RESUMO
Since insulin resistance is accepted to be a common feature of polycystic ovary syndrome (PCOS), the exact molecular mechanism(s) involved in glucose and lipid metabolism have been under investigation in the syndrome. Recently, two novel adipokines, namely visfatin and retinol-binding protein 4 (RBP4), have been suggested to play a role in insulin resistance and diabetes. This study sought to determine whether plasma concentrations of visfatin and RBP4 are altered in PCOS by comparing a total of 27 lean, normal glucose-tolerant PCOS patients with 19 age- and body mass index-matched healthy controls. The mean plasma visfatin concentrations were higher in PCOS patients than those in healthy subjects (37.9+/-18.2 versus 19.8+/-17.5, P<0.01), while RBP4 concentrations were similar between the two. Both adipokines were correlated with each other in the whole (r=0.50, P<0.01) and in PCOS (r=0.52, P<0.01) groups but not in controls. The results suggest that lean, glucose-tolerant women with PCOS have increased circulating visfatin and unaltered RBP4 concentrations compared with healthy lean women. In order to clarify overlapping effects and their potential contribution to the pathophysiology of PCOS, further studies are needed.
Assuntos
Nicotinamida Fosforribosiltransferase/sangue , Síndrome do Ovário Policístico/sangue , Proteínas Plasmáticas de Ligação ao Retinol/metabolismo , Adulto , Estudos de Casos e Controles , Estudos Transversais , Feminino , Humanos , Resistência à Insulina/fisiologia , Obesidade , Síndrome do Ovário Policístico/fisiopatologia , MagrezaRESUMO
Thrombopoiesis is regulated by a variety of cytokines. Intracellular adhesion molecules are inducible cell-surface glycoproteins that belong to the immunoglobulin superfamily. Cytokines, endothelium and adhesive molecules represent the point of crosstalk in normal and pathological hematopoiesis. With the hypothesis that circulating intracellular adhesion molecule-1 (ICAM-1) and lymhocyte adhesion molecule-1 (L-selectin) concentrations could be changed based on pathological thrombopoiesis resulting in quantitative platelet disorders, we evaluated ICAM-1 and L-selectin levels in patients with thrombocytosis, thrombocytopenia and healthy controls. The L-selectin levels were found to be significantly higher in the thrombocytopenia group compared to the control group. ICAM-1 levels were found to be significantly higher in both thrombocytopenia and thrombocytosis groups compared to control group. Our study corroborates our original hypothesis implying the roles of adhesion molecules in the challenging status of pathological thrombopoiesis.
Assuntos
Molécula 1 de Adesão Intercelular/metabolismo , Selectina L/metabolismo , Trombocitopenia/metabolismo , Trombocitose/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Citocinas/metabolismo , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Transdução de Sinais/fisiologia , Adulto JovemRESUMO
Cytokines like interleukin (IL)-6 and IL-1beta are both implicated in multiple myeloma (MM) pathogenesis and megakaryopoiesis. The dynamic interaction between thrombopoiesis and thrombopoietic cytokines in MM may affect platelet (PLT) counts. Sixty-eight patients with MM (30 female, 38 male; median age 58 (40-79), 38 newly diagnosed, 15 in plateau, and 15 relapse and/or refractory patients) and 21 controls were included in the study. Plasma levels of thrombopoietin (TPO), IL-1beta, IL-11 and IL-6 were measured by ELISA. PLT counts were not different between the control group and MM patients with various disease stages and activity. IL-6 and TPO levels were higher in MM patients than healthy subjects (p < 0.001). PLT counts were inversely correlated with TPO (r = -0.566; p < 0.001) and positively correlated with IL-6 (r = 0.263; p = 0.04) levels in MM patients. TPO and IL-6 levels were significantly correlated (r = 0.305; p < 0.001). Disease activity has no effect on plasma cytokine levels. TPO levels were higher in stage III than stage I (p = 0.05) and stage II (p = 0.03) patients in newly diagnosed MM. High TPO levels induced by IL-6 may sustain normal PLT counts despite bone marrow infiltration by plasma cells and decreased PLT half-life.
