Diego Mezzano - Academia.edu (original) (raw)
Papers by Diego Mezzano
Rev Med Chile, Aug 1, 1994
Resumo: Aiming to study the applicability and reproducibility of four comercial kits used for the... more Resumo: Aiming to study the applicability and reproducibility of four comercial kits used for the serological detection of Chagas disease (Chagatest-Inst Invest Paraguay, Ortho Chagas, Abbott Chagas (ELISA tests) and Estabilgen Hemo Chagas (indirect hemagglutination test ...
Arthritis Research & Therapy, 2015
Systemic sclerosis (SSc) is a chronic autoimmune disease characterized by microvascular damage, i... more Systemic sclerosis (SSc) is a chronic autoimmune disease characterized by microvascular damage, inflammation, and fibrosis. It has become increasingly evident that platelets, beyond regulating hemostasis, are important in inflammation and innate immunity. Platelets may be an important source of proinflammatory and profibrotic cytokines in the vascular microenvironment. In this study, we sought to assess the contribution of platelet-derived factors in patients with SSc to the angiogenesis of human dermal microvascular endothelial cells (DMVECs) in a tubule formation assay and to characterize the secretion of profibrotic and proinflammatory cytokines in these platelets. We analyzed platelets obtained from 30 patients with SSc and 12 healthy control subjects. Angiogenesis was evaluated in vitro with a DMVEC tubule formation assay on Matrigel and platelet-derived angiogenic factors such as vascular endothelial growth factor (VEGF), 165b isoform (VEGF165b), and cytokine secretion was evaluated. Platelet serotonin content was also determined. When DMVECs were incubated with SSc platelet releasates, tubule formation was significantly inhibited (p < 0.01, t test), and higher expression of endothelin-1 in these cells was observed compared with control subjects (p < 0.05, Mann-Whitney U test). In SSc platelet releasates, VEGF165b was significantly higher (p < 0.05, t test), and the VEGF165b/VEGF ratio was increased compared with that of control subjects. Higher secretion of transforming growth factor β (p < 0.01, t test) and CD40L (p < 0.01, t test) was observed compared with control subjects. Also, intraplatelet serotonin levels were lower in platelets obtained from patients with diffuse SSc compared with patients with limited SSc and control subjects (p < 0.05, t test). Our findings suggest that antiangiogenic factors such as VEGF165b, together with proinflammatory and profibrotic factors secreted by platelets, can contribute to the progression of peripheral microvascular damage, defective vascular repair, and fibrosis in patients with SSc.
Blood Coagulation Fibrinolysis an International Journal in Haemostasis and Thrombosis, Oct 1, 2010
The common F12 -4 C&a... more The 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.
Annals of Hematology, Jun 9, 2010
Metabolic Syndrome and Related Disorders, 2015
Metabolic syndrome, a chronic condition associated with higher risk of cardiovascular diseases, i... more Metabolic syndrome, a chronic condition associated with higher risk of cardiovascular diseases, is increasingly prevalent in young adults. Dyslipidemia, proinflammatory cytokines, endothelial dysfunction signs, and RhoA/Rho-kinase (ROCK) activation are considered risk factors of cardiovascular diseases. The occurrence of these factors in young patients with metabolic syndrome but without type 2 diabetes or hypertension has not been fully studied. The objective of this study was to evaluate young subjects with enlarged waist circumference and dyslipidemia but without type 2 diabetes or hypertension,for markers associated with a higher risk of cardiovascular diseases. Thirty-two male patients aged 31 ± 1.3 years diagnosed with metabolic syndrome according to the National Cholesterol Education Program Adult Treatment Panel III guide for enlarged waist circumference, elevated triglycerides, and low HDL levels, but with blood pressure and fasting glucose within normal ranges, were evaluated for RhoA/ROCK activity in leukocytes, serum fatty acid methyl esters profile, proinflammatory cytokines, and oxidative stress markers in addition to thrombin generation and biochemical analysis. Age- and gender-matched healthy subjects were equivalently evaluated. Patients showed higher RhoA/ROCK activity, elevated levels of interleukin-6, soluble CD40L, monocyte chemoattractant protein, and high-sensitivity C-reactive protein (P < 0.001) as well as parameters of endogenous thrombin generation potential (P < 0.05) compared with healthy subjects. Increased thiobarbituric acid reactive substances, advanced oxidation protein product, and insulin levels and low nitric oxide biodisponibility (P < 0.001) were also found in patients as compared with controls. Palmitic acid was one of the saturated fatty acids found to be significantly elevated in patients compared with control subjects (P = 0.0087). Increased markers of cardiovascular risk are already present in young adults with metabolic syndrome but without type 2 diabetes or hypertension.
