High plasma levels of soluble P-Selectin and Factor VIII predict venous thromboembolism in non-small cell lung cancer patients: The Thrombo-Nsclc risk score.

INTRODUCTION: Venous thromboembolism (VTE) is common in non-small cell lung cancer (NSCLC) patients undergoing systemic chemotherapy. The usefulness of Khorana score (KRS) to predict risk in lung cancer patients is limited, and the identification of patients who would benefit most from thromboprophylaxis is challenging. We aimed to identify variables whose values before chemotherapy helped in predicting VTE occurrence, and build a model to assess VTE risk. MATERIALS AND METHODS: A cohort of newly diagnosed NSCLC patients to undergo outpatient chemotherapy, not under anticoagulant treatment, was recruited. Pre-chemotherapy demographic, clinical, analytical and tumor-specific variables were collected. Patients were prospectively followed-up for 12 months to record VTE events. Bivariate and multivariate analyses were performed to identify VTE-associated variables, and a prediction model was built and compared with KRS. RESULTS: 90 patients were recruited, 18 of whom had a VTE event during follow-up. High baseline levels of factor VIII (FVIII) and, especially, soluble P-selectin (sP-selectin), were independently associated with VTE risk (hazard ratio [HR] 4.15, 95% confidence interval [CI] 1.17-14.71, and 66.40 [8.70-506.69], respectively). Our so-called Thrombo-NSCLC risk score, which assigns 1 and 3 points to high FVIII and sP-selectin values, respectively, was significantly better than KRS in predicting VTE (area under the curve [AUC] 0.93 vs. 0.55, sensitivity 94.4 vs. 35.0%, specificity 93.1 vs. 60.0%). Our prediction model showed significant discriminating capacity between high risk vs. intermediate/low risk patients, while KRS did not. CONCLUSIONS: The Thrombo-NSCLC risk score may be useful to identify those NSCLC patients who would benefit most from thromboprophylaxis.

Factor Xa Inhibition by Rivaroxaban Modified Mitochondrial-Associated Proteins in Human Abdominal Aortic Aneurysms.

BACKGROUND: The presence of intraluminal thrombus and mitochondrial dysfunction in human abdominal aortic aneurysms (AAAs) have been associated with aneurysmal growth and rupture. The objective of the study was to study if endogenous factor Xa (FXa) may modulate mitochondrial functionality and expression of proteins associated with mitophagy in human AAAs. METHODS: AAA sites with intraluminal thrombus were obtained from 6 patients undergoing elective AAA surgery repair. Control samples were collected from 6 organ donors. The effect of FXa was analyzed by in vitro incubation of AAA with 50 nmol/L rivaroxaban, an oral FXa inhibitor. RESULTS: The enzymatic activities of citrate synthase, a biomarker of mitochondrial density, and cytochrome C oxidase, a biomarker of mitochondrial respiratory chain functionality, were significantly reduced in the AAA sites with respect to the healthy aorta (citrate synthase activity in µU/min/µg protein: control: 3.51 ± 0.22 vs. AAA: 0.37 ± 0.15.; P < 0.01; cytochrome C oxidase activity in µOD/min/µg protein: control: 8.05 ± 1.57 vs. AAA: 3.29 ± 1.05; P < 0.05). The addition of rivaroxaban to AAA reverted the activity of both citrate synthase and cytochrome C oxidase to similar values to control. Mitochondrial Drp-1 expression was higher in AAA sites than in either control aortas or rivaroxaban-incubated AAA sites. Cytosolic content of Drp-1 phosphorylated at Ser637, mitochondrial Parkin, and mitochondrial PINK1-Parkin interaction were significantly reduced in the AAA sites with respect to control aortas. For all these parameters, rivaroxaban-incubated AAA showed similar values compared with control aortas. CONCLUSIONS: In human AAA, rivaroxaban improved mitochondrial functionality that was associated with changes in proteins related to mitophagy. Its opens possible new effects of endogenous FXa on the mitochondria in the human AAA site.

Effects of hormones on platelet aggregation.

Platelets and their activation/inhibition mechanisms play a central role in haemostasis. It is well known agonists and antagonists of platelet activation; however, during the last years novel evidences of hormone effects on platelet activation have been reported. Platelet functionality may be modulated by the interaction between different hormones and their platelet receptors, contributing to sex differences in platelet function and even in platelet-mediated vascular damage. It has suggested aspects that apparently are well established should be reviewed. Hormones effects on platelet activity are included among them. This article tries to review knowledge about the involvement of hormones in platelet biology and activity.

Serenoa repens treatment modifies bax/bcl-2 index expression and caspase-3 activity in prostatic tissue from patients with benign prostatic hyperplasia.

PURPOSE: Permixon is a lipidosterolic extract of Serenoa repens (SR) widely used to treat men with benign prostatic hyperplasia (BPH). We tested the effect of this drug on molecular mechanisms associated with apoptosis, such as the Bax-to-Bcl-2 expression ratio and caspase-3 activity, in prostatic tissue from men with symptomatic BPH treated for 3 months before surgery. MATERIALS AND METHODS: An open, multicenter pilot study of 2 parallel groups of patients with BPH was done. They were randomized to be followed for 3 weeks without any treatment before surgery (control group) or to receive 160 mg SR orally twice daily for a 3-month period preceding the same surgery. Surgery was ultimately performed in 17 controls and 12 patients by transurethral prostate resection or retropubic adenomectomy. Bax and Bcl-2 expression, and caspase-3 activity were determined by Western blot in 15 controls and 10 patients, and reported in blinded fashion. RESULTS: The Bax-to-Bcl-2 ratio, which is used as an apoptotic index, was significantly increased in the prostatic tissue of treated patients. The level of the intact 116 kDa poly (adenosine diphosphate-ribose) polymerase form, an enzyme involved in the cell death apoptotic pathway, was also found to be decreased in prostatic tissue from SR treated patients, suggesting increased caspase 3 activity in the prostate. CONCLUSIONS: Permixon increased molecular markers involved in the apoptotic process, ie the Bax-to-Bcl-2 expression ratio and caspase-3 activity. This could have clinical relevance due to the improvement in symptoms produced by treatment with this drug.