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OBJECTIVES: The present study aimed to develop strategies for genotyping DO*HY (Dombrock system) and DI*A/DI*B (Diego system) alleles and to evaluate the impact of genomic and self-declared ancestry on rare donor screening in admixed populations. BACKGROUND: The antigens Hy and Dib demonstrate clinical importance. The lack of antisera for the serological evaluation of these antigens makes it necessary to develop molecular methods. In addition, considering that some rare red blood cell phenotypes present differences in frequency between ethnic groups, it is important to assess the applicability of self-declared ancestry in the search for rare donors in admixed populations. METHODS: DO*HY and DI*A/DI*B genotyping based on real-time polymerase chain reaction (PCR) was standardised. A total of 457 blood donors clustered by self-defined skin colour/race categories were genotyped. Furthermore, individual genomic ancestry was used in the analyses. RESULTS: The assays developed are reproducible and provide satisfactory results even at low concentrations of DNA, which make them useful in situations where the DNA is scarce, such as dried blood spots on filter paper, or when screening for pooled samples. No significant difference was observed in the frequencies of the DI*A, DI*B and DO*HY, comparing the self-declared White (branco) donors with those who are Black (preto) and Brown (pardo). CONCLUSION: Real-time PCR, especially using pooled samples, is a promising strategy to screen rare blood donors. Although both self-reported race/colour and some blood group phenotypes are associated with ancestry, the results point to a greater complexity in the application of self-declared race/colour in the screening of rare donors in admixed populations.
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Donantes de Sangre , Antígenos de Grupos Sanguíneos/genética , Tipificación y Pruebas Cruzadas Sanguíneas , Selección de Donante , Etnicidad/genética , Técnicas de Genotipaje , Autoinforme , Femenino , Humanos , MasculinoRESUMEN
BACKGROUND: The most common microcytic and hypochromic anemias are iron deficiency anemia and thalassemia trait. Several indices to discriminate iron deficiency anemia from thalassemia trait have been proposed as simple diagnostic tools. However, some of the best discriminative indices use parameters in the formulas that are only measured in modern counters and are not always available in small laboratories. The development of an index with good diagnostic accuracy based only on parameters derived from the blood cell count obtained using simple counters would be useful in the clinical routine. Thus, the aim of this study was to develop and validate a discriminative index to differentiate iron deficiency anemia from thalassemia trait. METHODS: To develop and to validate the new formula, blood count data from 106 (thalassemia trait: 23 and iron deficiency: 83) and 185 patients (thalassemia trait: 30 and iron deficiency: 155) were used, respectively. Iron deficiency, ß-thalassemia trait and α-thalassemia trait were confirmed by gold standard tests (low serum ferritin for iron deficiency anemia, HbA2>3.5% for ß-thalassemia trait and using molecular biology for the α-thalassemia trait). RESULTS: The sensitivity, specificity, efficiency, Youden's Index, area under receiver operating characteristic curve and Kappa coefficient of the new formula, called the Matos & Carvalho Index were 99.3%, 76.7%, 95.7%, 76.0, 0.95 and 0.83, respectively. CONCLUSION: The performance of this index was excellent with the advantage of being solely dependent on the mean corpuscular hemoglobin concentration and red blood cell count obtained from simple automatic counters and thus may be of great value in underdeveloped and developing countries.
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BACKGROUND: We evaluated the association between plasma levels of VWF, ADAMTS13 and d-Dimer, which consist on endothelial dysfunction and hypercoagulability biomarkers, and cystatin C with retinopathy in type 1 diabetic patients. METHODS: Patients were classified according to presence (n=55) or absence (n=70) of retinopathy. Plasma levels of VWF, ADAMTS13, d-Dimer and cystatin C were evaluated by ELISA and ADAMTS13 activity was evaluated by FRET. RESULTS: Plasma levels of VWF (p=0.033), ADAMTS13 activity (p=0.014), d-Dimer (p=0.002) and cystatin C (p<0.001) were elevated in diabetic patients with retinopathy compared to those without this complication. The multivariate logistic regression analysis showed that ADAMTS13 activity (p=0.031) d-Dimer (p=0.015) and cystatin C (p=0.001) remained associated with retinopathy after adjustment for age, diabetes duration, use of statin, use of ACEi or angiotensin antagonist, use of acetylsalicylic acid and glomerular filtration rate. CONCLUSION: ADAMTS13 activity, d-Dimer and cystatin C are associated with retinopathy in type 1 diabetic patients and are promising biomarkers for the diagnosis and monitoring of diabetic retinopathy.
