RESUMO
CONTEXT AND OBJECTIVE: Arterial thrombosis may occur consequent to hereditary thrombophilia and increased lipoprotein(a) [Lp(a)] and fibrinogen. Our aim was to study the prevalence of common thrombophilia markers in 85 consecutive cases of arterial thrombosis. DESIGN AND SETTING: A retrospective study was conducted from 85 consecutive young patients treated as outpatients or admitted due to stroke or myocardial infarction at a tertiary care hospital. METHODS: Eighty-five Indian patients (age < 45 years) presenting ischemic stroke (n = 48) or myocardial infarction (n = 37) and 50 controls were studied for seven thrombophilia markers including antithrombin (AT), factor V, protein C, protein S, activated protein C resistance (APC-R), fibrinogen and Lp(a). Functional assays for protein C, protein S, factor V and APC-R were performed using clotting-based methods. Semi-quantitative estimation of fibrinogen was done using Clauss's method and Lp(a) using immunoturbidimetry. Statistical analysis was done using the Epi Info 6 software. RESULTS: Thirty-three samples (38.8%) tested positive for one or more thrombophilia markers. The three commonest abnormalities were elevated Lp(a) (20%), fibrinogen (17.6%) and low APC-R (14.2%). Low levels of protein C, protein S and AT were present in 4.7, 9.4 and 7% of the patients, respectively. Overall, the risk factor profile was: smoking (33%), positive family history (15.3%), hyperlipidemia (7%), hypertension, diabetes mellitus and obesity (2.3% each). CONCLUSIONS: An association was found between low levels of protein C, protein S and AT and arterial thrombosis, but only elevated fibrinogen levels, smoking, positive family history and hyperlipidemia showed statistical significance.
Assuntos
Infarto do Miocárdio/sangue , Acidente Vascular Cerebral/sangue , Trombofilia/sangue , Trombose/sangue , Resistência à Proteína C Ativada/sangue , Adolescente , Adulto , Fatores Etários , Antitrombinas/sangue , Biomarcadores/sangue , Proteínas Sanguíneas/análise , Estudos de Casos e Controles , Criança , Pré-Escolar , Feminino , Humanos , Índia , Lipoproteínas/sangue , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/complicações , Valores de Referência , Estudos Retrospectivos , Fatores de Risco , Fumar/sangue , Acidente Vascular Cerebral/complicações , Centros de Atenção Terciária , Trombofilia/etiologia , Trombose/complicações , Adulto JovemRESUMO
CONTEXT AND OBJECTIVE: Arterial thrombosis may occur consequent to hereditary thrombophilia and increased lipoprotein(a) [Lp(a)] and fibrinogen. Our aim was to study the prevalence of common thrombophilia markers in 85 consecutive cases of arterial thrombosis. DESIGN AND SETTING: A retrospective study was conducted from 85 consecutive young patients treated as outpatients or admitted due to stroke or myocardial infarction at a tertiary care hospital. METHODS: Eighty-five Indian patients (age < 45 years) presenting ischemic stroke (n = 48) or myocardial infarction (n = 37) and 50 controls were studied for seven thrombophilia markers including antithrombin (AT), factor V, protein C, protein S, activated protein C resistance (APC-R), fibrinogen and Lp(a). Functional assays for protein C, protein S, factor V and APC-R were performed using clotting-based methods. Semi-quantitative estimation of fibrinogen was done using Clauss's method and Lp(a) using immunoturbidimetry. Statistical analysis was done using the Epi Info 6 software. RESULTS: Thirty-three samples (38.8%) tested positive for one or more thrombophilia markers. The three commonest abnormalities were elevated Lp(a) (20%), fibrinogen (17.6%) and low APC-R (14.2%). Low levels of protein C, protein S and AT were present in 4.7, 9.4 and 7% of the patients, respectively. Overall, the risk factor profile was: smoking (33%), positive family history (15.3%), hyperlipidemia (7%), hypertension, diabetes mellitus and obesity (2.3% each). CONCLUSIONS: An association was found between low levels of protein C, protein S and AT and arterial thrombosis, but only elevated fibrinogen levels, smoking, positive family history and hyperlipidemia showed statistical significance. .