Assuntos
Citocinas/sangue , Mieloma Múltiplo/sangue , Contagem de Plaquetas , Trombopoese/fisiologia , Adulto , Idoso , Feminino , Humanos , Interleucina-11/sangue , Interleucina-1beta/sangue , Interleucina-6/sangue , Masculino , Megacariócitos , Pessoa de Meia-Idade , Mieloma Múltiplo/fisiopatologia , Trombopoetina/sangueRESUMO
Patients with end-stage renal disease have a very high prevalence and extent of arterial calcification. A number of studies suggest that similar pathophysiologic mechanisms are responsible for development and progression of calcification of atherosclerotic plaque and bone formation. Fetuin-A is a potent calcification inhibitor and is expressed in bone, with not-yet well-defined functions. The aim of this study was to investigate the relation between bone mineral densitometry parameters, coronary artery calcification, and serum fetuin-A levels. In a cross-sectional design, we included 72 maintenance hemodialysis (HD) patients and 30 age- and gender-matched healthy controls. Serum fetuin-A levels were studied both in maintenance HD patients and healthy controls. Maintenance HD patients had radius, hip, and lumbar spine bone mineral density (BMD) assessed by dual-energy X-ray absorptiometry and coronary artery calcification score (CACS) measured by electron-beam computed tomography. The associations between site-specific BMD parameters, CACS, and serum fetuin-A levels were studied in maintenance HD patients. CACS, mass, and volume of plaques in coronary arteries were significantly higher in patients with a T-score below -2.5 than above in the proximal region of the radius, neck and trochanter of the femur, and the lumbar spine. Mean serum fetuin-A concentration was 0.636 +/- 0.118 g/L in maintenance HD patients and it was less than healthy controls (0.829 +/- 0.100 g/L, P < 0.0001). CACS, mass, and volume of plaques in coronary arteries correlated significantly with the serum fetuin-A levels. Moreover, significant positive correlations were shown between the serum fetuin-A levels, BMD values, and T-scores of proximal radius, neck, and trochanter of the femur, but not with the lumbar spine. The present study demonstrates an association between serum fetuin-A levels, coronary artery calcification, and bone mineral densities--except for the lumbar spine, in maintenance HD patients. However, the results should be interpreted with caution because of the cross-sectional design of the study.
Assuntos
Proteínas Sanguíneas/análise , Densidade Óssea , Calcinose/etiologia , Doença da Artéria Coronariana/etiologia , Falência Renal Crônica/terapia , Diálise Renal , Absorciometria de Fóton , Adulto , Idoso , Biomarcadores/sangue , Calcinose/sangue , Calcinose/diagnóstico por imagem , Estudos de Casos e Controles , Doença da Artéria Coronariana/sangue , Doença da Artéria Coronariana/diagnóstico por imagem , Estudos Transversais , Feminino , Articulação do Quadril/diagnóstico por imagem , Humanos , Falência Renal Crônica/sangue , Falência Renal Crônica/complicações , Falência Renal Crônica/diagnóstico por imagem , Vértebras Lombares/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Rádio (Anatomia)/diagnóstico por imagem , Medição de Risco , Fatores de Risco , Índice de Gravidade de Doença , Tomografia Computadorizada por Raios X , alfa-2-Glicoproteína-HSRESUMO
AIM: Ankaferd comprises a mixture of Thymus vulgaris, Glycyrrhiza glabra, Vitis vinifera, Alpinia officinarum and Urtica dioica. Ankaferd Blood Stopper (ABS) has been approved in the management of bleedings. This study aimed to evaluate in vivo hemostatic effect of ABS in rats pretreated with warfarin. MATERIALS AND METHODS: Wistar rats (210-270 g) were treated either with warfarin (2 mg/kg) or vehicle (0.9% NaCl) orally before bilateral hind leg amputation. ABS was administered topically to one of the amputed legs. The duration of bleeding and the amount of bleeding were measured to evaluate the hemostatic effect of ABS. RESULTS: Topical ABS administration to amputed leg shortened the duration of bleeding markedly in both untreated and warfarin-treated rats by 31.9% [1.42 min (95% CI: 0.35-2.49)] and 43.5% [5.12 min (95% CI: 2.16-8.07)] respectively. The amount of bleeding in ABS-administered amputed leg showed a decrease by 53.8% in warfarin-treated group. CONCLUSIONS: ABS has in vivo hemostatic actions that may provide a therapeutic potential for the management of patients with deficient primary hemostasis in clinical medicine.
