Browsing by Author "Pereira, Jaime"
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- ItemAortic Stenosis and Acquired von Willebrand Disease: Lack of Association(W B SAUNDERS CO-ELSEVIER INC, 2011) Carrasco, Esperanza; Lopez, Rodrigo; Rattalino, Marcos; Lema, Guillermo; Pereira, Jaime; Canessa, Roberto; Zalaquett, Ricardo; Carvajal, Claudia; Carrasco, PauloObjectives: The association between aortic stenosis (AS) and acquired von Willebrand disease type 2A has been described. It may be present in up to 90% of patients with AS. Shear stress has been proposed as the underlying mechanism; however, the physiopathology of this condition is not completely understood. No specific treatment has been studied in this specific population besides aortic valve replacement (AVR). As a coadjuvant therapy, some cardiac surgery centers use desmopressin routinely. The authors report the first stage of an ongoing study designed to compare the effects of desmopressin versus placebo in patients with severe AS scheduled for AVR. Because of the different incidences of the acquired von Willebrand type 2A reported in the literature, the first stage was conducted to describe the incidence of this clinical association in the present population, allowing the sample size for the second stage of the study to be obtained.
- ItemASH, ABHH, ACHO, Grupo CAHT, Grupo CLAHT, SAH, SBHH, SHU, SOCHIHEM, SOMETH, Sociedad Panamena de Hematologia, SPH, and SVH 2021 guidelines for management of venous thromboembolism in Latin America(ELSEVIER, 2021) Neumann, Ignacio; Izcovich, Ariel; Aguilar, Ricardo; Leon Basantes, Guillermo; Casais, Patricia; Colorio, Cecilia C.; Guillermo Esposito, Maria Cecilia; Garcia Lazaro, Pedro P.; Meillon Garcia, Luis A.; Pereira, Jaime; Rezende, Suely Meireles; Carlos Serrano, Juan; Tejerina Valle, Mario L.; Vera, Felipe; Karzulovic, Lorena; Rada, Gabriel; Schuenemann, HolgerBackground: Venous thromboembolism (VTE) is a common disease in Latin American settings. Implementing international guidelines in Latin American settings requires additional considerations.
- ItemClot lysis time in platelet-rich plasma: Method assessment, comparison with assays in platelet-free and platelet-poor plasmas, and response to tranexamic acid(TAYLOR & FRANCIS INC, 2012) Panes, Olga; Padilla, Oslando; Matus, Valeria; Saez, Claudia G.; Berkovits, Alejandro; Pereira, Jaime; Mezzano, DiegoFibrinolysis dysfunctions cause bleeding or predisposition to thrombosis. Platelets contain several factors of the fibrinolytic system, which could up or down regulate this process. However, the temporal relationship and relative contributions of plasma and platelet components in clot lysis are mostly unknown. We developed a clot lysis time (CLT) assay in platelet-rich plasma (PRP-CLT, with and without stimulation) and compared it to a similar one in platelet-free plasma (PFP) and to another previously reported test in platelet-poor plasma (PPP). We also studied the differential effects of a single dose of tranexamic acid (TXA) on these tests in healthy subjects. PFP- and PPP-CLT were significantly shorter than PRP-CLT, and the three assays were highly correlated (p < 0.0001). PFP- and PPP-, but more significantly PRP-CLT, were positively correlated with age and plasma PAI-1, von Willebrand factor, fibrinogen, LDL-cholesterol, and triglycerides (p < 0.001). All these CLT assays had no significant correlations with platelet aggregation/secretion, platelet counts, and pro-coagulant tests to explore factor X activation by platelets, PRP clotting time, and thrombin generation in PRP. Among all the studied variables, PFP-CLT was independently associated with plasma PAI-1, LDL-cholesterol, and triglycerides and, additionally, stimulated PRP-CLT was also independently associated with plasma fibrinogen. A single 1 g dose of TXA strikingly prolonged all three CLTs, but in contrast to the results without the drug, the lysis times were substantially shorter in non-stimulated or stimulated PRP than in PFP and PPP. This standardized PRP-CLT may become a useful tool to study the role of platelets in clot resistance and lysis. Our results suggest that initially, the platelets enmeshed in the clot slow down the fibrinolysis process. However, the increased clot resistance to lysis induced by TXA is overcome earlier in platelet-rich clots than in PFP or PPP clots. This is likely explained by the display of platelet pro-fibrinolytic effects. Focused research is needed to disclose the mechanisms for the relationship between CLT and plasma cholesterol and its potential pathophysiologic and clinical relevance.
