Influence of Blood Lipids on Global Coagulation Test Results

BACKGROUND: High levels of blood lipids have been associated with high levels of coagulation factors. We investigated whether blood lipids influence the results of global coagulation tests, including prothrombin time (PT), activated partial thromboplastin time (aPTT), and thrombin generation assay (TGA). METHODS: PT, aPTT, and TGA, along with procoagulant and anticoagulant factors, were measured in 488 normal individuals. Vitamin K status was assessed with prothrombin-induced by vitamin K absence-II (PIVKA-II). RESULTS: The procoagulant factors II, VII, IX, X, and XI and anticoagulant factors protein C and protein S showed significant correlations with triglyceride, and the procoagulant factors II, V, VII, IX, X, XI, and XII and anticoagulant factors antithrombin and protein C correlated with total cholesterol. There were no correlations of blood lipid levels with PIVKA-II levels. Subjects with high triglyceride levels (> or =200 mg/dL) showed shorter PT values than those with lower triglyceride levels. However, aPTT value was not changed in terms of blood lipid levels. In both 1 and 5 pM tissue factor-induced TGAs, subjects in the high-triglyceride or high-cholesterol groups (> or =240 mg/dL) had high levels of lag time, time-to-peak, and endogenous thrombin potential. Total cholesterol was a significant determinant of PT and TGA values. CONCLUSION: High blood lipids were related with increased coagulation activity in a normal population. Our findings are expected to help interpret the global coagulation test results in individuals with high lipid levels.

Análise da expressão gênica de proteínas associadas à coagulação sanguínea na neoplasia maligna de esôfago / Analysis of gene expression of proteins associated with blood coagulation in malignant esophageal neoplasm

Estudos recentes indicam que o fator tecidual (TF) participa no crescimento tumoral, metástase e angiogênese através de uma via independente da coagulação sanguínea. A superexpressão do TF em células tumorais contribui para o estado pró-trombótico em pacientes com câncer. Adicionalmente, uma família de receptores acoplados à proteína G, conhecidos como receptores ativados por proteases (PARs), tem sido associada à biologia do tumor. Estes receptores podem ser ativados por proteases da coagulação como a trombina, o fator VIIa (FVIIa) e o fator FXa (FXa), mediando assim a sinalização celular e podendo levar a um aumento da expressão de IL-8 em vários tipos celulares. O objetivo deste estudo foi analisar a expressão do RNAm de TF, PAR-1, PAR-2 e IL-8 em pacientes com câncer de esôfago. Amostras de tecidos foram obtidas de 35 pacientes submetidos a esofagectomia ou endoscopia em 3 hospitais das regiões Sul e Sudeste do Brasil: Hospital Universitário Pedro Ernesto (HUPE-UERJ), na cidade do Rio de Janeiro, Hospital de Clínicas (HCPA-UFRGS), na cidade de Porto Alegre - Rio Grande do Sul e o Hospital de Clínicas - Gastrocentro (HC-UNICAMP), na cidade de Campinas - São Paulo. Amostras de tecido esofágico tumoral e da mucosa normal adjacente ao tumor, foram obtidas de cada paciente e o diagnóstico foi confirmado através da análise histopatológica do tecido adjacente. O RNA total foi então extraído e analisado por transcrição reversa e reação em cadeia da polimerase (RT-PCR) e por PCR em tempo real (qPCR). Nossos resultados demonstraram um aumento significativo, nas amostras tumorais quando comparadas as amostras normais, da expressão de TF (4,2 +- 5,3, SE=0,9), PAR-1 (6,1 +- 4,7, SE=0,9) e IL-8 (18,2 +- 14,4, SE=3,9), o mesmo porém não foi encontrado para o PAR-2 (1,6 +- 0,8, SE=0,2). Nossos dados sugerem que TF, PAR-1 e IL-8 podem ter um importante papel na biologia dos tumores de esôfago. Na busca por esclarecimentos de como as proteínas analisadas...

A number of studies indicate that Tissue Factor (TF) might participate in tumor growth, metastasis and angiogenesis through a pathway that is independet of blood coagulation. TF overexpression by tumor cells contributes to a pro-thrombotic status in cancer patients. Also, a family of G protein-coupled receptors known as protease-activated receptors (PARs) has been implicated in tumor biology. These receptors may be activated by blood coagulation proteases including thrombin, FVIIa and FXa, thus eliciting cell signalling which might lead to interleukin-8 (IL-8) expression by a variety of cells. The aim of this study was to compare the expression of TF, PAR-1, PAR-2 and IL-8 mRNAs in patients with esophageal cancer. Tissue samples were obtained from 35 patients submitted to esophagectomy or endoscopy in three hospitals from south and southeast regions of Brazil: Hospital Universitário Pedro Esnesto (HUPE-UERJ), located at Rio de Janeiro, Hospital de Clínicas (HCPA-UFRGS), located at Porto Alegre, Rio Grande do Sul, and Hospital de Clínicas - Gastrocentro (HC-UNICAMP), located at Campinas, São Paulo. Tumor samples and the corresponding normal mucosa were obtained from each patient and the diagnosis was confirmed by histopathological analysis of adjacent tissues. Total RNA was extracted and further analyzed by reverse transcriptase (RT)-PCR and Real Time PCR. Our results showed a significant increased expression of TF (4,2 +- 5,3, SE=0,9), PAR-1 (6,1 +- 4,7, SE=0,9) and IL-8 (18,2 +- 14,4, SE=3,9) in tumor samples, but not of PAR-2 (1,6 +- 0,8, SE=0,2). Our data indicate that TF, PAR-1 and IL-8 might play an important role in esophageal cancer. To analyze the role of this proteins in oesophageal cancer patients, we used "in vitro" models with TE-1 cell line. Our results demonstrated that TE-1 cells express TF, PAR-1 and PAR-2 and display potent procoagulant activity. In this context, we will further investigate whether the activation of PAR receptors induces...

