Increased circulating endothelial cells and microparticles in patients with psoriasis.

INTRODUCTION: Psoriasis is a chronic pathology characterized by increased inflammation that can be associated with changes in the vascular endothelium. We quantified the levels of circulating endothelial cells (CECs) and microparticles (MPs) in patients with psoriasis in order to analyze their relationship with endothelial and inflammation markers, subclinical atherosclerosis and microcirculation. METHODS: We studied 20 patients and 20 controls. Circulating markers of endothelial damage (CEC, MPs and von Willebrand factor, vWF) and inflammation (E-selectin, E-sel; Interleukin-6, IL-6 and C-reactive protein, CRP) were determined. Subclinical atherosclerosis was assessed by carotid ultrasound to obtain intima-media thickness. Microcirculation was evaluated by nailfold capillaroscopy. RESULTS: CECs, MPs, vWF, CRP and E-sel levels were significantly elevated in patients when compared with controls (p <  0.05). Ninety-four and fifty-three percentage of patients had CEC and MP levels higher than 99th percentile in controls. Forty-seven percent of patients simultaneously showed increased CEC and MP levels. MPs correlate with the inflammatory markers and with the intima-media thickness. CECs correlate with the capillaries loops per mm (p <  0.05). CONCLUSION: Psoriasis patients show elevated CECs and MPs, as a sign of endothelial dysfunction, which correlates with inflammatory markers as well as subclinical atherosclerosis and some capillaroscopy findings.

Circulating endothelial cells and procoagulant microparticles in patients with glioblastoma: prognostic value.

AIM: Circulating endothelial cells and microparticles are prognostic factors in cancer. However, their prognostic and predictive value in patients with glioblastoma is unclear. The objective of this study was to investigate the potential prognostic value of circulating endothelial cells and microparticles in patients with newly diagnosed glioblastoma treated with standard radiotherapy and concomitant temozolomide. In addition, we have analyzed the methylation status of the MGMT promoter. METHODS: Peripheral blood samples were obtained before and at the end of the concomitant treatment. Blood samples from healthy volunteers were also obtained as controls. Endothelial cells were measured by an immunomagnetic technique and immunofluorescence microscopy. Microparticles were quantified by flow cytometry. Microparticle-mediated procoagulant activity was measured by endogen thrombin generation and by phospholipid-dependent clotting time. Methylation status of MGMT promoter was determined by multiplex ligation-dependent probe amplification. RESULTS: Pretreatment levels of circulating endothelial cells and microparticles were higher in patients than in controls (p<0.001). After treatment, levels of microparticles and thrombin generation decreased, and phospholipid-dependent clotting time increased significantly. A high pretreatment endothelial cell count, corresponding to the 99(th) percentile in controls, was associated with poor overall survival. MGMT promoter methylation was present in 27% of tumor samples and was associated to a higher overall survival (66 weeks vs 30 weeks, p<0.004). CONCLUSION: Levels of circulating endothelial cells may have prognostic value in patients with glioblastoma.

Circulating endothelial cells and microparticles as prognostic markers in advanced non-small cell lung cancer.

BACKGROUND: Circulating endothelial cells and microparticles have prognostic value in cancer, and might be predictors of response to chemotherapy and antiangiogenic treatments. We have investigated the prognostic value of circulating endothelial cells and microparticles in patients treated for advanced non-small cell lung cancer. METHODOLOGY/PRINCIPAL FINDINGS: Peripheral blood samples were obtained from 60 patients before first line, platinum-based chemotherapy +/- bevacizumab, and after the third cycle of treatment. Blood samples from 60 healthy volunteers were also obtained as controls. Circulating endothelial cells were measured by an immunomagnetic technique and immunofluorescence microscopy. Phosphatidylserine-positive microparticles were evaluated by flow cytometry. Microparticle-mediated procoagulant activity was measured by the endogen thrombin generation assay. RESULTS: pre- and posttreatment levels of markers were higher in patients than in controls (p<0.0001). Elevated levels of microparticles were associated with longer survival. Elevated pretreatment levels of circulating endothelial cells were associated with shorter survival. CONCLUSIONS/SIGNIFICANCE: Circulating levels of microparticles and circulating endothelial cells correlate with prognosis, and could be useful as prognostic markers in patients with advanced non-small cell lung cancer.