- ItemDaño vascular asociado a uso de cocaína. Caso clínico(SOC MEDICA SANTIAGO, 2012) Massardo, Teresa; Pino, Angela; Berrocal, Isabel; Castro, Gabriel; Prat, Hernan; Pereira, JaimeCocaine abuse is associated with an increased risk of cardiac and cerebro vascular events, such as myocardial infarction, sudden cardiac death, and ischemic stroke. The underlying mechanisms leading to these complications are not fully understood although intravascular thrombus formation and accelerated atherosclerosis are prominent findings. We report a 39-year-old male addicted to cocaine, who presented with three consecutive ischemic events characterized by an acute myocardial infarction and two ischemic strokes complicated by cardiac failure and severe neurological sequelae. The pathophysiology of cocaine-induce vascular damage and the management of the ischemic complications are discussed. (Rev Med Chile 2012; 140: 507-511).
- ItemHigh prevalence of bleeders of unknown cause among patients with inherited mucocutaneous bleeding. A prospective study of 280 patients and 299 controls(FERRATA STORTI FOUNDATION, 2007) Quiroga, Teresa; Goycoolea, Manuela; Panes, Olga; Aranda, Eduardo; Martinez, Carlos; Belmont, Sabine; Munoz, Blanca; Zuniga, Pamela; Pereira, Jaime; Mezzano, DiegoBackground and Objectives
- ItemHuman platelets synthesize and express functional tissue factor(AMER SOC HEMATOLOGY, 2007) Panes, Olga; Matus, Valeria; Saez, Claudia G.; Quiroga, Teresa; Pereira, Jaime; Mezzano, DiegoThe source and significance of bloodborne tissue factor (TF) are controversial. TF mRNA, protein, and TF-dependent procoagulant activity (PCA) have been detected in human platelets, but direct evidence of TF synthesis is missing. Nonstimulated monocyte-free platelets from most patients expressed TF mRNA, which was enhanced or induced in all of them after platelet activation. Immunoprecipitation assays revealed TF protein (mainly of a molecular weight [Mr] of approximately 47 kDa, with other bands of approximately 35 and approximately 60 kDa) in nonstimulated platelet membranes, which also increased after activation. This enhancement was concomitant with TF translocation to the plasma membrane, as demonstrated by immunofluorescence-confocal microscopy and biotinylation of membrane proteins. Platelet PCA, assessed by factor Xa (FXa) generation, was induced after activation and was inhibited by 48% and 76% with anti-TF and anti-FVIIa, respectively, but not by intrinsic pathway inhibitors. Platelets incorporated [35S]-methionine into TF proteins with Mr of approximately 47 kDa, approximately 35 kDa, and approximately 60 kDa, more intensely after activation. Puromycin but not actinomycin D or DRB (5,6-dichloro-1 -beta-D-ribofuranosylbenzimidazole)inhibited TIF neosynthesis. Thus, human platelets not only assemble the clotting reactions on their membrane, but also supply their own TIF for thrombin generation in a timely and spatially circumscribed process. These observations simplify, unify, and provide a more coherent formulation of the current cellbased model of hemostasis.
- ItemIdentification of Statin’s Action in a Small Cohort of Patients with Major Depression(2021) Thakkar, Ishani; Massardo, Teresa; Pereira, Jaime; Quintana, Juan Carlos; Risco, Luis; Saez, Claudia G.; Corral, Sebastián; Villa, Carolina; Spuler, Jane; Olivares, Nixa; Valenzuela, Guillermo; Castro, Gabriel; Riedel, Byron; Vicentini, Daniel; Muñoz, Diego; Lastra, Raúl; Rodriguez-Fernandez, MariaStatins are widely used as an effective therapy for ischemic vascular disorders and employed for primary and secondary prevention in cardiac and cerebrovascular diseases. Their hemostatic mechanism has also been shown to induce changes in cerebral blood flow that may result in neurocognitive improvement in subjects with Major Depressive Disorder. Behavioral data, various blood tests, and resting-state brain perfusion data were obtained at the start of this study and three months post-therapy from a small cohort of participants diagnosed with Major Depressive Disorder. Subjects received either rosuvastatin (10 mg) or placebo with their standard selective serotonin reuptake inhibitors therapy. At the end of the study, patients using rosuvastatin reported more positive mood changes than placebo users. However, standard statistical tests revealed no significant differences in any non-behavioral variables before and after the study. In contrast, feature selection techniques allowed identifying a small set of variables that may be affected by statin use and contribute to mood improvement. Classification models built to assess the distinguishability between the two groups showed an accuracy higher than 85% using only five selected features: two peripheral platelet activation markers, perfusion abnormality in the left inferior temporal gyrus, Attention Switching Task Reaction latency, and serum phosphorus levels. Thus, using machine learning tools, we could identify factors that may be causing self-reported mood improvement in patients due to statin use, possibly suggesting a regulatory role of statins in the pathogenesis of clinical depression.