Assuntos
Perda Sanguínea Cirúrgica/prevenção & controle , Hemorragia/prevenção & controle , Hemostasia/efeitos dos fármacos , Hemostáticos/farmacologia , Extratos Vegetais/farmacologia , Administração Tópica , Amputação Cirúrgica , Animais , Modelos Animais de Doenças , Feminino , Hemorragia/sangue , Hemorragia/induzido quimicamente , Hemostáticos/administração & dosagem , Membro Posterior/cirurgia , Masculino , Extratos Vegetais/administração & dosagem , Ratos , Ratos Wistar , Fatores de Tempo , VarfarinaRESUMO
OBJECTIVE: The purpose of this study was to show the hemostatic effect of spray, solution and tampon forms of Ankaferd Blood Stopper (ABS), a unique medicinal plant extract historically used as a hemostatic agent in Turkish folklore medicine, in a porcine bleeding model. MATERIALS AND METHODS: Two 1-year-old pigs were used as bleeding models for superficial and deep skin lacerations, grade II liver and spleen injuries, grade II saphenous vein injury and grade IV saphenous artery injury. Spray, solution or tampon forms of ABS were applied after continuing bleeding was confirmed. The primary outcome was time to hemostasis. Volume of blood loss was not measured. The pigs were euthanized at the end of the experiment. RESULTS: Spray or direct application of ABS solution resulted in instant control of bleeding in superficial and deep skin lacerations as well as puncture wounds of the liver. A 40-second application of ABS tampon was sufficient to stop bleeding of skin lacerations, while 1.5- and 3.5-min applications were used to control hemorrhage from the saphenous vein and artery, respectively. No rebleeding was observed once hemostasis was achieved. However, repeated applications of ABS solution and tampon were only temporarily effective in the hemostasis of spleen injury. CONCLUSIONS: The data showed that ABS was an effective hemostatic agent for superficial and deep skin lacerations and minor/moderate trauma injuries in a porcine bleeding model.
Assuntos
Hemorragia/tratamento farmacológico , Hemostasia/efeitos dos fármacos , Hemostáticos/administração & dosagem , Lacerações/tratamento farmacológico , Extratos Vegetais/administração & dosagem , Ferimentos Penetrantes/tratamento farmacológico , Administração Cutânea , Animais , Artérias/lesões , Modelos Animais de Doenças , Eutanásia Animal , Folclore , Hemorragia/sangue , Técnicas Hemostáticas , Fígado/lesões , Veia Safena/lesões , Baço/lesões , Suínos , Tampões Cirúrgicos , TurquiaRESUMO
BACKGROUND/AIMS: Experimental studies suggest an enhanced endothelial and platelet nitric oxide (NO) generation after statin treatment, possibly due to increased endothelial NO synthase (eNOS) activity and protein levels. In parallel with experimental research, statins were shown to increase the forearm blood flow independently of serum cholesterol in humans. However, it was not possible to correlate blood flow changes with eNOS levels in these studies due to limitations in obtaining arterial samples. Hence, we investigated changes in eNOS activity, mRNA and protein levels after statin treatment in human platelets, which are readily accessible unlike arteries. METHODS: In vitro bleeding times were measured in 22 patients by stimulating platelets with collagen-epinephrine or collagen-ADP. To assess platelet eNOS activity, the bleeding times were also determined after incubating platelets with L-arginine. The measurements were repeated following 14 days of pravastatin (40 mg/day) treatment. Platelet-rich plasma was collected before and after statin treatment to evaluate eNOS mRNA (semiquantitative RT-PCR) and protein levels (Western blotting). RESULTS: The basal bleeding time was prolonged by 24 +/- 3% (mean +/- SE) when the samples were incubated with 500 microM of L-arginine. The NOS inhibitor L-N(5)-(I-iminoethyl)ornithine reversed this effect, suggesting that it was mediated by NO. After statin treatment, the NO-mediated prolongation of the bleeding time with 500 microM of L-arginine was significantly potentiated (to 44 +/- 10%). Despite enhanced eNOS activity, there was no significant change in platelet eNOS mRNA and protein levels after statin treatment. CONCLUSION: These data demonstrate that platelet eNOS activity is potentiated after statin treatment in humans in parallel with experimental studies.
Assuntos
Plaquetas/efeitos dos fármacos , Isquemia Encefálica/complicações , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Óxido Nítrico Sintase Tipo III/metabolismo , Óxido Nítrico/metabolismo , Agregação Plaquetária/efeitos dos fármacos , Pravastatina/uso terapêutico , Acidente Vascular Cerebral/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Arginina/metabolismo , Tempo de Sangramento , Plaquetas/enzimologia , Isquemia Encefálica/sangue , Isquemia Encefálica/tratamento farmacológico , Inibidores Enzimáticos/farmacologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Óxido Nítrico Sintase Tipo III/antagonistas & inibidores , Óxido Nítrico Sintase Tipo III/genética , Ornitina/análogos & derivados , Ornitina/farmacologia , RNA Mensageiro/metabolismo , Acidente Vascular Cerebral/sangue , Acidente Vascular Cerebral/etiologia , Resultado do TratamentoRESUMO
OBJECTIVE: Meconium-stained amniotic fluid (MSAF) is thought to be a sign of fetal hypoxia, which causes activation of coagulation and inhibition of fibrinolysis. Inflammation is also seen in MSAF. On the other hand, thrombin activatable fibrinolysis inhibitor (TAFI) is an inhibitor of fibrinolysis and a regulator of vascular inflammation. For this reason, in this study we aimed to evaluate the relation between hypoxia, fibrinolysis, and inflammation by determining the levels of TAFI activity (TAFIa) in MSAF where inflammation was also thought to have a role in the pathogenesis. METHODS: The MSAF group consisted of 22 neonates; 20 neonates served as the control group. Plasma TAFIa levels were evaluated in all neonates in the first six hours of life. RESULTS: TAFIa levels were significantly higher in the MSAF group when compared with the control group and the levels correlated negatively with cord blood pH levels. CONCLUSIONS: Increased TAFIa levels in neonates with MSAF might be due to hypoxia. Inflammation observed in MSAF may also play an additional role in increased TAFIa expression. Although no clinical complication that can be attributed to this increase was seen, one should be alert to the complications of depressed fibrinolysis that might be observed in these neonates.
