Summary. Background: Prophylaxis of venous thromboembolism (VTE) in hospitalized medical patients is largely underused. We sought to assess the value of a simple risk assessment model (RAM) for the identification of patients at risk of VTE. Methods: In a prospective cohort study, 1180 consecutive patients admitted to a department of internal medicine in a 2-year period were classified as having a high or low risk of VTE according to a predefined RAM. They were followed-up for up to 90 days to assess the occurrence of symptomatic VTE complications. The primary study outcome was to assess the adjusted hazard ratio (HR) of VTE in high-risk patients who had adequate in-hospital thromboprophylaxis in comparison with those who did not, and that of VTE in the latter group in comparison with low-risk patients. Results: Four hundred and sixty-nine patients (39.7%) were labelled as having a high risk of thrombosis. VTE developed in four of the 186 (2.2%) who received thromboprophylaxis, and in 31 of the 283 (11.0%) who did not (HR of VTE, 0.13; 95% CI, 0.04-0.40). VTE developed also in two of the 711 (0.3%) low-risk patients (HR of VTE in high-risk patients without prophylaxis as compared with lowrisk patients, 32.0; 95% CI, 4.1-251.0). Bleeding occurred in three of the 186 (1.6%) high-risk patients who had thromboprophylaxis. Conclusions: Our RAM can help discriminate between medical patients at high and low risk of VTE. The adoption of adequate thromboprophylaxis in high-risk patients during hospitalization leads to longstanding protection against thromboembolic events with a low risk of bleeding.

BackgroundThrombotic complications in Sickle Cell Disease (SCD) arise since infancy, but the role of the coagulation system in children has been poorly explored. To determine its role in the development of clinical complications in childhood we measured coagulation and endothelial parameters in children with SCD at steady state.MethodsMarkers of thrombin generation, fibrin dissolution and endothelial activation were evaluated in 38 children with SS-Sβ°, 6 with SC disease and 50 age and blood group matched controls. Coagulation variables were correlated with markers of hemolysis and inflammation, with the presence of cerebral and lung vasculopathy and with the frequency of clinical complications.ResultsSS-Sβ° patients presented higher levels of factor VIII, von Willebrand factor antigen (VWF:Ag) and collagen binding activity, tissue plasminogen activator antigen (t-PA:Ag), D-dimer, p-selectin, prothrombin fragment1+2 (F1+2) and lower ADAMTS-13:activity/VWF:Ag (p<0.05) compared to controls and SC patients. In SS-Sβ° patients coagulation variables correlated positively with markers of inflammation, hemolysis, and negatively with HbF (p<0.05). Patients with cerebral silent infarcts showed significant decrease in t-PA:Ag and ADAMTS-13 Antigen and a tendency toward higher D-dimer, F1+2, TAT compared to patients without them. D-dimer was associated with a six fold increased risk of cerebral silent infarcts. No correlation was found between coagulation activation and large vessel vasculopathy or other clinical events except for decreased t-PA:Ag in patients with tricuspid Rigurgitant Velocity >2.5m/sec.ConclusionsSS-Sβ° disease is associated with extensive activation of the coagulation system at steady state since young age. ADAMTS-13 and t-PA:Ag are involved in the development of cerebral silent infarcts.

Activation of endothelial cells and platelets is an initial step toward the development of cardiovascular disease. Erectile dysfunction (ED) may be an early manifestation of endotheliopathy. We evaluated the effects of tadalafil on cyclic nucleotides (cGMP and cAMP) and soluble adhesion molecules (E- and P-selectin [ES and PS]). The patients were divided into 2 groups on the basis of the presence (10 patients) or absence (9 patients) of cardiovascular risk factors (dyslipidemia, hypertension, and smoking). Nitric oxide (NO) was unmeasurable in all the patients. Tadalafil administration induced a significant increase in cGMP levels in both groups (P < .01). In contrast, cAMP significantly increased (P < .05) and PS decreased (P < .01) only in patients without cardiovascular risk factors. Tadalafil induced a beneficial effect on platelet activation in patients with ED without cardiovascular risk factors; this effect was not mediated by NO.

Nowadays long-term outcome of heart transplantation is limited by a peculiar type of coronary atherosclerosis, known as cardiac allograft vasculopathy (CAV). Although the exact pathogenesis of CAV remains unclear, emerging evidence indicates that the endothelium plays a significant role in the onset and progression of this disease. Nitric oxide (NO) is the principal mediator of all endothelial protective effects, due to its antinflammatory, antiproliferative, immunomodulatory and vasorelaxant properties. CAV involves immunologic mechanisms operating in the context of common cardiovascular risk factors which lead to impaired endothelial function, mainly as a consequence of decreased NO bioavailability and excessive oxidative stress. Once dysfunctional, the endothelium promotes CAV lesion progression towards the diffuse narrowing of the coronary vasculature which characterizes advanced allograft vasculopathy. Recently, many studies showed the possibility to restore endothelial dysfunction with an associated potential improvement in clinical cardiovascular outcome. Therefore, growing interest deserves the possibility to exert an endothelial protective role shown by some currently used cardiovascular and immunosuppressive drugs, as well as the future development of new pharmacological compounds with selective endothelial protective properties as a target for successful prevention and therapy of CAV.