Circulating endothelial cells in patients with heart failure and left ventricular dysfunction.

INTRODUCTION AND AIMS: Acute and chronic heart failure may manifest different degrees of endothelial damage and angiogenesis. Circulating endothelial cells (CEC) have been identified as marker of vascular damage. The aim of our study was to evaluate the evolution of the CEC at different stages of patients with heart failure. We also investigated a potential correlation between CEC and markers of vascular damage and angiogenesis. METHODS: We studied 32 heart failure patients at hospital admission (acute phase) and at revision after 3 months (stable phase) and 32 controls. Circulating markers of endothelial damage (CEC; von Willebrand factor, vWF and soluble E-selectin, sEsel) and angiogenesis (vascular endothelial growth factor, VEGF and thrombospondin-1) were quantified. RESULTS: Levels of CEC, vWF, sEsel and VEGF are significantly higher in heart failure patients than in controls. Levels of CEC (36.9 ± 15.3 vs. 21.5 ± 10.0 cells/ml; p< 0.001), vWF (325 ± 101 vs. 231 ± 82%; p< 0.001) and VEGF (26.3 ± 15.2 vs. 21.9 ± 11.9 ng/ml; p< 0.001) are significantly higher in the acute phase than in the stable phase of heart failure. CEC levels correlate with vWF and VEGF. RESULTS show than 100% of patients in acute phase and 37.5% in stable phase have levels of CEC higher than the 99th percentile of the distribution of controls (16 cells/ml). Therefore, increases in CEC represent a relative risk of 9.5 for heart failure patients suffering from acute phase. CONCLUSIONS: CEC, in addition to being elevated in heart failure, correlate with vWF levels, providing further support for CEC as markers of endothelial damage. Levels of CEC are associated with the acute phase of heart failure and could be used as a marker of the worsening in heart failure.

Células endoteliales y micropartículas circulantes en pacientes portadores de anticuerpos antifosfolípidos / Circulating endothelial cells and microparticles in patients with antiphospholipid antibodies

Fundamento y objetivo: Determinar si los valores de células endoteliales circulantes (CEC), micropartículas circulantes (MP) y factor von Willebrand (FvW), marcadores establecidos de disfunción/daño endotelial, están elevados en pacientes portadores de anticuerpos antifosfolípidos (AAF) y si existe correlación con marcadores de inflamación y coagulación. Pacientes y método: Se estudian 12 pacientes portadores de AAF y 12 sujetos sanos. Se determinaron CEC, MP, FvW, proteína C reactiva (PCR), fibrinógeno (Fg), ácido siálico (AS), interleucina 6, factor tisular (FT), generación de trombina (GT) y fragmentos de protrombina (F1+2) y de fibrina (DD). Resultados: En los pacientes están significativamente elevados los valores de los marcadores de: disfunción/daño endotelial (CEC, MP y FvW), inflamación (Fg y PCR) y coagulación (FT y DD). El análisis bivariante muestra correlación significativa entre CEC y Fg, AS, PCR y DD, así como entre CEC y FvW y MP. Conclusión: Los pacientes portadores de AAF presentan una disfunción endotelial asociada a un proceso inflamatorio, que, unido a los valores elevados de Fg, FT y DD, puede inducir un estado de hipercoagulabilidad (AU)