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Proteína ADAMTS13/sangre , Cistatina C/sangre , Diabetes Mellitus Tipo 1/complicaciones , Retinopatía Diabética/sangre , Retinopatía Diabética/complicaciones , Desintegrinas/sangre , Productos de Degradación de Fibrina-Fibrinógeno/análisis , Factor de von Willebrand/análisis , Proteína ADAMTS13/metabolismo , Adulto , Diabetes Mellitus Tipo 1/sangre , Diabetes Mellitus Tipo 1/diagnóstico , Retinopatía Diabética/diagnóstico , Ensayo de Inmunoadsorción Enzimática , Femenino , Transferencia Resonante de Energía de Fluorescencia , Humanos , Masculino , Adulto JovenRESUMEN
Previously we investigated the tissue factor (TF)-dependent coagulation pathway and key haemostatic cofactors in white women with preeclampsia (P-EC) and suggested that plasma factor VII (FVII) levels can differentiate women with P-EC from healthy nonpregnant women or normal pregnant women, at the same trimester, with high sensitivity, specificity, positive and negative predictive values. Here we re-examine the TF-dependent pathway in a large cohort of Brazilian women. A total of 240 women were studied. These included healthy nonpregnant women (nâ=â79), normotensive pregnant women (nâ=â80) and women with severe P-EC (nâ=â81). Commercially available enzyme-linked immunosorbent assays were used to measure plasma FVII, activated factor VII (FVIIa), TF and tissue factor pathway inhibitor (TFPI). All study participants were matched for age. Pregnant women (with/without P-EC) were matched for gestational age and parity. Plasma levels of FVII, FVIIa and TFPI were significantly increased in women with severe P-EC compared with healthy nonpregnant women (Pâ<â0.01) or normotensive pregnant women (Pâ<â0.01). FVIIa was also higher in normotensive pregnant women compared with nonpregnant women (Pâ<â0.01). However, no such significant trends were observed for plasma TF levels (Pâ=â0.074). In conclusion, circulating FVII, FVIIa and TFPI were significantly elevated in women with severe P-EC in the absence of comparable changes in plasma TF levels. The present work is in agreement with our previous report on FVII levels in white women with P-EC. Thus, this lends further support to the notion that plasma FVII levels are potentially valuable diagnostic marker for P-EC, irrespective of ethnicity.
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Factor VII/genética , Factor VIIa/genética , Lipoproteínas/genética , Preeclampsia/sangre , Preeclampsia/diagnóstico , Tromboplastina/genética , Adulto , Coagulación Sanguínea , Presión Sanguínea , Brasil , Estudios de Casos y Controles , Estudios de Cohortes , Factor VII/metabolismo , Factor VIIa/metabolismo , Femenino , Expresión Génica , Humanos , Lipoproteínas/sangre , Preeclampsia/genética , Preeclampsia/patología , Embarazo , Índice de Severidad de la Enfermedad , Tromboplastina/metabolismoRESUMEN
BACKGROUND: The most common microcytic and hypochromic anemias are iron deficiency anemia and thalassemia trait. Several indices to discriminate iron deficiency anemia from thalassemia trait have been proposed as simple diagnostic tools. However, some of the best discriminative indices use parameters in the formulas that are only measured in modern counters and are not always available in small laboratories. The development of an index with good diagnostic accuracy based only on parameters derived from the blood cell count obtained using simple counters would be useful in the clinical routine. Thus, the aim of this study was to develop and validate a discriminative index to differentiate iron deficiency anemia from thalassemia trait. METHODS: To develop and to validate the new formula, blood count data from 106 (thalassemia trait: 23 and iron deficiency: 83) and 185 patients (thalassemia trait: 30 and iron deficiency: 155) were used, respectively. Iron deficiency, ß-thalassemia trait and a-thalassemia trait were confirmed by gold standard tests (low serum ferritin for iron deficiency anemia, HbA2 > 3.5% for ß-thalassemia trait and using molecular biology for the a-thalassemia trait). RESULTS: The sensitivity, specificity, efficiency, Youden's Index, area under receiver operating characteristic curve and Kappa coefficient of the new formula, called the Matos & Carvalho Index were 99.3%, 76.7%, 95.7%, 76.0, 0.95 and 0.83, respectively. CONCLUSION: The performance of this index was excellent with the advantage of being solely dependent on the mean corpuscular hemoglobin concentration and red blood cell count obtained from simple automatic counters and thus may be of great value in underdeveloped and developing countries.