Assuntos
Líquido Amniótico , Carboxipeptidase B2/sangue , Mecônio , Feminino , Sangue Fetal/química , Idade Gestacional , Humanos , Concentração de Íons de Hidrogênio , Hipóxia/sangue , Recém-Nascido , Inflamação/sangue , MasculinoRESUMO
Quantitative platelet disorders (i.e., thrombocytosis or thrombocytopenia) may also be associated with qualitative platelet alterations. Clonal thrombocythemia (CT), reactive thrombocytosis (RT), immune thrombocytopenic purpura (ITP), and thrombocytopenia of aplastic pancytopenia (AA) or infiltrative bone marrow disorders represent the major classes of pathological thrombopoiesis. Glycoprotein V may serve as an in vivo marker of platelet activation in thrombotic and hemorrhagic states. The aim of this study was to assess circulating plasma soluble platelet glycoprotein V (sGPV) concentrations in distinct disease states of pathological thrombopoiesis. The whole study group comprised 20 patients with thrombocytopenia, 32 patients with thrombocytosis and 14 healthy adults as the control group. sGPV was significantly increased in the group of thrombocytosis patients in comparison to the thrombocytopenic group and the healthy control groups. When sGPV levels were corrected according to platelet number (sGPV/tr), this ratio was very high in patients with thrombocytopenia compared to patients with thrombocytosis and the control group. Our results suggest that there is an ongoing platelet activation associated with thrombocytosis regardless of its origin is either CT or RT. Therefore, glycoprotein V system may serve to activate residual platelets in thrombocytopenia regardless of its origin is either ITP or AA.
Assuntos
Complexo Glicoproteico GPIb-IX de Plaquetas/análise , Trombocitopenia/sangue , Trombocitose/sangue , Adulto , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , SolubilidadeRESUMO
BACKGROUND: Strontium ranelate offers significant clinical benefits in terms of efficacy, tolerability, and ease of administration in the treatment of postmenopausal osteoporosis. However, there are some data revealing an association between strontium ranelate treatment and increased incidence of venous thromboembolism (VTE), suggesting possible adverse prothrombotic effects of the drug. OBJECTIVE: To assess the effect of strontium ranelate treatment on primary hemostasis, secondary hemostasis, and the natural anticoagulant defense system, together with prothrombotic markers, in elderly women with osteoporosis. METHODS: This study was designed in a prospective manner. Thirty-five elderly women diagnosed with osteoporosis were included. During a 2 month treatment period, participants received strontium ranelate 2 g. Platelet Function Analyzer-100 (PFA-100) in vitro bleeding time was performed to depict primary hemostasis. Secondary hemostatic parameters including prothrombin time, international normalized ratio, activated partial thromboplastin time, anti-cardiolipine immunoglobulin (Ig) M and IgG, antiphospholipid IgM and IgG, protein C, protein S, antithrombin III, lupus anticoagulant, fibrinogen, thrombin, activated protein C resistance, and plasma levels of d-dimer were assessed. These parameters were tested before and after 2 month treatment with strontium ranelate. RESULTS: Mean +/- SD age of the patients was 72.82 +/- 5.69 years. After 60 days of treatment, there was no statistically significant prolongation in PFA-100 in vitro bleeding time and no statistically significant change in the critical hemostatic parameters in patients receiving strontium ranelate that led to discontinuation of the treatment. None of the subjects developed clinical VTE during the 2 month period of strontium ranelate treatment. CONCLUSIONS: The hemostatic safety of strontium ranelate in the elderly population with osteoporosis was shown over 2 months of treatment; however, its long-term hemostatic safety should be evaluated further.