Background and objective: To determine whether circulating endothelial cells (CECs), circulatingmicroparticles (MPs) and von Willebrand factor (vWF), established markers of endothelial dysfunction/ damage, are elevated in patients with antiphospholipid antibodies (aPL) and its possible correlation with inflammation and coagulation. Patients and methods: Twelve atients with aPL and 12 healthy subjects were studied. Levels of CECs, MPs, vWF, C reactive protein (CRP), fibrinogen (Fg), sialic acid (SA), interleukin 6 (IL-6), tissue factor (TF), thrombin generation (TG) and prothrombin (F1 + 2) and fibrin (DD) fragments were determined. Results: In patients, markers of dysfunction/damage endothelial, CECs, MPs and vWF; inflammation, Fgand CRP and coagulation, TF and DD were significantly elevated. The bivariate analysis showedsignificant correlation among CECs and Fg, AS, CRP and DD, as well as between CECs and vWF and MPs.Conclusion: Patients with aPL had endothelial dysfunction associated with an inflammatory process,which, together with high levels of Fg, TF and DD, may be responsible for the hypercoagulable state (AU)

[Circulating endothelial cells and microparticles in patients with antiphospholipid antibodies]. / Células endoteliales y micropartículas circulantes en pacientes portadores de anticuerpos antifosfolípidos.

BACKGROUND AND OBJECTIVE: To determine whether circulating endothelial cells (CECs), circulating microparticles (MPs) and von Willebrand factor (vWF), established markers of endothelial dysfunction/damage, are elevated in patients with antiphospholipid antibodies (aPL) and its possible correlation with inflammation and coagulation. PATIENTS AND METHODS: Twelve patients with aPL and 12 healthy subjects were studied. Levels of CECs, MPs, vWF, C reactive protein (CRP), fibrinogen (Fg), sialic acid (SA), interleukin 6 (IL-6), tissue factor (TF), thrombin generation (TG) and prothrombin (F1+2) and fibrin (DD) fragments were determined. RESULTS: In patients, markers of dysfunction/damage endothelial, CECs, MPs and vWF; inflammation, Fg and CRP and coagulation, TF and DD were significantly elevated. The bivariate analysis showed significant correlation among CECs and Fg, AS, CRP and DD, as well as between CECs and vWF and MPs. CONCLUSION: Patients with aPL had endothelial dysfunction associated with an inflammatory process, which, together with high levels of Fg, TF and DD, may be responsible for the hypercoagulable state.

Atorvastatin neutralises the thrombin-induced tissue factor expresion in endothelial cells via geranylgeranyl pyrophosphate.

Statins may have beneficial effects in atherogenesis given their antithrombotic properties involving non-lipid mechanisms that modify endothelial function of tissue factor induction by thrombin. In this study, we investigate the effect of atorvastatin on tissue factor (TF) activity in thrombin-stimulated endothelial cells and its regulation through mevalonate or its derivatives. First subculture of human umbilical endothelial cells was used for this study. Cells were treated with thrombin and atorvastatin for different time intervals and dosage. Tissue factor activity was measured as Factor Xa generation induced by Tissue Factor-Factor VIIa complex on confluent cells. Our results show that atorvastatin prevents the thrombin-induced up-regulation of tissue factor activity in a concentration-dependent manner. Mevalonate and geranylgeranyl pyrophosphate reversed this inhibitory effect of atorvastatin on tissue factor activity, while the presence of farnesyl pyrophosphate did not prevent the atorvastatin effect on thrombin-induced tissue factor activity. Rho-kinase inhibitor did not affect the thrombin stimulation of tissue factor activity. High amount of hydrophobic isoprenoid groups decreases the thrombin-induced TF activity and may promote endothelial cell anti-thrombotic action. Rho kinase pathways do not have a major role in the thrombin-mediated TF activity. The inhibitory effect of atorvastatin on thrombin-induced TF activity was partially reversed by MVA and GGPP but not FPP.

Circulating markers of angiogenesis, inflammation, and coagulation in patients with glioblastoma.