- ItemIncreased number of circulating endothelial cells and plasma markers of endothelial damage in chronic cocaine users(PERGAMON-ELSEVIER SCIENCE LTD, 2011) Saez, Claudia G.; Olivares, Paulina; Pallavicini, Julio; Panes, Olga; Moreno, Natalia; Massardo, Teresa; Mezzano, Diego; Pereira, JaimeBackground: Cocaine use has been related with the development of accelerated atherosclerosis and with an increased risk of cardiac and cerebrovascular events, such as myocardial infarction, sudden cardiac death, and ischemic stroke. The underlying mechanisms leading to these complications are not fully understood, although thrombus formation and altered vascular function are prominent findings.
- ItemInfluence of the F12-4 C > T polymorphism on hemostatic tests(LIPPINCOTT WILLIAMS & WILKINS, 2010) Corral, Javier; Anton, Ana I.; Quiroga, Teresa; Gonzalez Conejero, Rocio; Pereira, Jaime; Roldan, Vanessa; Vicente, Vicente; Mezzano, DiegoThe common F12 - 4 C>T polymorphism significantly regulates plasma levels of FXII, the first element of the intrinsic pathway of coagulation. Due to the robust effects that this pathway has on blood coagulation in vitro, the objective of our study was to evaluate the influence of this polymorphism on different hemostatic tests. We studied 46 hemostatic parameters in 566 participants: 280 patients with mucocutaneous bleeding and 286 controls. The F12 - 4T allele, associated with reduced levels of FXII (P<0.001), also significantly delayed the activated partial thromboplastin time (aPTT) expressed as aPTTr (ratio sample plasma/normal pooled plasma). Thus, both patients and controls carrying the T allele had higher aPTTr than C/C homozygous individuals (P<0.001). Interestingly, 92% of healthy controls who had prolonged aPTTr carried the F12 - 4T allele. Moreover, individuals with the F12 - 4T allele also had less thrombin generation (assessed by endogenous thrombin potential, thrombin peak and time to achieve the peak of thrombin) using a test with low tissue factor concentration and explicit contact phase activation. Finally, both patients and controls carrying the F12 - 4T allele also displayed significantly lower FIXc and FVIIc levels than C/C individuals (P<0.01). For all associations except for FVIIc, a gene-dosage effect was observed, and homozygous TT individuals had the farthest values. Our study reveals a significant effect of the F12 - 4 C>T polymorphism on hemostatic tests widely used in routine clinical practice. Blood Coagul Fibrinolysis 21: 632-639 (c) 2010 Wolters Kluwer Health | Lippincott Williams & Wilkins.
- ItemLaboratory Assessment of Familial, Nonthrombocytopenic Bleeding: A Definitive Not Possible Mucocutaneous Diagnosis Is Often Not Possible(THIEME MEDICAL PUBL INC, 2008) Pereira, Jaime; Quiroga, Teresa; Mezzano, DiegoPatients with inherited mucocutaneous bleeding (MCB) pose frequent and significant diagnostic challenges. Bleeding symptoms are frequent among the otherwise healthy population, and the clinical distinction between normal subjects and patients with genuine bleeding disorders is complex. Screening or global laboratory assays are nonspecific and have low sensitivity to detect mild bleeding disorders. Moreover, there are inherent difficulties in diagnosing von Willebrand disease and platelet function defects, the best-characterized and most frequent disorders of primary hemostasis. On the other hand, some patients with moderate to severe clotting factor deficiencies and those with increased fibrinolysis usually present with MCB. Finally, in a significant proportion of patients, the definitive diagnosis is not possible even after an extensive laboratory workup. This article reviews the clinical and laboratory approach to the diagnosis of patients presenting with MCB, the limitations of the available methodologies to evaluate the clinical significance of bleeding, and the diagnostic yield of global and specific hemostasis tests used to investigate these patients.