Hematology / the Education Program of the American Society of Hematology. American Society of Hematology. Education Program, 2012
Congenital mild bleeding disorders (MBDs) are very prevalent and are the source of frequent diagn... more Congenital mild bleeding disorders (MBDs) are very prevalent and are the source of frequent diagnostic problems. Most MBDs are categorized as disorders of primary hemostasis (ie, type 1 VWD and platelet function disorders), but mild or moderate deficiencies of clotting factors and some rare hyperfibrinolytic disorders are also included. These patients have abnormal bleeding from the skin and mucous membranes, menorrhagia, and disproportionate hemorrhages after trauma, invasive procedures, and surgery. This review addresses the main problems that physicians and hemostasis laboratories confront with the diagnosis of these patients, including: discerning normal/appropriate from pathological bleeding, the role and yield of screening tests, the lack of distinctive bleeding pattern among the different diseases, the inherent difficulties in the diagnosis of type 1 VWD and the most common platelet functional disorders, improvements in assays to measure platelet aggregation and secretion, an...
Revista médica de Chile, 1984
Thrombosis and haemostasis, 2002
Journal of Thrombosis and Haemostasis, 2014
Please select Five Mandatory Key Words from the <a <a href="
European Journal of Biochemistry, 1990
To gain insight into the mechanism by which long-chain acyl-CoA thioesters potentiate diacylglyce... more To gain insight into the mechanism by which long-chain acyl-CoA thioesters potentiate diacylglycerol-activated protein kinase C, the cofactor dependence of this activating effect was studied with purified rat brain enzyme and histone H1 as substrate. Using two different assay systems, palmitoyl-CoA was found to decrease greatly the amount of phosphatidylserine required to activate the kinase. No relative changes were observed in the dependence of the enzyme for other cofactors (diacylglycerol, ATP, and Ca2+) in the presence of palmitoyl-CoA. The potentiating effect of palmitoyl-CoA and the decrease in phosphatidylserine requirement of the kinase was also demonstrated using the 47-kDa protein of human platelets as substrate and platelet protein kinase C as source of enzyme. The acyl-CoA thioester of the carcinogenic peroxisome-proliferator ciprofibrate was also found to decrease the phosphatidylserine requirement of protein kinase C. The data suggest that acyl-CoAs may play a role in the regulation of protein kinase C activity.
Transfusion, 1982
... In preparing platelet-rich plasma (PRP) by differential centrifu-gation, a significant number... more ... In preparing platelet-rich plasma (PRP) by differential centrifu-gation, a significant number of platelets are lost in the red blood cell fraction and in ... galactan (Stractan) gradient, which com-prised about 10 to 15 percent of total platelets, appeared to survive far longer in viv&amp;#x27;o (3 14 ...
Thrombosis Research, 1995
Seminars in Thrombosis and Hemostasis, 2009
The major advances from research on platelet molecular and cell biology, physiology, and pathophy... more The major advances from research on platelet molecular and cell biology, physiology, and pathophysiology over the past decades
Seminars in Thrombosis and Hemostasis, 2008
Patients with inherited mucocutaneous bleeding (MCB) pose frequent and significant diagnostic cha... more Patients 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.
