Browsing by Author "Panes, O"

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    Cardiovascular risk factors in vegetarians: Normalization of hyperhomocysteinemia with vitamin B-12 and reduction of platelet aggregation with n-3 fatty acids
    (PERGAMON-ELSEVIER SCIENCE LTD, 2000) Mezzano, D; Kosiel, K; Martinez, C; Cuevas, A; Panes, O; Aranda, E; Strobel, P; Perez, DD; Pereira, J; Rozowski, J; Leighton, F
    Hyperhomocysteinemia in association with vitamin B-12 deficiency, and increased platelet aggregation, probably due to dietary lack of n-3 fatty acids, constitute cardiovascular risk factors frequently observed in vegetarians. We tested if administration of vitamin B-12 normalizes the concentration of total plasma homocysteine, and if intake of eicosapentaenoic (20:5n-3) and docosahexaenoic (22:6n-3) fatty acids modulates platelet function in a population of lactoovovegetarians. One week after a single intramuscular injection of cyanocobalamin (10000 mug) in 18 individuals, serum vitamin B-12 increased from 149+/-63 pg/mL to 532+/-204 pg/mL (p<0.0001) and total tHcy dropped from 12.4+/-4.7 to 7.9+/-3.1 mol/L (p<0.0001). Ten of fourteen of these vegetarians completed an 8-week supplementation with 700 mg/day of each eicosapentaenoic and docosahexaenoic acids. Increased incorporation of these fatty acids into plasma lipids was observed in all of them, together with a significant reduction in maximum percentage or slope of platelet aggregation with all the agonists tested (ADP, epinephrin, collagen, arachidonic acid). No significant change in bleeding time was observed after n-3 fatty acid trial. Supplementation with vitamin B-12 and n-3 fatty acids corrects hyperhomocysteinemia and reduces platelet reactivity to agonists in vegetarians. Whether this supplementation improves the already reduced cardiovascular morbidity and mortality associated with vegetarian diet has yet to be demonstrated. (C) 2000 Elsevier Science Ltd. All rights reserved.
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    Circulating platelet-derived microparticles in systemic lupus erythematosus - Association with increased thrombin generation and procoagulant state
    (GEORG THIEME VERLAG KG, 2006) Pereira, J; Alfaro, G; Goycoolea, M; Quiroga, T; Ocqueteau, M; Massardo, L; Perez, C; Saez, C; Panes, O; Matus, V; Mezzano, D
    The risk for thrombosis is significantly increased in systemic lupus erythematosus (SLE), affecting both venous and arterial vessels. Activated platelets are known to participate in thrombus formation and growth. A general feature of activated cells is the shedding of microparticles (MP) which support coagulation by exposure of negatively charged phospholipids and possibly tissue factor (TF). In this work we characterized circulating MP in patients with SLE and their relationship with a procoagulant state. Thirty patients with SLE (aged 15-72 years, mean age 38 years) and 20 healthy controls (aged 22-54 years, mean age 34 years) were studied; patients fulfilled 4 revised criteria for SLE. The number and cellular source of circulating MP were determined by flow cytometry using double labeling with specific monoclonal antibodies and annexin V. Thrombin generation was measured as the endogenous thrombin potential (ETP) without the addition of exogenous phospholipids and TF; under these conditions the generation of thrombin depended directly on the number of MP present in plasma. Thrombin anti-thrombin (TAT) and plasmin-antiplasmin (PAP) complexes were measured by ELISA. Compared to the controls, circulating MP were significantly elevated in the patient group (1218 +/- 136 vs 653 +/- 74 x 10(3)/ml plasma, p: 0.0007). In both groups, most of these MP were of platelet origin (927 +/- 131 vs 517 +/- 72 x 10(3)/ml plasma, p:0.009). ETP was higher among patients as compared to the controls (804 +/- 64 vs 631 +/- 37 nM thrombin, p: 0.025). Plasma levels of TAT in patients and controls were 3.4 +/- 0.8 and 1.4 +/- 0.5 mu g/L, respectively (p:0.04), and of PAP complexes were 62.5 +/- 14 and 24.05 +/- 2.5 mu g/ml, respectively (p:0.014). The number of platelet-derived MP correlated significantly with thrombin generation (r: 0.42; p: 0.038) and TAT levels (r: 0.40; p: 0.035). We did not find an association of circulating MP with disease activity nor with the presence of antiphospholipid antibodies. The increased number of circulating platelet-derived microparticles and their association with high ETP and activation of the coagulation system suggest that these microparticles play an important role in the pathogenesis of the prothrombotic state in SLE patients.