CONTEXTO E OBJETIVO: Trombose arterial pode ocorrer em consequência de trombofilias hereditárias e de lipoproteína (a) [Lp (a)] e fibrinogênio aumentados. Nosso objetivo foi estudar a predominância de marcadores comuns da trombofilia em 85 casos consecutivos de trombose arterial. TIPO DE ESTUDO E LOCAL: Um estudo retrospectivo foi realizado sobre 85 pacientes jovens tratados consecutivamente no ambulatório ou admitidos por infarto do miocárdio ou acidente vascular cerebral (AVC) num hospital de cuidado terciário. MÉTODOS: Oitenta e cinco pacientes indianos (idade < 45 anos) que se apresentaram com AVC isquêmico (n = 48) ou infarto do miocárdio (n = 37) e 50 controles foram estudados para sete marcadores de trombofilia que incluíram antitrombina (AT), fator V, proteína C, proteína S, resistência ativada da proteína C (APC-R), fibrinogênio e Lp (a). Os ensaios funcionais da proteína C, proteína S, fator V e APC-R foram executados por métodos baseados em coagulação. A avaliação semiquantitativa do fibrinogênio foi feita pelo método de Clauss e a Lp(a) por imunoturbimetria. A análise estatística foi feita pelo software Epi Info 6. RESULTADOS: Trinta e três amostras (38.8%) foram positivas para um ou vários marcadores do trombofilia. As anomalias mais comuns foram Lp (a) (20%), fibrinogênio (17.6%) e APC-R (14.2%) elevados. Baixos níveis da proteína C, proteína S e AT foram detectados em 4.7%, 9.4% e 7% dos pacientes, respectivamente. Globalmente, os perfis dos fatores de risco foram: fumo (33%), antecedentes familiares positivos (15.3%), hiperlipidemia (7%), hipertensão, diabetes mellitus e obesidade (2.3% cada). CONCLUSÕES: Uma associação foi encontrada entre baixos níveis de proteína C, proteína S, AT e trombose arterial, ...
Assuntos
Adolescente , Adulto , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem , Infarto do Miocárdio/sangue , Acidente Vascular Cerebral/sangue , Trombofilia/sangue , Trombose/sangue , Resistência à Proteína C Ativada/sangue , Fatores Etários , Antitrombinas/sangue , Biomarcadores/sangue , Proteínas Sanguíneas/análise , Estudos de Casos e Controles , Índia , Lipoproteínas/sangue , Infarto do Miocárdio/complicações , Valores de Referência , Estudos Retrospectivos , Fatores de Risco , Fumar/sangue , Acidente Vascular Cerebral/complicações , Centros de Atenção Terciária , Trombofilia/etiologia , Trombose/complicaçõesRESUMO
CONTEXT AND OBJECTIVE: venous thrombosis occurs as a result of interaction of genetic and acquired factors including activated protein C resistance (APC-R), fibrinogen levels, antithrombin, protein C, protein S, lupus anticoagulants and anticardiolipin antibodies. This study was aimed at determining the prevalence of these common thrombophilia markers in Asian Indians with primary venous thrombosis. DESIGN AND SETTING: this was a cross-sectional study carried out in Mumbai. METHODS: samples from 78 patients with a confirmed diagnosis of venous thrombosis and 50 controls were tested. Semi-quantitative estimation (functional assays) of protein C, protein S and antithrombin was performed. Quantitative estimation of fibrinogen was done using the Clauss method. Lupus anticoagulants were screened using lupus-sensitive activated partial thromboplastin time and ß2-glycoprotein-I dependent anticardiolipin antibodies were estimated by ELISA. APC-R was measured using a clotting-based method with factor V deficient plasma and Crotalus viridis venom. Statistical analysis was performed using Epi-info (version 6). RESULTS: the popliteal vein was the most commonly involved site. Forty-four samples (56%) gave abnormal results. The commonest were elevated fibrinogen and APC-R (17.9% each), followed by low protein S (16.6%). CONCLUSIONS: this study confirms the literature findings that fibrinogen level estimation and screening for APC-R are important for the work-up on venous thrombosis patients since these, singly or in combination, may lead to a primary thrombotic episode. The frequency of the other thrombophilia markers was higher among the patients than among the controls, but without statistically significant difference.
Assuntos
Resistência à Proteína C Ativada/sangue , Fibrinogênio/análise , Veia Poplítea/patologia , Proteína S/análise , Trombofilia/diagnóstico , Trombose Venosa/complicações , Adulto , Biomarcadores/sangue , Métodos Epidemiológicos , Feminino , Humanos , Índia , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Adulto JovemRESUMO
CONTEXT AND OBJECTIVE: Venous thrombosis occurs as a result of interaction of genetic and acquired factors including activated protein C resistance (APC-R), fibrinogen levels, antithrombin, protein C, protein S, lupus anticoagulants and anticardiolipin antibodies. This study was aimed at determining the prevalence of these common thrombophilia markers in Asian Indians with primary venous thrombosis. DESIGN AND SETTING: This was a cross-sectional study carried out in Mumbai. METHODS: Samples from 78 patients with a confirmed diagnosis of venous thrombosis and 50 controls were tested. Semi-quantitative estimation (functional assays) of protein C, protein S and antithrombin was performed. Quantitative estimation of fibrinogen was done using the Clauss method. Lupus anticoagulants were screened using lupus-sensitive activated partial thromboplastin time and β2-glycoprotein-I dependent anticardiolipin antibodies were estimated by ELISA. APC-R was measured using a clotting-based method with factor V deficient plasma and Crotalus viridis venom. Statistical analysis was performed using Epi-info (version 6). RESULTS: The popliteal vein was the most commonly involved site. Forty-four samples (56 percent) gave abnormal results. The commonest were elevated fibrinogen and APC-R (17.9 percent each), followed by low protein S (16.6 percent). CONCLUSIONS: This study confirms the literature findings that fibrinogen level estimation and screening for APC-R are important for the work-up on venous thrombosis patients since these, singly or in combination, may lead to a primary thrombotic episode. The frequency of the other thrombophilia markers was higher among the patients than among the controls, but without statistically significant difference.
