Studio dell'aggregazione piastrinica con aggregometro ad elettrodi multipli (multiplate) e della disfunzione endoteliale con tecnica ecocolorDoppler in soggetti trombofilici

Background: the link between venous thromboembolism (VTE) and arterial thromboembolic events (ATE) is still uncertain. In 2003 Prandoni et al published the first study that reported a connection, in term of etiopathogenesis between VTE and atherosclerosis. During the last few years several other study confirm this association, that could be attributed to common risk factors for the two conditions. The contribution of thrombophilic defects to the link between VTE and ATE has yet to be defined. Thrombophilic conditions (hereditary deficiencies of protein S, protein C and antithrombin) have been recognized as most potent thrombophilic conditions for VTE. Whether hereditary protein S, Protein C or antithrombin deficiency also are involved in the development of ATE need to be confirmed and the evidence of a possible association has been showed mainly from case reports. Blood haemostasis is a complex mechanism influenced from coagulation factors, aggregation proteins, blood cells (platelets, leucocytes) and vascular endothelium. Most of biochemical tests focused on coagulation system asses only a part of this complex mechanism and, in particular, the laboratory tests analyze only the coagulations cascade. But the role of platelets and vascular endothelium is not clear. The contribution of thrombophilic defects as common risk factor between VTE and ATE has yet to be defined compared with nondeficient family members. Moreover in this study the endothelial dysfunction could be the real cause for both conditions VTE and ATE. There are no data concerning the role of platelets function or vascular endothelium function in this thrombophilic patients population. The aim of the study is to define, in thrombophilic patients (Prot C, Prot S and antithrombin defects) compared with non-deficient family members. the role of platelets function using a new analyzer named Multiplate® whole blood aggregometry that evaluated platelets aggregations in whole blood and to define also the possible implication of endothelial function, by the non-invasive assessment of flow mediated dilatation (FMD) of the brachial artery, by B-mode ultrasonography, using a standardized procedure Material and Methods: after signing an informed consent, we enrolled patients with thrombophilic defects (cases) and create three subgroups (cases with deficit of protein C, protein S and antithrombin) with and without a history of thromboembolic disease, and subjects without thrombophilic defects (controls). We collected baseline data of all (cases and controls) on previous episodes of VTE and ATE, risk factors for atherosclerosis (i.e. hypertension, diabetes mellitus, cigarette smoking; hyperlipidemia) All patients were tested for thrombophilic defects in addition to their index deficiencies (FV Leiden, G20210 A prothrombin, lupus anticoagulant; PC and PS, AT). Moreover, we study platelets aggregations with a new analyzer named Multiplate® whole blood aggregometry that evaluated platelets aggregations in whole blood with thrombin inibitor (irudin); this instrument identify the electrical impedance (as area under curve, AUC) caused from platelets aggregation. The platelets aggregation was triggered by different activators: adenosine-5 diphosphate (ADP test), arachidonic acid (ASPI test) and thrombin receptor activatin peptide (TRAP -6) All cases and controls underwent evaluation of endothelial function by the non-invasive assessment of flow mediated dilatation (FMD) of the brachial artery, by B-mode ultrasonography, using a standardized procedure. Results: patients with thromphilic defects versus controls have similar demographical charatistics. The valutation of the platelets aggregation by Multiplate® with different tests (ASPI, ADP and TRAP) show a different in the two groups but it is no statistically significant; we observed the same results if analyze the three subgroups (Protein C defects, Protein S and antithrombin deficiency) protein separately. The ultrasonography evaluation of endothelial function show that there is a reduction of the flow mediated dilatation (FMD) in patients with thrombophilic defects versus controls. The FMD calculated in thrombophilic patients is statistically significant (3.7±0.5% vs 5.2±0.6% ,p value = 0.015) compared the controls. Discussion: Our preliminary data show that in patients with thrombophilic deficiency there is increased of platelets aggregation but it’s no statically significant. This results is confirm also in all different subgroups of thromphilic deficiency (Prot C, S, and AT deficiency ). However an endothelial dysfunction is showed in thrombophilic patients compared the controls. Although we speculated with this data, as other study have reported, that endothelial dysfunction rather than coagulation disorders is the main actor in the link between VTE and ATE in thrombophilic subjects. It is yet unclear the role of the different actors (endothelium dysfunction, platelet aggregation and coagulation factors) in the development on VTE and ATE, but this study can show that endothelium dysfunction can be one of the most important trigger factor in the thrombophilic patient