A Case of Acute Hepatitis with Mycoplasma pneumoniae Infection and Transient Depression of Multiple Coagulation Factors

We report a case of acute severe hepatitis with Mycoplasma pneumoniae (M. pneumoniae) infection and transient depression of multiple coagulation factors. A 5-year-old boy, previously healthy, was admitted with pneumonia. M. pneumoniae infection was confirmed by serology testing. Liver enzymes were elevated on admission without any past medical history. After treatment with azithromycin for 3 days, pneumonia improved, but the hepatitis was acutely aggravated. Partial thromboplastin time (PTT) was prolonged and depression of multiple coagulation factors developed. Liver biopsy revealed features consistent with acute hepatitis. A week later, liver enzymes were nearly normalized spontaneously. Normalization of prolonged PTT and coagulation factors were also observed several months later. This may be the first case of transient depression of multiple coagulation factors associated with M. pneumoniae infection.

Menopause, estrogens, and endothelial dysfunction: current concepts

Menopause is defined as the permanent cessation of menses. Cardiovascular disease is the leading cause of death among postmenopausal women in developed countries. The disparity between the incidence of cardiovascular disease among women in pre- and postmenopause has been ascribed to the actions of endogenous estrogen on the cardiovascular system and, particularly, on the vascular endothelium. The endothelium plays an important role in cardiovascular homeostasis, either through the vascular tonus and its regulation, or through coagulation and the inflammatory response. Endothelial dysfunction is implicated in the genesis of atherosclerosis and other chronic disorders, such as diabetes mellitus and hypertension. The pharmacological use of estrogen exerts influence on the circulating levels of markers of vascular tonus, and inflammation, as well as prothrombotic, and fibrinolytic markers, but the impact of these changes on the atherosclerotic disease is still uncertain.

A menopausa é definida como a cessação permanente das menstruações. A doença cardiovascular é a principal causa de mortalidade em mulheres na pós- menopausa, em países desenvolvidos. A disparidade entre a incidência de doença cardiovascular entre mulheres na pré e pós menopausa tem sido atribuída a ações do estrogênio endógeno sobre o sistema cardiovascular e, em especial, sobre a função do endotélio vascular. O endotélio tem importante papel na homestase cardiovascular, seja no controle do tônus e permeabilidade vascular, ou da coagulação e resposta inflamatória. A disfunção endotelial está implicada na gênese da aterosclerose e de outras doenças crônicas, como diabete melito e hipertensão arterial. O uso farmacológico de estrogênio exerce influência sobre concentrações circulantes de marcadores do tônus vascular, inflamatórios, pró-trombóticos e fibrinolíticos, porém o impacto destas alterações sobre a doença aterosclerótica ainda não está determinado.

Plasma Level of IL-6 and Its Relationship to Procoagulant and Fibrinolytic Markers in Acute Ischemic Stroke

Procoagulant or impaired fibrinolytic states as well as inflammatory reactions mediated by cytokines are likely involved in the pathogenesis of acute ischemic stroke. We examined the potential relationship between interleukin 6 (IL-6) and hemostatic markers. The procoagulant and fibrinolytic states were assessed in 46 patients with acute stroke by measuring plasma levels of plasminogen activator inhibitor-1 (PAI-1), thrombin-antithrombin complex (TAT), and plasminogen-antiplasmin complex (PAP). Circulating IL-6 levels were measured using ELISA (Quantikine, R and D systems, MN, USA). Circulating IL-6 (mean, 26.5 pg/mL) and PAI-1 (mean, 19.9 ng/mL) levels were higher in patients with acute stroke than in healthy subjects (mean, 3.0 pg/mL, 10.4 ng/mL, respectively). TAT levels were statistically different according to the etiologic subtypes of stroke (atherogenic, 2.5 ng/mL; lacunar 3.2 ng/mL; cardiogenic 9.9 ng/mL, p = 0.021). Neither procoagulant levels nor fibrinolytic markers significantly correlated with circulating IL-6 levels. Our findings suggest that elevated proinflammatory cytokines during the initial hours of ischemic stroke may be an independent pathogenic factor or a consequence of the thrombotic event with no relationship to the procoagulant or fibrinolytic states.