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Humanos , Masculino , Femenino , Adolescente , Adulto , Persona de Mediana Edad , Anciano , Rasgo Drepanocítico , Talasemia/diagnóstico , Anemia Ferropénica/diagnósticoRESUMEN
BACKGROUND: Preeclampsia (PE) is a pregnancy disease associated with exacerbated inflammatory response. Annexin A1 (AnxA1) is a glucocorticoid-regulated protein endowed with anti-inflammatory and proresolving properties that has been much studied in various animal models of inflammation but poorly studied in the context of human inflammatory diseases. The main objective of this study was to measure AnxA1 levels in PE women and to compare those levels in normotensive pregnant and non-pregnant women. We evaluated the association among AnxA1, ultrasensitive C reactive protein (us-CRP) and soluble tumor necrosis factor alpha receptor type 1 (sTNF-R1) plasma levels of the study participants. METHODS: This study included 40 non-pregnant, 38 normotensive pregnant and 51 PE women. PE women were stratified in early (N = 23) and late (N = 28) subgroups, according to gestational age (GA) at onset of clinical symptoms. Protein AnxA1 and us-CRP plasma levels were determined by ELISA and immunoturbidimetric assays, respectively. Transcript levels of AnxA1 in peripheral blood mononuclear cells (PBMC) were measured by real time RT-PCR. RESULTS: Increased levels of AnxA1 coincided with higher us-CRP levels in the plasma of PE women. Pregnant women with early PE had higher levels of AnxA1 and us-CRP than normotensive pregnant women with GA <34 weeks. No significant difference was found for AnxA1 and us-CRP, comparing late PE and normotensive pregnant women with GA ≥ 34 weeks. AnxA1 mRNA levels in PBMC were similar among the studied groups. AnxA1 was positively correlated with sTNF-R1, but not with us-CRP. CONCLUSIONS: Our data show that increased AnxA1 levels were associated with a systemic inflammatory phenotype in PE, suggesting AnxA1 deregulation in PE pathogenesis. However, more studies are needed to clarify the role of AnxA1 and other proresolving molecules in the context of the systemic inflammatory response in this intriguing disease.
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Anexina A1/sangre , Preeclampsia/sangre , Adulto , Anexina A1/genética , Proteína C-Reactiva/metabolismo , Femenino , Edad Gestacional , Humanos , Embarazo , ARN Mensajero/genética , ARN Mensajero/metabolismo , Receptores Tipo I de Factores de Necrosis Tumoral/sangre , Adulto JovenRESUMEN
Type 2 diabetes mellitus (DM2) is a metabolic disorder associated with hyperactivation of platelets, increased formation of platelet microparticles (PMPs) and oxidative stress that are related to cardiovascular complications. Acetylsalicylic acid (ASA) is an antiplatelet agent used in the prevention of atherothrombosis. The aim of this study was to evaluate the effect of ASA by means of platelet activation and oxidative profile. We collected blood samples of 81 patients with DM2 before and during ASA treatment. These samples were analyzed to determine the levels of 2,3-dinor thromboxane-B2 (2,3-dinor-TXB2), PMPs, thiobarbituric acid reactive species (TBARS) and 3-(4,5-dimethylthiazol-2yl)-2,5-diphenyltetrazolium bromide (MTT). Moreover, the relationship between the levels of 2,3-dinor-TXB2 with some clinical and laboratory variables such as glycated hemoglobin, platelet count, D dimer, low-density lipoprotein cholesterol and glycoprotein IIb/IIIa and cyclooxygenase-1 polymorphisms was evaluated. ASA intake did not change the levels of PMP, TBARS and MTT. Although a significant decrease in the levels of 2,3 dinorTXB2 (Pâ<â0.001) in patients under ASA has been observed, an equal and satisfactory response to this drug was not found. However, the presence of PIA2 allele in GPIIIa gene may be associated with a better response to ASA intake in these patients, whereas other clinical and laboratory variables showed no association with this drug use. These findings are consistent with previous reports in the literature that patients with DM2 do not benefit in an equal way from the use of ASA for primary prevention of atherothrombotic events.