Pathophysiology of Haemostasis and Thrombosis, 2003
Two groups (21 healthy young male each) received either Mediterranean-type diet (MD) or high-fat ... more Two groups (21 healthy young male each) received either Mediterranean-type diet (MD) or high-fat diet(HFD) during 90 days. Between days 30-60, both diets were supplemented with 240 ml/day of red wine. MD alone was associated with: lower plasma fibrinogen (p=0.03), factor VIIc (p=0.034) and factor VIIIc (p=0.0057); higher levels of protein S (p=0.013); longer BT (p=0.017); and marginal increases in platelet serotonin aggregation and secretion after stimulation with epinephrine. Red wine supplementation in both diets, resulted in lower plasma fibrinogen (p=0.001) and factor VIIc (p=0.05), and in increased t-PA (p=0.01) and PAI-1 (p=0.0003). The effects of wine on antithrombin III (p=0.01) were divergent, with a decrease in the HFD group and an increase in the MD group. No effects of diet or wine were detected in plasma proteins C and S, BT or VWF:Ag. Wine supplementation also resulted in a significant increase in ex vivo platelet aggregation and secretion after stimulation with collagen (1 and 2 g/ml, p&amp;amp;amp;lt;=0.01).MD and moderate consumption of red wine have complementary,mostly beneficial effects on haemostatic CV risk factors. The longer BT in individuals on MD, independently of red wine, would denote less interaction of platelets with the vascular wall, which would be beneficial from the point of view of CV risk. However,the increased platelet aggregation/secretion after wine intake, possibly a &amp;amp;amp;quot;rebound&amp;amp;amp;quot; phenomenon, would be a risk factor for thrombosis.
Nature Clinical Practice Nephrology, 2007
Journal of Thrombosis and Haemostasis, 2014
Only ± 50% of patients with type 1 von Willebrand disease (VWD) have recognized molecular defects... more Only ± 50% of patients with type 1 von Willebrand disease (VWD) have recognized molecular defects and diagnosis still rests on demonstrating low plasma von Willebrand factor (VWF) protein/function. However, no generalized consensus exists regarding the type and number of VWF variables that should be considered for diagnosis. To compare the quantitative impact of four different criteria to diagnose type 1 VWD. We tested four laboratory criteria on 4298 laboratory studies during a 5-year period. The first was the National Heart, Lung, and Blood Institute recommendation, which diagnoses type 1 VWD with plasma VWF antigen (VWF:Ag) and VWF ristocetin cofactor (VWF:RCo) < 30 IU dL(-1) and possible VWD/'low VWF' with values between 30 and 50 IU dL(-1) . Second, diagnosis was established when two of three variables, VWF:Ag, VWF:RCo, VWF collagen binding assay (VWF:CB), were ≤ 2.5th percentile. Diagnostic criterion for possible VWD/'low VWF' using percentiles was also described. The third criterion (European Group on von Willebrand Disease, EUVWD), uses a plasma level of VWF:RCo (or VWF:CB) ≤ 40 IU dL(-1) for diagnosis. Finally, the Zimmerman Program for the Molecular and Clinical Biology of VWD (ZPMCBVWD) diagnoses VWD if VWF:Ag or VWF:RCo are ≤ 40 IU dL(-1) . The three assays had high correlation and excellent agreement at levels < 120 IU dL(-1) . The National Heart, Lung, and Blood Institute recommendation was followed to diagnose 122 (2.8%) patients with type 1 VWD and 704 (16.4%) with possible VWD/'low VWF.' Using percentiles, the diagnosis of type 1 VWD increased to 280 (6.5%) patients; 169 (3.9%) patients had possible VWD and 180 (4.2%) patients had 'low VWF.' Diagnoses using EUVWD and ZPMCBVWD criteria increased to 339 (7.9%) and 357 (8.3%) patients, respectively. Identical data, analyzed using different criteria, led to almost three-fold difference (2.8-8.3%) in diagnostic rate. This increase is mostly explained by increasing the cut-off values of VWF measurements from < 30 to ≈ 40 IU dL(-1) . Further refinement of the laboratory diagnosis of type 1 VWD is a priority.