Assuntos
Hemostáticos/uso terapêutico , Compostos Organometálicos/uso terapêutico , Osteoporose/tratamento farmacológico , Tiofenos/uso terapêutico , Idoso , Tempo de Sangramento , Feminino , Hemostáticos/efeitos adversos , Humanos , Compostos Organometálicos/efeitos adversos , Osteoporose/sangue , Estudos Prospectivos , Tiofenos/efeitos adversos , Fatores de TempoRESUMO
In this study we aimed to evaluate the relationship between serum granulocyte colony stimulating factor (G-CSF) levels and absolute neutrophil counts (ANC) in infants of preeclamptic mothers. The study group consisted of 31 infants of preeclamptic mothers while the control group consisted of 24 gestational age-adjusted infants of normotensive mothers. G-CSF levels were determined by enzyme-linked immunosorbent assay (ELISA). The mean G-CSF level was 981.8 +/- 1682.5 (25.7-5924) pg/ml in the study group and 770.8 +/- 1779 (18-8526) pg/ml in control group (p > 0.05). There was no correlation between G-CSF levels and absolute or total neutrophil counts on the 1st, 2nd and 7th days in infants of preeclamptic mothers. There were positive correlations between G-CSF levels and ANC on the 1st and 7th days of life in infants of normotensive mothers. Neutropenia developed in 42.3% of the study group and in 21.7% of the control group on the 1st day of life (p > 0.05). On the 2nd day, neutropenia was observed in 61.5% of the study group and 26.1% of the control group (p = 0.013). Serum G-CSF levels were not low in neutropenic babies of preeclamptic mothers. In contrast, higher G-CSF levels in neutropenic infants suggest impaired G-CSF response in infants of preeclamptic mothers.
Assuntos
Fator Estimulador de Colônias de Granulócitos/sangue , Fator Estimulador de Colônias de Granulócitos e Macrófagos/sangue , Recém-Nascido de muito Baixo Peso/sangue , Neutropenia/sangue , Pré-Eclâmpsia/sangue , Ensaio de Imunoadsorção Enzimática , Feminino , Fator Estimulador de Colônias de Granulócitos/deficiência , Humanos , Recém-Nascido , Masculino , GravidezRESUMO
Although the severity of valvular calcification is an important prognostic indicator, the cellular mechanisms of the calcification process are unknown. Osteopontin modulates inflammation and biomineralization, and increased osteopontin expression has been demonstrated in calcified degenerative or rheumatic cardiac valves. The present study evaluated soluble plasma osteopontin in 32 patients with echocardiographically determined rheumatic mitral stenosis and compared the results to those of a control group of 22 healthy patients. Patients were evaluated with routine echocardiographic techniques, Wilkins scoring, and 2-dimensional echocardiographic calcium scoring. Patients with rheumatic involvement other than in the mitral valve were excluded. Plasma osteopontin and high-sensitivity C-reactive protein levels in patients with mitral stenosis were significantly higher those of the control group (p = 0.006 and p = 0.0001, respectively). A significant correlation was found between plasma osteopontin levels and the severity of mitral valve calcification (p = 0.003) and also between high-sensitivity C-reactive protein levels and Wilkins score (p = 0.009). There was a stepwise and statistically significant increase in soluble plasma osteopontin levels in association with the severity of mitral valve calcification. In conclusion, increased osteopontin levels were correlated with the severity of mitral valve calcification in patients with rheumatic mitral stenosis, suggesting an important role of osteopontin in the modulation of valvular calcification. Elevated levels of high-sensitivity C-reactive protein concentrations suggest the presence of ongoing inflammation in those patients.
Assuntos
Calcinose/patologia , Valva Mitral/patologia , Cardiopatia Reumática/sangue , Sialoglicoproteínas/sangue , Adulto , Biomarcadores/sangue , Proteína C-Reativa/análise , Calcinose/diagnóstico por imagem , Ecocardiografia , Feminino , Humanos , Masculino , Valva Mitral/diagnóstico por imagem , Osteopontina , Cardiopatia Reumática/complicações , Cardiopatia Reumática/diagnóstico por imagem , Cardiopatia Reumática/patologiaRESUMO
Hypofibrinolysis is a state that is commonly observed in type 2 diabetic patients, a finding also possibly related to obesity and insulin resistance. There is little information, however, regarding the status of fibrinolytic system in Type 1 diabetes, in particular as reflected by thrombin-activatable fibrinolysis inhibitor (TAFI) activity and global fibrinolytic capacity (GFC). To provide information in this respect, 30 Type 1 diabetic patients (median age=16) and 28 healthy controls (median age=14) were enrolled in this study. The median duration of diabetes was 7 years, and median HbA(1c) was 8.85% (range: 5.5-11.9%) in the diabetic group. None of the patients had macrovascular complications. Microvascular complications were present in a total of eight patients (nephropathy: n=5; retinopathy: n=3). A comparison of the TAFI activity between the patient (median 84.9, range: 71.5-103.3%) and the control groups (median=83.3, range: 63.7-97.4%) yielded no statistically significant difference (P=.950). Similarly, GFC was comparable between the two groups (median=8.22, range: 0.72-22.38 microg/ml, and median=13.32, range: 3.0-23.22 microg/ml, respectively, in the diabetic and control groups, P=.086). TAFI activity did not significantly correlate with age, albumin excretion, fasting plasma glucose, HbA(1c), D-dimer, and fibrinogen by Spearman rank correlation test. There was as a significant inverse correlation between GFC and TAFI activity (r=-.414, P=.006). Contrary to the previous observations in Type 2 diabetes, our data suggest that fibrinolytic activity is not adversely affected by Type 1 diabetes, and it has no relationship with the degree of metabolic control.