Inflammation, angiogenesis, and coagulation are linked to the development of cancer. In glioblastoma, microvascular proliferation is a hallmark, and lymphocytic infiltration is a common finding. Thromboses are frequent in patients with glioblastoma. The objective of this study was to assess presurgical levels of circulating markers of inflammation, angiogenesis, and coagulation in a prospective series of patients with glioblastoma, and to explore their correlations and possible associations with clinical findings. Angiogenesis markers included were vascular endothelial growth factor (VEGF), soluble vascular endothelial growth factor-receptor 1 (sVEGFR-1), and thrombospondin-1 (TSP-1). Inflammatory markers included were C-reactive protein (CRP), interleukin-6 (IL-6), tumor necrosis factor alpha (TNFα), and sialic acid (SA). Coagulation markers included were fibrinogen (Fg), endogen thrombin generation (ETG), prothrombin fragments 1 + 2 (F1 + 2), and tissue factor (TF). Forty-seven patients and 60 healthy subjects were included in the study. Signs of tumor necrosis in presurgical MRI were associated with shorter survival (P < 0.01). All inflammation markers, F1 + 2, ETG, VEGF and sVEGFR-1, were significantly elevated in glioblastoma patients. Correlations were found between ETG and Fg (r = 0.44, P < 0.01). Sialic acid correlated with Fg (r = 0.63, P < 0,001); CPR correlated with SA (r = 0.60, P < 0.001), Fg (r = 0.76, P < 0.001), TNFα (r = 0.56, P < 0.001), and IL-6 (r = 0.65, P < 0.001); and IL-6 also correlated positively with TNFα (r = 0.40, P < 0.02) and Fg (r = 0.45, P < 0.01). Vascular endothelial growth factor inversely correlated with sVEGFR-1 (r = -0.35, P < 0.02). No associations were found between marker levels and survival or progression-free survival.

Inflammatory markers in stable heart failure and their relationship with functional class.

INTRODUCTION AND OBJECTIVES: While it appears to be clear that an inflammatory process occurs in heart failure (HF), it is still to be defined whether inflammation depends to a greater extent on HF etiology, functional class (FC), or the extent of depression of ejection fraction (EF). Our objectives were to analyze differences in inflammatory marker levels as compared to a healthy population, to assess differences depending on HF etiology, and to relate values with FC and EF. PATIENTS AND METHODS: Fifty-nine consecutive outpatients with stable HF (57 + or - 9 years, 89% males) and 59 controls (55 + or - 8 years, 85% males) were enrolled into the study. Causes of HF included ischemic heart disease (n=24), idiopathic dilated cardiomyopathy (n=24), and miscellaneous conditions (n=11). Patients with decompensation in the past 6 months were excluded from the study. Protein fibrinogen, sialic acid, C-reactive protein (CRP), and tumor necrosis factor-alpha (TNF-alpha) were measured. Echocardiography was performed in all study patients. FC was assessed using the NYHA classification. RESULTS: A comparison of inflammatory marker levels between the HF and control groups showed significant differences in all markers, except for TNF-alpha. Protein fibrinogen in controls: 253 + or - 54 mg/dl, protein fibrinogen in HF: 294 + or - 67 mg/dl; p<0.05. Sialic acid in controls: 53 + or - 1 mg/dl, sialic acid in HF: 61 + or - 12 mg/dl; p<0.05. CRP in controls: 1.3 + or - 0.7 mg/dl, CRP in HF: 7.8 + or - 1.2 mg/dl; p<0.05. TNF-alpha in controls: 183 + or - 51 ng/ml, TNF-alpha in HF: 203 + or - 13 ng/ml; p=0.2. No differences were found between the different etiologies of HF. A positive association was seen between FC and protein fibrinogen and TNF-alpha (p<0.05), but not with EF. CONCLUSIONS: Increased inflammatory marker levels related to FC of the patient, but not to EF, are found in chronic HF.

Effect of oral anticoagulant therapy on thrombospondin-1 and von Willebrand factor in patients with stable heart failure.