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    Hemostatic disorder of uremia: The platelet defect, main determinant of the prolonged bleeding time, is correlated with indices of activation of coagulation and fibrinolysis
    (GEORG THIEME VERLAG KG, 1996) Mezzano, D; Tagle, R; Panes, O; Perez, M; Downey, P; Munoz, B; Aranda, E; Barja, P; Thambo, S; Gonzalez, F; Mezzano, S; Pereira, J
    Several parameters of primary hemostasis and markers of activation of coagulation and fibrinolysis were measured in 38 patients with severe (creatinine clearance <20 ml/min) chronic renal failure (CRF) without dialysis and diseases or drugs affecting hemostasis. Bleeding time (BT) was prolonged in 25/48 patients, and was correlated with age of patients, severity of renal failure, hematocrit, impairment in platelet aggregation-secretion and decrease in platelet ATP content. Defects in von Willebrand factor played no role in the prolongation of the BT. Multivariate analysis showed that only platelet dysfunction and severity of renal disease were independent predictors of the BT in uremia. The platelet functional disorder was significantly correlated with a reduction in platelet ATP and ADP.
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    Inflammation, not hyperhomocysteinemia, is related to oxidative stress and hemostatic and endothelial dysfunction in uremia
    (BLACKWELL SCIENCE INC, 2001) Mezzano, D; Pais, EO; Aranda, E; Panes, O; Downey, P; Ortiz, M; Tagle, R; Gonzalez, F; Quiroga, T; Caceres, MS; Leighton, F; Pereira, J
    Background. Several cardiovascular risk factors are present in patients with chronic renal failure (CRF), among which are systemic inflammation and hyperhomocysteinemia. Increased oxidative stress, endothelial activation/dysfunction, and coagulation activation are considered integral components of the inflammatory response, but have also been proposed as mediators of plasma homocysteine (tHcy)-induced cell damage. Using correlation analysis, we assessed the relative contributions of inflammation and hyperhomocysteinemia in the abnormal oxidative stress, endothelial activation/dysfunction, and hemostasis activation in patients with CRF.
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    Tranexamic acid inhibits fibrinolysis, shortens the bleeding time and improves platelet function in patients with chronic renal failure
    (F K SCHATTAUER VERLAG GMBH, 1999) Mezzano, D; Panes, O; Munoz, B; Pais, E; Tagle, R; Gonzalez, F; Mezzano, S; Barriga, F; Pereira, J
    Background: A defect in platelet function is the main determinant of the prolonged bleeding time in chronic renal failure (CRF). We previously reported a significant correlation between platelet abnormalities and elevated plasma markers of plasmin and thrombin generation. Our aim was to explore thr effect of inhibiting both plasmin action with tranexamic acid (TA) and thrombin production with low molecular weight heparin (LMWH), on the bleeding time (BT) and platelet function in patients with CRF. Methods: 37 patients with CRF (mean creatinine 8.6 +/- 4.4 mg/dl) under conservative treatment, with prolonged BT, entered this study and received TA during 6 days, with (n = 24) and without LMWH (n = 13). BT, platelet aggregation/secretion, platelet granule contents, von Willebrand factor and parameters of coagulation and fibrinolysis were recorded before and at the end of treatment. Results: The BT was shortened in 26/37 (67%) patients. This effect was associated with significant improvement of platelet aggregation and secretion, with decrease to a normal range of fibrin/fibrinogen degradation products, mild increase in plasmin-antiplasmin complexes and pronounced reduction of circulating plasminogen. No differences were seen among patients with or without LMWH. No serious side effects or complications were observed. Interpretation: These findings indicate that the activation of fibrinolysis plays a significant role in the defect of primary hemostasis in patients with CRF. inhibition of plasmin activity with TA shortens the BT and improves platelet function in the majority of patients with severe disease.