- ItemMultimodal assessment of acute cardiac toxicity induced by thoracic radiotherapy in cancer patients : study protocol(2021) Merino Lara, Tomas Rodrigo; Pinto, Mauricio P.; Orellana Vargas, María Paz; Martínez, Gonzalo; Andía Kohnenkampf, Marcelo Edgardo; Muñoz Schuffenegger, Pablo; Acevedo Claros, Francisco Nicolás; Gabrielli, Luigi; Sánchez Rojel, César Giovanni; Pereira, JaimeBackground : Today, cancer ranks as one of the leading causes of death. Despite the large number of novel available therapies, radiotherapy (RT) remains as the most effective non-surgical method to cure cancer patients. In fact, approximately 50% of all cancer patients receive some type of RT and among these 60% receive RT-treatment with a curative intent. However, as occurs with any other oncological therapy, RT treated patients may experience toxicity side effects that range from moderate to severe. Among these, cardiotoxicity represents a significant threat for premature death. Current methods evaluate cardiotoxic damage based on volumetric changes in the Left Ventricle Ejected Fraction (LVEF). Indeed, a 10% drop in LVEF is commonly used as indicator of cardiotoxicity. More recently, a number of novel techniques have been developed that significantly improve specificity and sensitivity of heart’s volumetric changes and early detection of cardiotoxicity even in asymptomatic patients. Among these, the Strain by Speckle Tracking (SST) is a technique based on echocardiographic analysis that accurately evaluates myocardial deformation during the cardiac cycle (ventricular and atrial function). Studies also suggest that Magnetic Resonance Imaging (MRI) is a high-resolution technique that enables a better visualization of acute cardiac damage. Methodology: This protocol will evaluate changes in SST and MRI in cancer patients that received thoracic RT. Concomitantly, we will assess changes in serum biomarkers of cardiac damage in these patients, including: high-sensitivity cardiac Troponin-T (hscTnT), N-Terminal pro-Brain Natriuretic Peptide (NTproBNP) and Circulating Endothelial Cells (CECs), a marker of endothelial dysfunction and vascular damage. Discussion: The presented protocol is to our knowledge the first to prospectively and with a multimodal approach, study serological and image biomarkers off early cardiac damage due to radiotherapy. With a practical clinical approach we will seek early changes that could potentially be in the future be linked to clinical mayor events with consequences for cancer survivors.
- ItemPlatelet activation in chronic cocaine users: Effect of short term abstinence(TAYLOR & FRANCIS INC, 2011) Pereira, Jaime; Saez, Claudia G.; Pallavicini, Julio; Panes, Olga; Pereira Flores, Karla; Cabreras, Manuel J.; Massardo, Teresa; Mezzano, DiegoCocaine abuse increases the risk of cardiac and cerebrovascular events, such as myocardial infarction and ischemic stroke. The underlying mechanisms leading to these complications are not fully understood although intravascular thrombus formation has been observed. The aim of this study was to investigate the existence of platelet activation and the effect of short-term abstinence in chronic cocaine consumers. We studied 23 cocaine dependent individuals (aged 20-54 years) who met DSM-IV criteria for cocaine dependence and 20 controls. Samples were obtained at baseline, within 72 h of last drug exposure and after 4 weeks of controlled abstinence. Monocyte-platelet aggregates (MPA) were measured by flow cytometry. Plasma levels of soluble CD40L (sCD40L), Neutrophil-Activating Peptide-2 (NAP-2) and regulated on activation normal T cells expressed and secreted (RANTES) were determined by ELISA. Levels of MPA, sCD40L, NAP-2 and RANTES were significantly higher (all p < 0.05) in cocaine addicts compared to controls at baseline. All the parameters returned to values similar to the control group after 4-weeks' abstinence. Levels of sCD40L and RANTES were associated with an index of intensity of drug consumption (p < 0.02). Our results demonstrate that cocaine use induces platelet activation which is a prominent finding after recent consumption. The persistence over time of this condition may contribute not only to acute thrombotic complications but also to the development of early-onset atherosclerotic process observed in cocaine abusers.