INTRODUCTION: Heart failure (HF) is associated with coagulation activation, abnormal inflammation and endothelial dysfunction. High levels of von Willebrand factor (VWF) may manifest endothelial dysfunction and hypercoagulable state. The haemostatic activity of VWF is a function of multimers size; only large multimers of VWF are haemostatically active. Thrombospondin-1 (TSP-1) reduces the average multimer size of VWF. Patients with HF are in risk of thromboembolic events and oral anticoagulation therapy (OAT) has been shown to prevent it. This study was designed to evaluate whether VWF and TSP-1 levels are modified by OAT in stable HF patients. The effect of OAT on markers of inflammation and coagulation was also investigated. MATERIALS AND METHODS: Fifty-nine patients with stable HF were studied and 33 of them received OAT. VWF, TSP-1, fibrinogen, prothrombin fragment 1+2 (F1+2), tissue factor (TF), D-dimer, endogenous thrombin generation (ETG), C reactive protein (CRP), tumour necrosis factor alpha (TNFalpha) and interleukin 6 (IL-6) were measured. RESULTS: Stable HF patients receiving OAT had higher VWF (p=0.02) and lower TSP-1 (p=0.02), ETG and F1+2 (p=0.003) than patients without OAT. However, there were no significant differences in the levels of fibrinogen, TF, D-dimer, CRP, IL6 and TNFalpha. The TSP-1/VWF ratio in patients receiving AOT was significantly lower than in patients without OAT (p=0.005). CONCLUSION: OAT may have a dual effect on the haemostatic profile in stable HF by reducing thrombin generation and increasing the VWF. The decrease of TSP-1 induced by OAT may be clinically effective in neoangiogenesis. The increase of VWF in patients receiving anticoagulant treatment may also reflect an effect of OAT on endothelial dysfunction.

Inflammation, endothelial dysfunction and angiogenesis markers in chronic heart failure patients.

This study was conducted to assess the relationship among circulating markers of inflammation, endothelial dysfunction and angiogenesis in 59 chronic heart failure (CHF) patients. Increased concentrations of C-reactive protein (CRP), tumour necrosis factor-alpha (TNF-alpha), von Willebrand factor (VWF) and fibrinogen are strongly implicated in the development of CHF. Increased vascular endothelium grow factor (VEGF) and decreased thrombospondin-1 (TSP-1) concentrations suggest a role of angiogenesis in the maintenance and repair of luminal endothelium in CHF. A relationship among markers of endothelial dysfunction (VWF) and inflammation (fibrinogen, CRP) and angiogenesis (VEGF, TSP-1) was found in CHF patients.

Atorvastatin neutralizes the up-regulation of thrombospondin-1 induced by thrombin in human umbilical vein endothelial cells.

Statins have been reported to affect blood vessel formation. Thrombospondin-1 (TSP-1) is a multifunctional protein that affects vasculature systems such as platelet activation, angiogenesis, and wound healing. This study was designed to investigate the effect of atorvastatin on TSP-1 synthesis in thrombin-stimulated human umbilical vein endothelial cells (HUVECs), and its regulation by mevalonate or its derivatives. The results showed that atorvastatin down-regulated TSP-1 expression in HUVECs. This effect was fully reversed by mevalonate, farnesylpyrophosphate (FPP), and gerarylgeranylpyrophosphate (GGPP). Furthermore, farnesyltransferase and geranylgeranyltransferase inhibitors decreased TSP-1expression. It was also found that thrombin increased TSP-1 expression in HUVECs. Atorvastatin (0.1, 1, and 10 muM) decreased TSP-1 in thrombin-stimulated cells (45%, 66%, and 80%). Mevalonate partially reversed this inhibitory effect of atorvastatin on TSP-1, whereas the presence of FPP and GGPP did not alter TSP-1. Rho-kinase inhibitor neutralized the up-regulation of TSP-1 induced by thrombin. In conclusion, atorvastatin inhibits TSP-1 expression in endothelial cells via the mevalonate pathway. Rho protein activation is necessary for up-regulation of TSP-1 synthesis induced by thrombin. Because FPP and GGPP are essential for the activity of Rho proteins, inhibition of these proteins may constitute the mechanism by which atorvastatin inhibits thrombin up-regulated TSP-1 expression.

Sialic acid is an inflammation marker associated with a history of deep vein thrombosis.