CONTEXTO E OBJETIVO: A trombose venosa ocorre como resultado da interação de fatores genéticos e adquiridos, incluindo resistência à proteína C ativada (APC-R), os níveis de fibrinogênio, antitrombina, proteína C, proteína S, anticoagulante lúpico e anticorpos anticardiolipina. Este estudo teve como objetivo verificar a prevalência de fatores trombofílicos frequentes em indianos com trombose venosa primária. TIPO DE ESTUDO E LOCAL: Estudo transversal analítico realizado em Mumbai. MÉTODOS: Foram testadas amostras de 78 pacientes com diagnóstico confirmado de trombose venosa e 50 controles. Foi realizada a dosagem sérica semiquantitativa (funcional) de proteína C, proteína S e antitrombina e a dosagem quantitativa de fibrinogênio (método de Clauss). Anticoagulantes lúpicos foram identificados por meio do tempo de tromboplastina parcial ativada sensível ao lúpus, e anticorpos anticardiolipina dependentes de β2-glycoproteína-I por ELISA. APC-R foi medida por método baseado em coagulação com plasma deficiente em fator V e veneno de Crotalus viridis. A análise estatística utilizou Epi-info (versão 6). RESULTADOS: A veia poplítea foi o local mais frequentemente afetado; 44 amostras (56 por cento) tiveram resultados anormais. Os achados mais frequentes foram elevação do fibrinogênio e APC-R (17,9 por cento cada), e baixa proteína S (16,6 por cento). CONCLUSÕES: Corroborando com a literatura, este estudo mostrou que a elevação do nível de fibrinogênio e a triagem para APC-R são importantes na avaliação de pacientes com trombose venosa, pois, individualmente ou em combinação, podem ter levado ao episódio trombótico primário. A frequência dos outros marcadores de trombofilia foi mais alta entre os doentes quando comparados aos controles, porém sem diferença estatisticamente significante.
Assuntos
Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem , Resistência à Proteína C Ativada/sangue , Fibrinogênio/análise , Veia Poplítea/patologia , Proteína S/análise , Trombofilia/diagnóstico , Trombose Venosa/complicações , Biomarcadores/sangue , Métodos Epidemiológicos , Índia , Fatores de RiscoRESUMO
BACKGROUND: The abnormal response to activated protein C could be the mechanism to explain the prothrombotic role of elevated coagulation factor levels. OBJECTIVE: We evaluated the effect of factor VIII, II, or X (FVIII, FII, or FX) levels on activated protein C resistance technique and its association with the resistant phenotype. MATERIALS AND METHODS: The correlation between APCR and FVIII was assessed in 36 samples, after Desmopressin infusion and the correlation between FII or FX and APCR in 15 patients with plasma levels between 100-125 U/dl. Also, the effect of the addition of purified human factors (FII, FX) to a normal plasma pool (final concentration: 100, 120, 140, 180, 220 U/dl) was estimated on the APCR technique. RESULTS: APCR values correlated with FVIII increase (r(Spearman) = 0.839; p < 0.001); APCR was abnormal (<2.4) in 9/36 samples, showing higher FVIII values in the abnormal group (VIII(abnormalAPCR) = 176.7 +/- 14.2; VIII(normalAPCR) = 103.5 +/- 8.0). APCR did not correlate with endogenous FII (r(Spearman) = 0.423) or FX (r(Spearman) = -0.169). However, the addition of human FII or FX to the normal plasma pool caused a decrease in APCR (r(SpearmanFII) = -0.843; r(SpearmanFX) = -0.958) without reaching abnormal (<2.4) results. FVIII levels may be associated with a resistant phenotype at values >153.0 U/dl, according to the linear regression analysis. Exogenous FII or FX levels greater than 120 U/dl would affect the APCR, without obtaining abnormal results. CONCLUSIONS: The data do not allow the direct association of the FII or FX increase with a defect in the protein C system in the current conditions.