Journal of Thrombosis and Haemostasis, 2007
Rev Med Chile, Aug 1, 1994
Resumo: Aiming to study the applicability and reproducibility of four comercial kits used for the... more Resumo: Aiming to study the applicability and reproducibility of four comercial kits used for the serological detection of Chagas disease (Chagatest-Inst Invest Paraguay, Ortho Chagas, Abbott Chagas (ELISA tests) and Estabilgen Hemo Chagas (indirect hemagglutination test ...
Arthritis Research & Therapy, 2015
Systemic sclerosis (SSc) is a chronic autoimmune disease characterized by microvascular damage, i... more Systemic sclerosis (SSc) is a chronic autoimmune disease characterized by microvascular damage, inflammation, and fibrosis. It has become increasingly evident that platelets, beyond regulating hemostasis, are important in inflammation and innate immunity. Platelets may be an important source of proinflammatory and profibrotic cytokines in the vascular microenvironment. In this study, we sought to assess the contribution of platelet-derived factors in patients with SSc to the angiogenesis of human dermal microvascular endothelial cells (DMVECs) in a tubule formation assay and to characterize the secretion of profibrotic and proinflammatory cytokines in these platelets. We analyzed platelets obtained from 30 patients with SSc and 12 healthy control subjects. Angiogenesis was evaluated in vitro with a DMVEC tubule formation assay on Matrigel and platelet-derived angiogenic factors such as vascular endothelial growth factor (VEGF), 165b isoform (VEGF165b), and cytokine secretion was evaluated. Platelet serotonin content was also determined. When DMVECs were incubated with SSc platelet releasates, tubule formation was significantly inhibited (p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.01, t test), and higher expression of endothelin-1 in these cells was observed compared with control subjects (p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.05, Mann-Whitney U test). In SSc platelet releasates, VEGF165b was significantly higher (p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.05, t test), and the VEGF165b/VEGF ratio was increased compared with that of control subjects. Higher secretion of transforming growth factor β (p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.01, t test) and CD40L (p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.01, t test) was observed compared with control subjects. Also, intraplatelet serotonin levels were lower in platelets obtained from patients with diffuse SSc compared with patients with limited SSc and control subjects (p &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.05, t test). Our findings suggest that antiangiogenic factors such as VEGF165b, together with proinflammatory and profibrotic factors secreted by platelets, can contribute to the progression of peripheral microvascular damage, defective vascular repair, and fibrosis in patients with SSc.
Blood Coagulation Fibrinolysis an International Journal in Haemostasis and Thrombosis, Oct 1, 2010
The common F12 -4 C&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;a... more The common F12 -4 C&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;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 &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 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 &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 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 &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 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&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;gt;T polymorphism on hemostatic tests widely used in routine clinical practice.
Annals of Hematology, Jun 9, 2010
Metabolic Syndrome and Related Disorders, 2015
Metabolic syndrome, a chronic condition associated with higher risk of cardiovascular diseases, i... more Metabolic syndrome, a chronic condition associated with higher risk of cardiovascular diseases, is increasingly prevalent in young adults. Dyslipidemia, proinflammatory cytokines, endothelial dysfunction signs, and RhoA/Rho-kinase (ROCK) activation are considered risk factors of cardiovascular diseases. The occurrence of these factors in young patients with metabolic syndrome but without type 2 diabetes or hypertension has not been fully studied. The objective of this study was to evaluate young subjects with enlarged waist circumference and dyslipidemia but without type 2 diabetes or hypertension,for markers associated with a higher risk of cardiovascular diseases. Thirty-two male patients aged 31 ± 1.3 years diagnosed with metabolic syndrome according to the National Cholesterol Education Program Adult Treatment Panel III guide for enlarged waist circumference, elevated triglycerides, and low HDL levels, but with blood pressure and fasting glucose within normal ranges, were evaluated for RhoA/ROCK activity in leukocytes, serum fatty acid methyl esters profile, proinflammatory cytokines, and oxidative stress markers in addition to thrombin generation and biochemical analysis. Age- and gender-matched healthy subjects were equivalently evaluated. Patients showed higher RhoA/ROCK activity, elevated levels of interleukin-6, soluble CD40L, monocyte chemoattractant protein, and high-sensitivity C-reactive protein (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001) as well as parameters of endogenous thrombin generation potential (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.05) compared with healthy subjects. Increased thiobarbituric acid reactive substances, advanced oxidation protein product, and insulin levels and low nitric oxide biodisponibility (P &amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt; 0.001) were also found in patients as compared with controls. Palmitic acid was one of the saturated fatty acids found to be significantly elevated in patients compared with control subjects (P = 0.0087). Increased markers of cardiovascular risk are already present in young adults with metabolic syndrome but without type 2 diabetes or hypertension.