INTRODUCTION: Deep vein thrombosis (DVT) induces a systemic chronic inflammation and it has been associated with atherosclerosis. Increased levels of total sialic acid (TSA) have been shown to correlate with inflammation and atherosclerotic processes. The aim of this study was to investigate whether or not increased levels of TSA are associated with a history of DVT and with inflammation and coagulation markers, as well as with the lipid profile. MATERIALS AND METHODS: TSA, fibrinogen, C-reactive protein (CRP), fibrin D-dimer (D-dimer), prothrombin fragment 1+2 (F1+2), endogenous thrombin generation, cholesterol and triglycerides were measured in 68 patients who had suffered, in the previous 6-12 months, a first episode of idiopathic DVT, and in 68 age- and sex-matched healthy subjects. RESULTS: Levels of TSA, fibrinogen, CRP and D-dimer observed in patients were significantly higher than those detected in healthy subjects. TSA positively correlated with fibrinogen (R=0.47, p<0.01), cholesterol (R=0.46, p<0.01), triglycerides (R=0.38, p<0.01) and CRP (R=0.28, p<0.05). The logistic regression analysis confirmed that both high fibrinogen (> or =340 mg/dl) and cholesterol (> or =267 mg/dl) levels significantly and independently influence the TSA concentration. TSA levels above the 95th percentile of controls (>72 mg/dl) were detected in 33% of patients (OR=8.9; p<0.0001; 95% CI 2.4 to 31.7). CONCLUSIONS: Patients with a history of DVT had associated high levels of TSA. In these patients, TSA correlated to markers of inflammation activity and lipid profile. Thus, TSA appears to be a useful vascular inflammatory marker in idiopathic DVT.

Influence of plasma and erythrocyte factors on red blood cell aggregation in survivors of acute myocardial infarction.

Increased erythrocyte aggregation (EA) has been observed in patients with ischaemic heart disease (IHD), although most of these studies have been performed in the acute phase when reactant proteins may account for this increase. Little is known about the role played by the erythrocyte itself in this aggregation process. To ascertain the contribution of both plasma and erythrocyte factors to EA in IHD, we investigated the following parameters in 78 survivors of acute myocardial infarction (AMI) and in a well-matched control group of 98 subjects: EA, glucose, total cholesterol (T-Chol), low-density lipoprotein-cholesterol (LDL-Chol), high-density lipoprotein-cholesterol (HDL-Chol), triglycerides, apolipoproteins A(1) and B, protein and functional fibrinogen, plasma sialic acid, membrane sialic acid, and the cholesterol and phospholipid content of the erythrocyte membrane. AMI survivors showed higher glucose (p<0.001), a borderline increase in triglycerides (p = 0.043), and a statistical decrease in Apo A(1) (p= 0.003) relative to controls. EA, functional fibrinogen, and plasma sialic acid were statistically higher in AMI survivors than in controls (p= 0.001; p<0.001; p= 0.011, respectively). Membrane sialic acid content was statistically lower in AMI patients than in controls (p= 0.026). No differences were observed in either membrane cholesterol or phospholipids. Multivariate logistic regression analysis, in which EA was dichotomized as higher or lower than 8.7, demonstrated that triglyceride levels higher than 175 mg/dL (OR= 7.7, p= 0.001) and functional fibrinogen levels higher than 320 mg/dL (OR= 3.7, p= 0.004) were independently associated with a greater risk of erythrocyte hyperaggregability. Our results suggest that plasma lipids, predominantly triglycerides, and fibrinogen may not only enhance the development of ischaemic events by their recognized atherogenic mechanisms, but also by increasing EA.

Effect of unfractionated heparin and a low molecular weight heparin (enoxaparin) on coagulant activity of cultured human endothelial cells.