- ItemProcarboxypeptidase U (TAFI) and the Thr325Ile proCPU polymorphism in patients with hereditary mucocutaneous hemorrhages(ELSEVIER, 2009) Matus, Valeria; Willemse, Johan; Quiroga, Teresa; Goycoolea, Manuela; Aranda, Eduardo; Panes, Olga; Pereira, Jaime; Hendriks, Dirk; Mezzano, DiegoBackground: Patients with hereditary mucocutaneous bleeding are difficult to diagnose and many of them fulfill the category of bleeders of unknown cause (BUC). The pathogenic role of hyperfibrinolysis has received little attention, despite the successful use of antifibrinolytic drugs in treating many of these patients. Theoretically, decreased plasma procarboxypeptidase U (proCPU) levels or lower carboxypeptidase U (CPU) stability would result in higher fibrinolytic activity and bleeding tendency.
- ItemUtilidad de una encuesta para identificar donantes de sangre de zonas no endémicas, potencialmente infectados con Trypanosoma cruzi(1999) Vásques, Marcela; Vidal, Sylvia; Espinoza, Claudia; Palomo, Iván; Torres, Marisa; Alvarado, Christian; Canales, Marinela; Salinas, Ana María; Pereira, Jaime; Jerez, GuillermoLarge numbers of immigrants from endemic areas for Chagas' disease resided in Maule Region and transmission can occur by blood transfusion.is important evaluated the usefulness of a questionnaire for identifying Trypanosoma cruzi infected blood donors in nonendemic area. In this work participate blood donors of 7 hospitals of the Region. During the 6-month period, 1.581 blood donors were asked and their samples were analysed for T. cruzi antibodies.The effectiveness of the questionnaire was evaluated by comparing donor's answers about their risk for Chagas' disease with the result of testing with an enzyme-linked immunosorbent assay. Positives samples were confirm by: indirect immunofluorescence, and polymerase chain reaction. Only one donor was positive to Chagas' disease. This donors reported no risk factors. Therefore blood donors seropositive for T. cruzi are presente in donors population of nonendemic area without the usual identifiable risk factors.
- ItemVal/Leu(247) and Trp/Ser(316) polymorphisms in beta(2) glycoprotein I and their association with thrombosis in unselected Chilean patients(SPRINGER, 2007) Palomo, Ivan; Pereira, Jaime; Alarcon, Marcelo; Vasquez, Marcela; Pinochet, Carmen; Poblete, Fernando; Mendez, Evelyn; Sandoval, Jeannette; Vidal, Rolando; Pierangeli, SilviaIt is known that polymorphisms of beta (2)-glycoprotein I (beta (2)GPI) in exon 7 affect interaction between the phospholipid binding site and the antibodies, and that other polymorphisms in exon 8 increase the generation of antibodies. In this study, we analyzed genetic polymorphisms of beta (2)GPI in unselected Chilean patients to determine the prevalence of beta (2)GPI polymorphisms in the phospholipid domain in patients with venous and arterial thrombosis and the clinical correlation with thromboembolic complications. This study comprised 149 patients with venous and arterial thrombosis (62 with venous thrombosis and 87 with arterial thrombosis) and 160 healthy controls with no previous history of thrombosis. Polymorphisms of exons 7 and 8 of beta (2)GPI, which encode for its fifth domain, were determined by PCR-RFLP. The presence of aPL or anti-beta (2)GPI in the patients was detected by ELISA. Anti-beta (2)GPI were present in 8/149 patients (5.4%); of these, five had aCL antibodies of low titer. The allele containing Val/Leu(247) and Trp/Ser(316) was significantly more frequent in patients with thrombosis than in the control group (OR=3.1, CI 1.6-6.0, p=0.0003; OR=2.9, CI 1.1-8.6, p=0.027, respectively). These polymorphisms did not correlate with aPL or anti-beta (2)GPI but significant differences were observed with venous thrombosis (p=< 0.0001) and arterial thrombosis (p=0.026). In conclusion, the beta (2)GPI polymorphisms Val/Leu(247) and Trp/Ser(316) are not related to the presence of anti-beta (2)GPI antibodies in unselected Chilean patients with venous and arterial thrombosis, but they are significantly associated with venous and arterial thrombosis.