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Aspirina/farmacología , Diabetes Mellitus Tipo 2/sangre , Activación Plaquetaria/efectos de los fármacos , Inhibidores de Agregación Plaquetaria/farmacología , Tromboxanos/metabolismo , Brasil , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estrés Oxidativo/efectos de los fármacosRESUMEN
INTRODUCTION: Preeclampsia (PE) is a multi-system disorder of pregnancy characterized by hypertension and proteinuria. Healthy pregnancy is associated with a controlled inflammatory process, which is exacerbated in PE in response to excessive placental stimuli. Gene expression levels can affect inflammation and immune regulation. It is known that differences in cytokine allele frequencies amongst populations may contribute to difference in the incidence of several diseases. OBJECTIVE: The aim of this study was to investigate the frequency of TNF-α, IL-6, IFN-γ and IL-10 genes polymorphisms and their relationship with the cytokines plasma levels in PE. METHODS: A total of 281 women were included in this study; 116 with severe PE, 107 normotensive pregnant and 58 non-pregnant women. Cytokine genotyping was carried out by the polymerase chain reaction. The analyzed polymorphisms were: TNF-α (-308 GâA), IL-10 (-1082 GâA), IL-6 (-174 GâC), and IFN-γ (+874 AâT). Cytokine plasma levels were measured by Cytometric Bead Array method. RESULTS: A higher frequency of the IFN-γ (+874) T/T genotype in severe PE comparing to normotensive pregnant women was found (P<0.001). TNF-α, IL-6 and IFN-γ plasma levels were higher in PE women compared to non-pregnant women (P<0.001; P<0.001; P=0.004). IL-6 and IFN-γ levels were also higher in PE women compared to normotensive pregnant (P<0.001; P=0.010). IL-10 levels were higher in normotensive pregnant women compared to PE (P<0.001). IFN-γ and IL-6 genes polymorphisms influenced the genic expression in PE and normotensive pregnant women, respectively. CONCLUSIONS: These results suggest that IFN-γ seems to play a role in PE occurrence.
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Citocinas/genética , Predisposición Genética a la Enfermedad/genética , Polimorfismo de Nucleótido Simple , Preeclampsia/genética , Adulto , Brasil , Estudios de Casos y Controles , Citocinas/sangre , Femenino , Citometría de Flujo , Frecuencia de los Genes , Genotipo , Humanos , Interferón gamma/sangre , Interferón gamma/genética , Interleucina-10/sangre , Interleucina-10/genética , Interleucina-6/sangre , Interleucina-6/genética , Preeclampsia/sangre , Preeclampsia/patología , Embarazo , Índice de Severidad de la Enfermedad , Factor de Necrosis Tumoral alfa/sangre , Factor de Necrosis Tumoral alfa/genética , Adulto JovenRESUMEN
BACKGROUND: Preeclampsia (PE) is characterized by hypertension and proteinuria. A predisposition to endothelial dysfunction, which may trigger abnormal activation of the hemostatic and/or inflammatory systems, is thought to play a crucial part in pathogenesis of PE. We investigated the relationship between hemostatic and inflammatory parameters in women with severe PE. METHODS: D-Dimer, PAI-1, IL-8, IL-6, TNF-α, and IFN-γ concentrations were measured in 59 pregnant women with severe PE (sPE), 49 normotensive pregnant and 48 non-pregnant women. RESULTS: D-Dimer and PAI-1 were higher in women with sPE compared to normotensive pregnant and non-pregnant women. IL-8, IL-6, and IFN-γ also were higher in women with sPE compared to normotensive pregnant women. However, only IL-6 and IFN-γ were higher in women with sPE compared to non-pregnant women. Moreover, D-Dimer and PAI-1 showed an elevated area under ROC curve proving to be excellent for discriminating sPE. Correlation analysis showed a weak correlation between D-Dimer and IL-8 and between PAI-1 and IFN-γ in sPE. CONCLUSION: D-Di and PAI-1 concentrations showed to be an important tool for monitoring sPE.