Assuntos
Carboxipeptidase B2/sangue , Diabetes Mellitus Tipo 1/fisiopatologia , Fibrinólise/fisiologia , Adolescente , Adulto , Glicemia/análise , Criança , Diabetes Mellitus Tipo 1/sangue , Feminino , Humanos , MasculinoRESUMO
The aim of this study was to compare fibrinolysis in normal pregnancy and pre-eclampsia using individual markers of thrombosis and fibrinolysis with the contribution of a new parameter, global fibrinolytic capacity. Coagulation was determined with thrombin-antithrombin complex and prothrombin fragment 1+2 (F 1+2) and fibrinolysis markers. Tissue plasminogen activator, plasminogen activator inhibitor-1 and global fibrinolytic capacity were determined in 14 normal pregnancies and 29 women with pre-eclampsia. global fibrinolytic capacity was also determined in 14 age-matched healthy women. The Mann-Whitney U test and Pearson correlation test were used for statistical analysis. Thrombin-antithrombin complex, prothrombin fragment 1+2 levels, and global fibrinolytic capacity levels in pre-eclamptic women were significantly higher than in women with normal pregnancies (P < 0.05). Tissue plasminogen activator, plasminogen activator inhibitor-1 levels were also significantly higher in the pre-eclampsia group (P < 0.001 and P < 0.05 respectively). No significant correlation was found between global fibrinolytic capacity and thrombin-antithrombin complex, prothrombin fragment 1+2 levels, tissue plasminogen activator or plasminogen activator inhibitor-1 activity. Our results suggest that both thrombin formation and fibrinolysis are increased in pre-eclampsia compared with normal pregnancy. The increased global fibrinolytic capacity indicates that fibrinolysis remains preserved in pre-eclampsia. We suggest that global fibrinolytic capacity may be a useful parameter for accurately measuring in-vivo fibrinolysis globally, instead of with single parameters which may overlook the complex interactions between coagulation and fibrinolytic systems.
Assuntos
Fibrinólise/fisiologia , Pré-Eclâmpsia/sangue , Adulto , Feminino , Humanos , Fragmentos de Peptídeos/sangue , Inibidor 1 de Ativador de Plasminogênio/sangue , Pré-Eclâmpsia/fisiopatologia , Gravidez , Precursores de Proteínas/sangue , Protrombina , Ativador de Plasminogênio Tecidual/sangueRESUMO
Clinical and epidemiologic observations have led to the concept of a procoagulant state in type 2 diabetes. This study aimed to determine the coagulation status in type 2 diabetic patients using rotation thromboelastography (ROTEM), which measures the interactive dynamic coagulation process. For this purpose, 51 (30 women, 21 men) type 2 diabetic patients (mean age, 56.1 years) and 40 age-matched, sex-matched and body-mass-index-matched healthy individuals were enrolled. Twenty-seven of the diabetic group had diabetic vascular complications. ROTEM using different activators for the intrinsic and extrinsic systems of coagulation cascade (intrinsic TEM-INTEM, extrinsic TEM-EXTEM, FIBTEM) was used to measure the coagulation time (CT), clot formation time (CFT), alpha angle (alpha) and maximum clot firmness (MCF). No significant difference was found in the prothrombin time, partial thromboplastin time, thrombin time, fibrinogen and platelet count between the two groups. INTEM-CT and INTEM-CFT and EXTEM-MCF were significantly higher in the diabetic group compared with controls (P = 0.012, P = 0.007 and P = 0.029, respectively). INTEM alpha in the diabetic group was significantly lower than the controls (P = 0.001). All other parameters, including INTEM-MCF, EXTEM-CT, EXTEM-CFT, EXTEM-alpha, FIBTEM-CT, FIBTEM-CFT, FIBTEM-MCF and FIBTEM-alpha, were similar between the two groups. Taking into account these data, we conclude that there is subtle activation of the extrinsic pathway with a concomitant decrement in the intrinsic pathway of the coagulation cascade in type 2 diabetes. The exact underlying mechanisms leading to these changes, and their consequences with regard to diabetic complications, remain to be determined.
