the other hand, the platelet function evaluated by the PFA–100® analyser whether has been able to detect of the VTE risk, thereby that it is a highly useful method to evaluate of the risk of VTE.

Date of Award	26 Sept 2017
Original language	Spanish
Supervisor	Nuria Pujol Moix (Director) & Juan Carlos Souto Andres (Director)