Assuntos
Fator VIII/metabolismo , Fator VIII/farmacologia , Fator X/metabolismo , Fator X/farmacologia , Proteína C/farmacologia , Protrombina/farmacologia , Resistência à Proteína C Ativada/sangue , Desamino Arginina Vasopressina/farmacologia , Hemostáticos/farmacologia , Humanos , Protrombina/metabolismoRESUMO
BACKGROUND AND PURPOSE: We sought to examine ischemic stroke subtypes and prevalence of thrombophilia in Brazilian stroke patients. METHOD: A total of 130 consecutive young and 200 elderly stroke patients were studied. RESULTS: Prevalence of thrombophilia was, respectively: protein S deficiency (11.5% versus 5.5%), protein C deficiency (0.76% versus 1%), resistance to activated protein C (2.3% versus 3.5%), mutation in V Leiden factor (1.5% versus 2%), antithrombin III deficiency (0% versus 0%), lupus anticoagulant (0% versus 0.5%), anticardiolipin antibodies (3% versus 10%; P=0.01), hyperhomocysteinemia (31.5% versus 53.5%; P=0.0001), mutation of the MTHFR gene in homocigosis (10% versus 5%), and heterocigosis (27.6% versus 41.9%; P=0.01). CONCLUSIONS: Prothrombotic conditions were more frequent in stroke of undetermined cause.
Assuntos
Isquemia Encefálica/reabilitação , Reabilitação/métodos , Reabilitação do Acidente Vascular Cerebral , Trombofilia/complicações , Resistência à Proteína C Ativada/sangue , Adolescente , Adulto , Fatores Etários , Idoso , Anticorpos Anticardiolipina/química , Isquemia Encefálica/patologia , Isquemia Encefálica/terapia , Brasil , Estudos de Coortes , Fator V/genética , Feminino , Hospitais , Humanos , Hiper-Homocisteinemia/patologia , Inibidor de Coagulação do Lúpus/química , Inibidor de Coagulação do Lúpus/metabolismo , Masculino , Pessoa de Meia-Idade , Mutação , Estudos Prospectivos , Deficiência de Proteína C/sangue , Deficiência de Proteína S/sangue , Fatores de Risco , Fatores Sexuais , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/terapia , TromboseRESUMO
Antiphospholipid antibodies may interfere with the PC pathway, displaying a resistance to the activated PC (resistant phenotype). This effect was evaluated by the APCR and the ProCG systems in 36 lupus anticoagulant samples, yielding abnormal results in 47% of APCR(original), 17% of APCR(modified), and 22% of ProCG test. ProCG values correlated with APCR(original) but not with APCR(modified). Most of lupus anticoagulants affecting the PC pathway showed abnormal APCR(original) results but not abnormal ProCG values. The different behavior between both systems may be due to the heterogeneity of the antibodies or could be attributed to the fact that, in the ProCG, a PC activator is added, while the APCR employs already activated exogenous PC.
Assuntos
Anticorpos Antifosfolipídeos/farmacologia , Proteína C/metabolismo , Resistência à Proteína C Ativada/sangue , Resistência à Proteína C Ativada/genética , Feminino , Humanos , Inibidor de Coagulação do Lúpus/farmacologia , Masculino , Fenótipo , Valor Preditivo dos Testes , Proteína C/efeitos dos fármacos , Kit de Reagentes para DiagnósticoRESUMO
Uma análise da proteína C ativada e do fragmento 1 + 2 da protrombina (F1 + 2) foi realizada com o objetivo de verificar o grau de ativaçäo da cascata da coagulaçäo em situaçöes onde os sistemas da coagulaçäo e da anticoagulaçäo estäo teoricamente comprometidos. Foram estudados 20 pacientes com doenças coronarianas, notadamente, angina de peito (n=8) e infarto agudo do miocárdio (n=12), além de pacientes potencialmente em risco de desenvolver doença cardiovascular (n=17). O grupo infarto foi pareado com indivíduos sadios do ponto de vista clínico e laboratorial (grupo-controle, n=12). Somente os resultados de proteína C do grupo controle em relaçäo ao grupo de risco mostraram-se significativos. Para os demais resultados de proteína C e F1 + 2 näo foi observada diferença significativa entre os grupos. No entanto, uma correlaçäo inversa e significativa (r= -0.743; p<0.05) foi observada quando se compararam os resultados dos dois parâmetros avaliados para o grupo infarto (proteína C ativada e F1 + 2). Os resultados descritos acima sugerem um comprometimento da eficiência do mecanismo da anticoagulaçäo natural o que, provavelmente, resultaria em maior geraçäo de trombina, comprovada pela correlaçäo inversa e significativa entre os níveis plasmáticos de F1 + 2 e proteína C ativada