Hematology / the Education Program of the American Society of Hematology. American Society of Hematology. Education Program, 2012
Congenital mild bleeding disorders (MBDs) are very prevalent and are the source of frequent diagn... more Congenital mild bleeding disorders (MBDs) are very prevalent and are the source of frequent diagnostic problems. Most MBDs are categorized as disorders of primary hemostasis (ie, type 1 VWD and platelet function disorders), but mild or moderate deficiencies of clotting factors and some rare hyperfibrinolytic disorders are also included. These patients have abnormal bleeding from the skin and mucous membranes, menorrhagia, and disproportionate hemorrhages after trauma, invasive procedures, and surgery. This review addresses the main problems that physicians and hemostasis laboratories confront with the diagnosis of these patients, including: discerning normal/appropriate from pathological bleeding, the role and yield of screening tests, the lack of distinctive bleeding pattern among the different diseases, the inherent difficulties in the diagnosis of type 1 VWD and the most common platelet functional disorders, improvements in assays to measure platelet aggregation and secretion, an...
Revista médica de Chile, 1984
Thrombosis and haemostasis, 2002
Journal of Thrombosis and Haemostasis, 2014
Please select Five Mandatory Key Words from the <a <a href="
European Journal of Biochemistry, 1990
To gain insight into the mechanism by which long-chain acyl-CoA thioesters potentiate diacylglyce... more To gain insight into the mechanism by which long-chain acyl-CoA thioesters potentiate diacylglycerol-activated protein kinase C, the cofactor dependence of this activating effect was studied with purified rat brain enzyme and histone H1 as substrate. Using two different assay systems, palmitoyl-CoA was found to decrease greatly the amount of phosphatidylserine required to activate the kinase. No relative changes were observed in the dependence of the enzyme for other cofactors (diacylglycerol, ATP, and Ca2+) in the presence of palmitoyl-CoA. The potentiating effect of palmitoyl-CoA and the decrease in phosphatidylserine requirement of the kinase was also demonstrated using the 47-kDa protein of human platelets as substrate and platelet protein kinase C as source of enzyme. The acyl-CoA thioester of the carcinogenic peroxisome-proliferator ciprofibrate was also found to decrease the phosphatidylserine requirement of protein kinase C. The data suggest that acyl-CoAs may play a role in the regulation of protein kinase C activity.
Transfusion, 1982
... In preparing platelet-rich plasma (PRP) by differential centrifu-gation, a significant number... more ... In preparing platelet-rich plasma (PRP) by differential centrifu-gation, a significant number of platelets are lost in the red blood cell fraction and in ... galactan (Stractan) gradient, which com-prised about 10 to 15 percent of total platelets, appeared to survive far longer in viv&amp;#x27;o (3 14 ...
Thrombosis Research, 1995
Seminars in Thrombosis and Hemostasis, 2009
The major advances from research on platelet molecular and cell biology, physiology, and pathophy... more The major advances from research on platelet molecular and cell biology, physiology, and pathophysiology over the past decades
Seminars in Thrombosis and Hemostasis, 2008
Patients with inherited mucocutaneous bleeding (MCB) pose frequent and significant diagnostic cha... more Patients 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.