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Productos de Degradación de Fibrina-Fibrinógeno/análisis , Hemostasis , Inflamación/sangre , Inhibidor 1 de Activador Plasminogénico/sangre , Preeclampsia/sangre , Adulto , Biomarcadores/sangre , Citocinas/sangre , Femenino , Humanos , Preeclampsia/inmunología , Preeclampsia/patología , Embarazo , Adulto JovenRESUMEN
A partir de seis focos de atenção caracterizados pelas políticas públicas, que abrangem: o estado de proteção social e os Direitos Humanos; a saúde e a qualidade de vida; o meio ambiente; a educação; a cultura e a cidadania; o Direito, a Política e a justiça.
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Política , Política Pública , Política Ambiental , Política de SaludRESUMEN
Preeclampsia (PE) is a syndrome characterized by poor placentation and endothelial dysfunction. The diagnosis for this syndrome is based in hypertension and proteinuria presented after the 20th week of pregnancy. Despite intensive research, PE is still one of the leading causes of maternal mortality, although reliable screening tests or effective treatments of this disease have yet to be proposed. Microparticles (MPs) are small vesicles released after cell activation or apoptosis, which contain membrane proteins that are characteristic of the original parent cell. MPs have been proven to play key role in thrombosis, inflammation, and angiogenesis, as well as to mediate cell-cell communication by transferring mRNAs and microRNA from the cell of origin to target cells. Placenta-derived syncytiotrophoblast MPs are one of the most increased MPs during PE and may play an important role in the pathogenesis of this syndrome. Therefore, a better overall understanding of the role of MPs in PE may be useful for new clinical diagnoses and therapeutic approaches.
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Micropartículas Derivadas de Células/metabolismo , Preeclampsia/etiología , Femenino , Humanos , Placenta/metabolismo , Preeclampsia/metabolismo , EmbarazoRESUMEN
Although preeclampsia causes high maternal/fetal morbidity and mortality, the etiology of this multi-system disorder still remains to be elucidated. Herein, we have characterized the cytokine plasma levels in severe preeclamptic women compared to normotensive pregnant and non-pregnant women, aiming to better understand the immunological network and its clinical significance for the pathogenesis and severity of preeclampsia. A total of 219 women were selected. The study population was composed of three groups referred as severe preeclamptic, normotensive pregnant and non-pregnant women. Cytokine plasma levels were determined using commercially available kits, Cytometric Beads Array - CBA to quantify TNF-α, IFN-γ, IL-4, IL-5, IL-10, IL-1ß, IL-6, IL-8 and IL-12. Our findings demonstrated that severe preeclamptic state is associated with high levels of pro-inflammatory cytokines IL-8, IL-6, and IFN-γ (P < 0.05 for all) whereas normotensive pregnancy evolves high levels of regulatory cytokine IL-10 (P < 0.05). Moreover, an outstanding pro-inflammatory "cytokine signature" could be observed in severe preeclamptic women display, while an overall regulatory state is the hallmark for normotensive pregnancy. In summary, our data showed that elevated levels of pro-inflammatory cytokines in the maternal circulation with a deviation in the "IL-8 × IL-6" axis towards IFN-γ might drive the cytokine network in preeclamptic women towards an excessive systemic inflammatory state.