Assuntos
Coagulação Sanguínea , Diabetes Mellitus Tipo 2/diagnóstico , Tromboelastografia/métodos , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/tratamento farmacológico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valores de Referência , Fatores de TempoRESUMO
Hemostatic changes due to vascular endothelial damage are seen during the course of hematopoietic stem cell transplantation (HSCT). The fibrinolytic response to ongoing hemostatic activation in HSCT remains to be elucidated. Global fibrinolytic capacity (GFC) is a novel method, which reflects the amount of generated D-dimer when fibrinolysis of a freeze-dried fibrin clot is stopped by introducing aprotinin. GFC is sensitive to all the factors involved in the process of fibrinolysis. The aim of this study was to serially assess GFC at certain critical time points (days -1, +7, +14, +21 prior to and following stem cell infusion) during the course of HSCT. The study group comprised 16 patients with hematological malignancies (11 women, five men; median age 32+/-9 years) in whom HSCT had been performed. Thirty healthy adults (21 women, nine men; median age 31+/-7 years) served as controls. In this study, global fibrinolytic response, as reflected by GFC, was unchanged despite ongoing hemostatic activation, as indicated by D-dimer, moreover GFC remained stable, despite the development of thrombocytopenia associated with HSCT prior to platelet engraftment. Our results indicate that a global fibrinolytic response was impaired as a compensatory response to endothelial activation and to other hemostatic changes seen in HSCT. Further studies in larger HSCT populations are warranted to better understand the implications of these findings.
Assuntos
Produtos de Degradação da Fibrina e do Fibrinogênio/metabolismo , Fibrinólise/fisiologia , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Hemostasia/fisiologia , Adulto , Estudos de Casos e Controles , Feminino , Produtos de Degradação da Fibrina e do Fibrinogênio/química , Humanos , Masculino , Fatores de TempoRESUMO
AIM: To investigate the major steps of thrombogenesis and to identify the differences in these steps between idiopathic patient group and control group. METHODS: Fibrinogenesis was studied by measuring the activated factor VII, total and free levels of tissue factor pathway inhibitor (TFPI). The fibrinolysis step was investigated by determining the global fibrinolytic capacity. The endothelial function was assessed by measuring the levels of soluble adhesion molecules, namely soluble intercellular adhesion molecule 1 (sICAM-1), soluble vascular cell adhesion molecule 1 (sVCAM-1) and soluble E-selectin molecule. The exclusion criteria from "idiopathic" patient group were abdominal surgery, pregnancy, use of oral contraceptives, anti-phospholipid syndrome, Behçet's disease, cancer, myeloproliferative diseases. The congenital factors like mutations of factor-V Leiden and prothrombin, deficiencies of proteins C and S, antithrombin, hyperhomocysteinemia and hyperfibrinogenemia were ruled out. The total number of patients was reduced from 96 to 9 (7 with portal vein thrombosis, 2 Budd Chiari syndrome) by exclusion criteria. RESULTS: The levels of adhesion molecules sICAM-1, sVCAM-1, free TFPI levels and global fibrinolytic capacity were significantly different (P<0.05) in the patient group indicating an endothelial dysfunction and a lower fibrinolytic activity. CONCLUSION: These results show that this patient group should be tested by means of endothelial dysfunction and managed differently.
Assuntos
Síndrome de Budd-Chiari/etiologia , Síndrome de Budd-Chiari/fisiopatologia , Endotélio Vascular/fisiopatologia , Adulto , Idoso , Coagulação Sanguínea , Síndrome de Budd-Chiari/sangue , Síndrome de Budd-Chiari/terapia , Progressão da Doença , Selectina E/sangue , Selectina E/fisiologia , Endotélio Vascular/patologia , Fator VII/análise , Fator VII/fisiologia , Feminino , Fibrinólise , Fibrose/fisiopatologia , Humanos , Molécula 1 de Adesão Intercelular/sangue , Molécula 1 de Adesão Intercelular/fisiologia , Lipoproteínas/sangue , Lipoproteínas/fisiologia , Fígado/irrigação sanguínea , Fígado/patologia , Masculino , Pessoa de Meia-Idade , Molécula 1 de Adesão de Célula Vascular/sangue , Molécula 1 de Adesão de Célula Vascular/fisiologiaRESUMO
Obesity and its associated metabolic complications can impair the physiologic regulation of fibrinolysis, leading to a hyper coagulable state. We aimed to assess circulating thrombin activatable fibrinolysis inhibitor (TAFI) levels in obese female patients and to test the effects of orlistat-induced weight loss on basal TAFI concentrations. Obese female outpatients age 18 and older, with a body mass index (BMI, calculated as weight in kilograms divided by the square of height in meters) of at least 30, were included into the study. Thirteen nonobese (median BMI, 22.60 kg/m(2)) age-matched females were taken as controls. Plasma TAFI levels were measured before orlistat administration and after 6 months of orlistat treatment in the obese group and only one measurement was done in the control group. Twenty-seven obese patients were recruited into the study. The median TAFI level of the control group was 124.00; this value was significantly lower than the basal TAFI level of the obese group (p < 0.001). TAFI levels after orlistat therapy were statistically significantly lower than basal TAFI levels (p < 0.001) in the obese group. Hemostatic abnormalities including TAFI alterations represent a link between obesity and vascular thrombosis. Effective interventions should be considered in improving the obesity-associated prothrombotic risk profile.