Avaliaçäo de coagulaçäo, fibrinólise e proteína C em pacientes de risco e com doenças coronarianas / Evaluation of coagulation, fibrinolysis and protein C in risk patients and patients presenting coronarian diseases

A hemostasia é resultante do equilíbrio entre pró-coagulantes e anticoagulantes, envolvendo vasos, plaquetas, proteínas da coagulaçäo e da fibrinólise e anticoagulantes naturais. Todos estes componentes estäo inter-relacionados, constituindo os sistemas de coagulaçäo, anticoagulaçäo e fibrinólise. Muitos fatores, genéticos ou adquiridos, podem contribuir para romper este equilíbrio, levando a estados de hipo ou hipercoagulabilidade. Em doenças coronarianas como a angina e o infarto, há uma maior ativaçäo das plaquetas e das proteínas da coagulaçäo, favorecendo a formaçäo de trombos. Na tentativa de restaurar a hemostasia, ocorre a intervençäo do sistema fibrinolítico, o qual promove a lise do coágulo e desobstrui o vaso. Neste trabalho foram avaliados os mecanismos da coagulaçäo e da fibrinólise e a proteína C, um anticoagulante natural. 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 clinicolaboratorial (grupo-controle, n = 12). Os resultados revelaram uma diferença significativa nos níveis de fibrinogênio nos grupos de angina e infarto quando comparados ao grupo-controle. Níveis de proteína C ativada também mostraram diferença significativa entre os grupos de risco e infarto. Os demais parâmetros hemostáticos avaliados näo diferiram significativamente entre os grupos estudados, porém foi observada uma tendência à hipercoagulabilidade nos grupos de pacientes quando comparados ao grupo-controle

Haemostatic changes in children with cyanotic and acyanotic congenital heart disease.

This study was undertaken to screen children with congenital heart disease for coagulation abnormalities and to compare the groups of cyanotic and acyanotic children with congenital heart disease with respect to abnormalities of the coagulation system. Following investigations were done in all the patients: complete blood count, erythrocyte sedimentation rate, peripheral smear examination, bleeding time, prothrombin time, activated partial thromboplastin time, assay of fibrinogen, D-dimer, factors VII and VIII and antithrombin III. Red cell indices were determined in 12 control, 12 acyanotic and 20 cyanotic children. Twenty-five patients each, with echocardiographically proven cyanotic and acyanotic congenital heart disease under 12 years of age constituted the study group; as many children of the same age group were included as the control group. The results showed isolated abnormalities of laboratory tests with equal frequency (28%) in acyanotic and cyanotic groups but coexisting abnormalities of more than one test were seen in significantly larger number of cyanotic children (5/25 and 16/25, respectively). A significant association was noted between thrombocytopenia and a high haematocrit in cyanotic patients. It is concluded that laboratory abnormalities of tests of haemostasis are more common in cyanotic congenital heart disease patients. The patterns of laboratory abnormalities suggest a chronic compensated disseminated intravascular coagulation at a subclinical level, reduced synthesis of clotting factors and/or deranged platelet aggregation in different subgroups of patients.

Nutritional properties of trans fatty acids.

The role of trans fatty acids (TFA) present in partially hydrogenated fats widely consumed in food and their link with coronary heart disease has been examined in this review. Most of the studies carried out have been on the effects of TFA on blood-lipid profile. The perceived effects of TFA intake depend on the fat or oil with which they are compared and appears to be in between that of dietary saturated fats and monounsaturated fatty acids. When compared to saturated fat, TFA intake shows lower levels of total and LDL-cholesterol in blood. But when both TFA and saturated fatty acids are compared with cis fatty acids or native unhydrogenated oil, increase in total and LDL-cholesterol are noted. The effects of TFA on HDL-cholesterol and Lp(a) are not clearly established. The undesirable effects of TFA can be overcome by inclusion of essential fatty acids at a minimum of 2 energy per cent level in the diet. The link between trans fatty acid intake and coronary heart disease (CHD) are not unequivocally established.

Pregnancy induced hypertension: changes in coagulation profile of newborns.

Coagulation parameters and platelet count were studied in 30 neonates of mothers with pregnancy induced hypertension (PIH). 30 neonates born to normotensive mothers were taken as controls. The test group was further subdivided as neonates born to mothers with gestational hypertension, pre-eclamptic toxemia and eclampsia. The values of Prothrombin Time, Partial Thromboplastin Time with Kaolin, Thrombin Time, Fibrinogen Degradation Products were significantly raised and Fibrinogen and Platelet count were reduced significantly in both term and preterm test groups as compared to controls. The derangement in coagulation parameters was more marked with increasing severity of PIH.

Problems of diagnosis of disseminated intravascular coagulation (DIC).

Acute generalized intravascular coagulation is regularly associated with fibrinolysis. Evidence of the clotting process includes thrombocytopenia, hypofibrinogenemia, prolongation of the prothrombin time (deficiency of factor V and fibrinogen) and of the partial thromboplastin time (factor VIII is also deficient). Evidence of fibrinolysis is elevation of fibrinolytic split products (FSP or FDP). A positive protamine gel results from both coagulation and fibrinolysis.