BACKGROUND AND OBJECTIVES: Unfractionated heparin and low molecular weight heparins exert their anticoagulant effect by mobilizing tissue factor pathway inhibitor (TFPI) from the vascular endothelium into the blood circulation. We compared the influence of unfractionated heparin and enoxaparin on the anticoagulant function of cultured human endothelial cells. DESIGN AND METHODS: Monolayers of human umbilical vein endothelial cells were treated with 10 U/mL unfractionated heparin or enoxaparin for different periods of time (30min-48h). Endothelial cell procoagulant activity was determined in the cell lysates by a chromogenic assay. Endothelial cell tissue factor (TF) and released TFPI and von Willebrand factor (vWF) was determined. RESULTS: In short periods of incubation (30min-2h), both heparins reduced endothelial cell procoagulant activity, the inhibition produced by unfractionated heparin being greater than that induced by enoxaparin (p<0.05). However, no variations were observed in TFPI and vWF release. With long periods of incubation (24-48h), both unfractionated heparin and enoxaparin significantly increased TFPI release (control vs. unfractionated heparin, p<0.05-0.001; control vs. enoxaparin, p<0.01-0.001) and also reduced the release of vWF in the culture medium, though no variations in endothelial cell procoagulant activity or TF content were observed. INTERPRETATION AND CONCLUSIONS: Our findings show that unfractionated heparin and enoxaparin exert different kinds of effects on endothelial cells. With short incubation periods, procoagulant endothelial cell capacity was reduced to a greater extent by unfractionated heparin, while after longer periods of incubation enoxapain increased the anticoagulant activity of the endothelial cells to a greater degree than did unfractionated heparin.

Association between inflammation and hemostatic markers in atherothrombotic stroke.

INTRODUCTION: It has been reported that the influence of fibrinogen on the incidence of ischemic events is related to inflammation processes and reflects an association with advance atherosclerosis. The aim of this study was to evaluate the association of thrombogenic and inflammatory profiles in patients who have suffered a stroke. MATERIALS AND METHODS: The study involved 17 patients with atherothrombotic stroke and 34 healthy subjects as control group. The patients were examined 48 h, 3 and 6 months after the stroke occurred. To determine the inflammatory and thrombogenic profiles, plasma levels of fibrinogen, total sialic acid (TSA), C-reactive protein (CRP), tissue factor (TF) and fibrin D-dimer (D-dimer) were measured. RESULTS: The study showed that at 48 h and 3 months the levels of fibrinogen, TF, D-dimer, TSA and CRP were significantly higher than control group. TF, D-dimer and TSA remains significantly elevated throughout the entire study period. TF and D-dimer decreased over time without reaching the normal values. The multiple regression analysis showed that, at 48 h, 68% of the variance of fibrinogen and 22% of the variance of TF could be explained by the influence of CRP. At 3 and 6 months, 78% of the variance of fibrinogen could be explained by the influence of TSA. CONCLUSIONS: The results suggest a relation among inflammation markers, fibrinogen and TF in the acute phase of stroke. As TF and D-dimer are still elevated at 6 months, an increased thrombogenicity for a longer period following the acute event is present.

Inflammation, fibrinogen and thrombin generation in patients with previous myocardial infarction.

BACKGROUND AND OBJECTIVES: It has been reported that the influence of plasma fibrinogen on the incidence of myocardial infarction is related to inflammatory processes. The aim of this study was to investigate the relationship between inflammatory activity, fibrinogen and thrombin generation in patients 5 years after the acute phase of myocardial infarction. DESIGN AND METHODS: Sixty-seven patients 5 years after a myocardial infarction and 67 control subjects were studied. Plasma fibrinogen protein (Fg-protein) and function (Fg-function), prothrombin fragment 1+2 (F1+2), thrombin-antithrombin complex (TAT), total sialic acid (TSA) and C-reactive protein (CRP) were measured. RESULTS: The levels of Fg-protein, Fg-function, F1+2, TAT, TSA and CRP were significantly higher in patients than in the control subjects. Plasma TSA correlated with CRP (r=0.31, p<0.05). There was a significant correlation between TSA and Fg-protein or Fg-function (r=0.48, p<0.01). CRP correlated with Fg-function (r=0.32, p<0.05) while there was no correlation between CRP and Fg-protein. CRP also correlated with F1+2 and TAT (r= 0.4, p<0.01). INTERPRETATION AND CONCLUSIONS: Five years after myocardial infarction there was clear evidence of low-grade inflammation that was accompanied by an increase in thrombin formation. The increase of the plasma fibrinogen level is mainly related to TSA and the increase of CRP, which is associated with thrombin generation.