Assuntos
Carboxipeptidase B2/efeitos dos fármacos , Lactonas/administração & dosagem , Obesidade/tratamento farmacológico , Adulto , Pesos e Medidas Corporais , Carboxipeptidase B2/sangue , Estudos de Casos e Controles , Feminino , Hemostasia , Humanos , Lactonas/farmacologia , Pessoa de Meia-Idade , Orlistate , TromboseRESUMO
BACKGROUND: The regions of ruptured atherosclerotic plaques have numerous macrophages. Osteopontin that modulates macrophage function has been shown in atherosclerotic plaques. We aimed to study the plasma levels of osteopontin in patients with unstable angina or non-ST-seg ment elevation myocardial infarction (NSTEMI) and the rela tionship between osteopontin and the extent of the coronary artery disease (CAD). METHODS: We studied 65 patients with unstable angina or NSTEMI, 25 patients with stable angina and 18 patients as the control group. The extent of coronary artery stenosis was determined by the number of vessels with >50% stenosis. Plasma osteopontin concentrations were measured from the blood samples that were drawn immediately after admission to the emergency department in unstable angina/NSTEMI patients and before the coronary angiograph in the stable angina and control groups. RESULTS: The plasma osteopontin concentration was (495 118 ng/ml) significantly higher in the patients with unstable angina/NSTEMI compared to the stable angina group (319 106 ng/ml) and control group (125+/-54 ng/ml) (p=0.0001 The plasma osteopontin levels were lower in the patients with stable angina pectoris who had one-vessel disease compared to those with two-vessel disease (p=0.01). How ever, in the unstable angina/NSTEMI group, the plasma osteopontin levels were statistically not different among the patients with one-vessel, and two-vessel and three-vessel disease (p=NS). There was no correlation between the plasma osteopontin levels and the extent of coronary stenosis. CONCLUSIONS: The plasma osteopontin levels are elevatedin patients with unstable angina/NSTEMI, but there appears to be no correlation with the extent of CAD. These results ma suggest that osteopontin may have a role in the pathobiology of ACS.
Assuntos
Angina Instável/sangue , Estenose Coronária/sangue , Isquemia Miocárdica/sangue , Osteopontina/sangue , Idoso , Angina Pectoris/sangue , Biomarcadores/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , SíndromeRESUMO
OBJECTIVE: Global fibrinolytic capacity (GFC) is a sensitive method reflecting all of the molecular components involved in the process of fibrinolysis. Recently, a decrease in GFC has been shown in women with polycystic ovary syndrome (PCOS). Girls with premature adrenarche (PA) have been shown to have hyperinsulinemia and dyslipidemia in addition to hyperandrogenemia, similar to women with PCOS. The aim of this study was to evaluate GFC levels in girls with PA. PATIENTS AND METHODS: Twenty-five girls with PA, who had developed pubic/axillary hair at age of 7.09 +/- 0.74 (5.1-7.9) years, were studied at the age of 10.04 +/- 1.53 years and compared with 20 age-matched healthy controls and 10 girls with PCOS (mean age 16.58 +/- 1.46 years). RESULTS: Median DHEAS and free testosterone levels were significantly higher in girls with PA than in the control group. The median serum sex hormone binding globulin (SHBG) level was higher in controls than in both PA and PCOS groups (49.85, 38.60 and 21.30 nmol/l, respectively). The median fasting glucose:insulin ratio (FGIR) levels were similarly low in PA and PCOS groups, while it was significantly higher in controls. The FGIR levels were less than 7 in 52% of girls with PA and 50% of girls with PCOS; however, in controls, only 5% of girls had FGIR <7. Median GFC in girls with PA (1.67 microg/ml) and PCOS (1.06 microg/ml) were significantly lower than that of the controls (3.48 microg/ml, p <0.001). The GFC level correlated positively with SHBG and FGIR. CONCLUSION: A reduction in GFC was demonstrated in girls with PA compared to healthy controls. This important finding, newly added to previous ones, may strengthen the view that PA is not a benign condition, and also points to the presence of potential risk factors for vascular diseases in these girls starting from childhood.