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Citocinas/sangre , Inflamación/sangre , Preeclampsia/sangre , Adolescente , Adulto , Demografía , Femenino , Citometría de Flujo , Humanos , Mediadores de Inflamación/metabolismo , Embarazo , Transducción de Señal , Adulto JovenRESUMEN
The present study aimed to evaluate microparticles (MPs) from different sources in women with severe preeclampsia (PE) compared with normotensive pregnant women and non-pregnant women. This case-control study evaluated 28 pregnant women with severe PE, 30 normotensive pregnant women, and 29 non-pregnant women. MPs from neutrophils, endothelial cells, monocytes, platelets, leukocytes, erythrocytes, and syncytiotrophoblast were evaluated using flow cytometry. A higher total number of MPs were observed in women with severe PE compared with normotensive pregnant women and non-pregnant women (P=0.004 and P=0.001, respectively). MPs derived from erythrocytes were increased in women with severe PE compared with normotensive pregnant women (P=0.002). A trend towards association was observed between platelet count and the number of MPs derived from platelets (P=0.09) in severe PE group. A positive correlation was also found between the number of endothelial cell-derived MPs and the number of platelet-derived MPs, leukocyte-derived MPs, neutrophil-derived MPs, and lymphocyte-derived MPs (P<0.05) in severe PE pregnant women. MP counts can be increased in severe PE, and erythrocyte and endothelial cell-derived MPs seem to be associated to severe PE.
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Micropartículas Derivadas de Células , Preeclampsia/sangre , Adulto , Estudios de Casos y Controles , Células Endoteliales/citología , Eritrocitos/citología , Femenino , Citometría de Flujo , Humanos , Recuento de Plaquetas , Embarazo , Índice de Severidad de la Enfermedad , Programas Informáticos , Adulto JovenRESUMEN
Hemodialysis (HD) is associated with increasing thrombotic trend. Vascular access thrombosis (VAT) increases morbidity in HD patients. The aim of this study was to evaluate ADAMTS13 and VWF plasma levels from patients undergoing HD as putative biomarkers of the hypercoagulability state, as well the association between these markers and VAT occurrence. This study included 195 patients on HD for more than 6 months. HD patients were allocated into two groups according to the occurrence or not of previous episode of VAT; HD with VAT (N = 46) and HD without VAT (N = 149). ADAMTS13 and VWF were performed by ELISA. There was no significant difference between HD patients with and without VAT for ADAMTS13 and VWF levels. However, VWF levels were higher (P < 0.001) and ADAMTS13 were lower (P < 0.001) in HD patients, comparing to the control group composed by healthy subjects without kidney disease, age and sex-matched (N = 80). Taken together our data suggest a potential role of the kidneys function compromised on ADAMTS13 synthesis or metabolism, regardless other known sources of ADAMTS13. The imbalance between ADAMTS13 and VWF levels does not explain the development of VAT in HD patients by itself, although it should contribute for the hypercoagulability state. Therefore, additional studies to identify other risk factors are warranted and essential for better management of HD patients.
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Proteínas ADAM/sangre , Diálisis Renal/efectos adversos , Trombosis/sangre , Factor de von Willebrand/metabolismo , Proteína ADAMTS13 , Adolescente , Adulto , Anciano , Biomarcadores/sangre , Ensayo de Inmunoadsorción Enzimática , Femenino , Humanos , Riñón/metabolismo , Enfermedades Renales/sangre , Enfermedades Renales/terapia , Masculino , Persona de Mediana Edad , Trombosis/etiología , Factores de TiempoRESUMEN
INTRODUCTION: Preeclampsia (PE) is a multifactorial disease characterized by high blood pressure and proteinuria after the 20th week of pregnancy. PE is associated with fibrin deposition in placental microcirculation and intrauterine fetal growth retardation. We evaluated FVIII activity, VWF and ADAMTS13 plasma levels, according to O and "non O" blood groups, in women with severe PE (sPE). METHODS: This case-control study included 140 women; 55 pregnant with sPE, 35 normotensive pregnant and 50 non-pregnant women. VWF and ADAMTS13 antigen levels were assessed by ELISA (American Diagnostica). FVIII activity was measured by automated coagulometric method (Dade Behring) and ABO blood groups phenotyping was performed by indirect technique. RESULTS: FVIII activity and VWF levels were significantly higher comparing either sPE to normotensive pregnant (P=0.01; P=0.05) and to non-pregnant women (P=0.00 in both cases) or normotensive pregnant and non-pregnant women (P=0.00 in both cases). A significant decrease in ADAMTS13 levels was observed comparing either sPE to normotensive pregnant (P=0.02) and non-pregnant women (P=0.00) or normotensive pregnant and non-pregnant women (P=0.00). FVIII activity and VWF levels were associated to O and "non O" blood groups only in non-pregnant women. CONCLUSIONS: The increase of FVIII activity and VWF levels and the decrease of ADAMTS13 in sPE are not associated to O and "non O" blood groups. These alterations in hemostatic markers in sPE largely surpass those physiologically determined by ABO blood groups influence and may have masked the effect of O and "non O" groups in this disease. A concomitant analysis of VWF levels and ADAMTS13 activity and antigenic levels will be important to clarify the imbalance between these parameters found in sPE in the present study.