Pathophysiology of Haemostasis and Thrombosis, 2003
Two groups (21 healthy young male each) received either Mediterranean-type diet (MD) or high-fat ... more Two groups (21 healthy young male each) received either Mediterranean-type diet (MD) or high-fat diet(HFD) during 90 days. Between days 30-60, both diets were supplemented with 240 ml/day of red wine. MD alone was associated with: lower plasma fibrinogen (p=0.03), factor VIIc (p=0.034) and factor VIIIc (p=0.0057); higher levels of protein S (p=0.013); longer BT (p=0.017); and marginal increases in platelet serotonin aggregation and secretion after stimulation with epinephrine. Red wine supplementation in both diets, resulted in lower plasma fibrinogen (p=0.001) and factor VIIc (p=0.05), and in increased t-PA (p=0.01) and PAI-1 (p=0.0003). The effects of wine on antithrombin III (p=0.01) were divergent, with a decrease in the HFD group and an increase in the MD group. No effects of diet or wine were detected in plasma proteins C and S, BT or VWF:Ag. Wine supplementation also resulted in a significant increase in ex vivo platelet aggregation and secretion after stimulation with collagen (1 and 2 g/ml, p&amp;amp;amp;lt;=0.01).MD and moderate consumption of red wine have complementary,mostly beneficial effects on haemostatic CV risk factors. The longer BT in individuals on MD, independently of red wine, would denote less interaction of platelets with the vascular wall, which would be beneficial from the point of view of CV risk. However,the increased platelet aggregation/secretion after wine intake, possibly a &amp;amp;amp;quot;rebound&amp;amp;amp;quot; phenomenon, would be a risk factor for thrombosis.
Nature Clinical Practice Nephrology, 2007
Journal of Thrombosis and Haemostasis, 2014
Only ± 50% of patients with type 1 von Willebrand disease (VWD) have recognized molecular defects... more Only ± 50% of patients with type 1 von Willebrand disease (VWD) have recognized molecular defects and diagnosis still rests on demonstrating low plasma von Willebrand factor (VWF) protein/function. However, no generalized consensus exists regarding the type and number of VWF variables that should be considered for diagnosis. To compare the quantitative impact of four different criteria to diagnose type 1 VWD. We tested four laboratory criteria on 4298 laboratory studies during a 5-year period. The first was the National Heart, Lung, and Blood Institute recommendation, which diagnoses type 1 VWD with plasma VWF antigen (VWF:Ag) and VWF ristocetin cofactor (VWF:RCo) < 30 IU dL(-1) and possible VWD/'low VWF' with values between 30 and 50 IU dL(-1) . Second, diagnosis was established when two of three variables, VWF:Ag, VWF:RCo, VWF collagen binding assay (VWF:CB), were ≤ 2.5th percentile. Diagnostic criterion for possible VWD/'low VWF' using percentiles was also described. The third criterion (European Group on von Willebrand Disease, EUVWD), uses a plasma level of VWF:RCo (or VWF:CB) ≤ 40 IU dL(-1) for diagnosis. Finally, the Zimmerman Program for the Molecular and Clinical Biology of VWD (ZPMCBVWD) diagnoses VWD if VWF:Ag or VWF:RCo are ≤ 40 IU dL(-1) . The three assays had high correlation and excellent agreement at levels < 120 IU dL(-1) . The National Heart, Lung, and Blood Institute recommendation was followed to diagnose 122 (2.8%) patients with type 1 VWD and 704 (16.4%) with possible VWD/'low VWF.' Using percentiles, the diagnosis of type 1 VWD increased to 280 (6.5%) patients; 169 (3.9%) patients had possible VWD and 180 (4.2%) patients had 'low VWF.' Diagnoses using EUVWD and ZPMCBVWD criteria increased to 339 (7.9%) and 357 (8.3%) patients, respectively. Identical data, analyzed using different criteria, led to almost three-fold difference (2.8-8.3%) in diagnostic rate. This increase is mostly explained by increasing the cut-off values of VWF measurements from < 30 to ≈ 40 IU dL(-1) . Further refinement of the laboratory diagnosis of type 1 VWD is a priority.
Journal of Thrombosis and Haemostasis, 2007