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Sistema del Grupo Sanguíneo ABO , Proteínas ADAM/metabolismo , Preeclampsia/sangre , Factor de von Willebrand/metabolismo , Proteína ADAMTS13 , Femenino , Humanos , EmbarazoRESUMEN
INTRODUCTION: Normal pregnancy is associated with a local hypercoagulable state that becomes more profound in certain obstetric complications such pre-eclampsia (P-EC). Current literature on the levels of individual haemostatic factors in women with P-EC is limited and results are inconsistent. In this study we provide detailed investigation on the tissue factor (TF)-dependent pathway in women with P-EC. MATERIALS AND METHODS: Enzyme-linked immunosorbent assays (ELISA) were used to measure plasma factor (F) FVII, FVIIa, TF and tissue factor pathway inhibitor (TFPI) in healthy non-pregnant women (n = 22), normal pregnant women (n = 15), and women with P-EC (n = 20). All subjects were age matched. In addition, pregnant women were matched for gestational age, parity and were all at the third trimester. RESULTS: Plasma FVII levels were significantly higher in women with P-EC compared to the healthy non-pregnant (P<0.001) or the normal pregnant groups (P<0.001). No such significant trends were observed for plasma FVIIa, TF or TFPI levels. Plasma FVII levels can distinguish women with P-EC from healthy non-pregnant women or normal pregnant women at the third trimester, with high sensitivity (90%), specificity (80%), positive and negative predictive values (86%). CONCLUSIONS: Plasma FVII levels are significantly elevated in women with P-EC, in the absence of comparable changes in other TF-dependent pathway factors (FVIIa, TF and TFPI). We propose the use of plasma FVII as a marker for P-EC.
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Factor VII/análisis , Preeclampsia/sangre , Adulto , Biomarcadores/sangre , Estudios de Casos y Controles , Inglaterra , Ensayo de Inmunoadsorción Enzimática , Factor VIIa/análisis , Femenino , Humanos , Lipoproteínas/sangre , Valor Predictivo de las Pruebas , Embarazo , Tercer Trimestre del Embarazo , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Tromboplastina/análisis , Regulación hacia Arriba , Adulto JovenRESUMEN
BACKGROUND: Vascular access thrombosis increases morbidity in hemodialysis (HD) patients. The aim of this study was to investigate the association between HD vascular access thrombosis and mutations in the prothrombin and factor V Leiden (FV) genes and ABO blood system. METHODS: This cross-sectional study included 195 patients with end stage renal disease (ESRD) on HD for more than six months. HD patients were allocated into two groups according to the occurrence (cases, N=46) or not (controls, N=149) of previous vascular access thrombosis. FV and prothrombin gene mutations were investigated by polymerase chain reaction and ABO blood group phenotyping was performed by the indirect technique. Univariate analysis detected the variables with a trend to be associated with thrombosis and was followed by multivariate analysis to define independent predictors of vascular access thrombosis. RESULTS: FV Leiden mutation and ABO blood group were not associated with vascular access thrombosis, whereas G20210A mutation in the prothrombin gene was significantly higher in patients with vascular access thrombosis and independently associated with this complication (OR=12.0; CI 95%=1.8-83.5; p=0.012). CONCLUSIONS: G20210A mutation emerges as an important genetic factor predisposing to vascular access thrombosis. The definition of risk factors for thrombosis will certainly enable a rational approach for HD patients.