The effect of streptokinase neutralizing antibodies on fibrinolytic activity and reperfusion following streptokinase treatment in acute myocardial infarction

Abstract. Nilsson JB, Nilsson TK, Jansson J‐H, Boman K, Söderberg S, Näslund U (Heart Centre, University Hospital, Umeå; Örebro Medical Centre, Örebro; Skellefteå Hospital, Skellefteå; Sweden). The effect of streptokinase neutralizing antibodies on fibrinolytic activity and reperfusion following streptokinase treatment in acute myocardial infarction. J Intern Med 2002; 252: 405–411. Objectives. To evaluate tissue plasminogen activator (tPA) activity as a measure of fibrinolytic response to treatment with streptokinase (SK) and to relate this to the effect of pretreatment SK antibodies and to successful reperfusion assessed by continuous computerized vectorcardiography (VCG). Setting. Umeå University Hospital. Subjects. A total of 104 patients with acute myocardial infarction (AMI) treated with SK and no history of previous SK treatment were studied. The tPA activity was measured 4 h after the start of treatment. The effect of pre‐existing neutralizing antibodies to SK was analysed with a functional assay in pretreatment samples. Reperfusion was evaluated with VCG. Main outcome measures. Successful reperfusion. Results. Fifty‐five patients (53%) were classified as successfully reperfused. The risk for failed reperfusion was calculated in logistic regression models. In a univariate model, a borderline significant increase in the risk of failed reperfusion was observed in intermediate levels of SK neutralizing antibodies, but not in the highest levels. In a multivariate model, only high tPA activity, >25 U mL^?1, at 4 h (OR 0.17; 95% CI: 0.06–0.51) was associated with a higher rate of reperfusion whilst longer time to treatment (OR 1.17; 95% CI: 1.02–1.35) was associated with a higher risk of failed reperfusion. There was no significant correlation between neutralizing antibodies to SK and tPA activity at 4 h. Conclusion. The SK treatment of AMI induced high levels of tPA activity which were associated with successful reperfusion. The effect of pre‐existing SK antibodies had no significant influence on reperfusion and were not correlated to the fibrinolytic activity obtained.     

Fibrinolysis in patients with a mild-to-moderate bleeding tendency of unknown cause

In more than 50% of patients with a mild-to-moderate bleeding tendency, no underlying cause can be identified (bleeding of unknown cause, BUC). Data on parameters of fibrinolysis in BUC are scarce in the literature and reveal discrepant results. It was the aim of this study to investigate increased fibrinolysis as a possible mechanism of BUC. We included 270 patients (227 females, median age 44 years, 25–75^th percentile 32–58) with BUC and 98 healthy controls (65 females, median age 47 years, 25–75^thpercentile 39–55). Tissue plasminogen activator (tPA-) antigen and activity, plasminogen activator inhibitor type-1 (PAI-1), tPA-PAI-1 complexes, thrombin activatable fibrinolysis inhibitor (TAFI), α2-antiplasmin, and D-dimer were determined. While PAI-1 deficiency was equally frequent in patients with BUC and controls (91/270, 34%, and 33/98, 34%, p = 0.996), tPA activity levels were more often above the detection limit in patients than in controls (103/213, 48%, and 23/98, 23%, p < 0.0001). We found lower levels of tPA-PAI-1 complexes (6.86 (3.99–10.00) and 9.11 (7.17–13.12), p < 0.001) and higher activity of TAFI (18.61 (15.80–22.58) and 17.03 (14.02–20.02), p < 0.001) and α2-antiplasmin (102 (94–109) and 98 (90–106], p = 0.003) in patients compared to controls. Detectable tPA activity (OR 3.02, 95%CI 1.75–5.23, p < 0.0001), higher levels of TAFI (OR 2.57, 95%CI 1.48–4.46, p = 0.0008) and α2-antiplasmin (OR 1.03, 95%CI 1.01–1.05, p = 0.011), and lower levels of tPA-PAI-1 complexes (OR 0.90, 95%CI 0.86–0.95, p < 0.0001) were independently associated with BUC in sex-adjusted logistic regression analyses. We conclude that the fibrinolytic system can play an etiological role for bleeding in patients with BUC.     

氯沙坦和阿替洛尔对高血压患者纤溶系统及血浆血管性血友病因子的作用比较

目的比较血管紧张素受体拮抗剂(ARB)氯沙坦和β受体阻滞剂阿替洛尔对原发性高血压患者纤溶系统及血浆血管性血友病因子(vWF)的影响。方法轻中度原发性高血压患者60例随机分成氯沙坦组和阿替洛尔组(每组30例),分别给予氯沙坦50mg/(次.d)或阿替洛尔50mg/(次.d),共治疗8周。每4周随访1次,4周时血压如不达标(BP<140/90mmHg)则加用双氢克尿噻12.5mg/(次.d)。治疗前后行血浆组织型纤溶酶原激活物(tPA)及纤溶酶原激活物抑制剂1(PAI-1)检测,并计算PAI-1/tPA作为纤溶参数,同时测定血浆vWF的含量。结果两组的基线血压等一般情况具有可比性。治疗4周及8周时两组血压均较治疗前显著下降,组间比较无差异。同治疗前相比,氯沙坦组治疗8周时血浆PAI-1和vWF水平下降(P值分别<0.05及<0.01),PAI-1/tPA也有显著下降(P<0.05),而tPA则无显著变化(P>0.05);阿替洛尔组治疗8周时血浆PAI-1和vWF水平及PAI-1/tPA均无显著变化,而tPA则有所上升(P<0.05)。治疗后血浆vWF两组间比较,差异有非常显著意义。结论氯沙坦治疗能改善原发性高血压患者的纤溶系统并降低血浆vWF,而阿替洛尔则未见有此作用。     

Short term effects of GnRH agonists on plasma fibrinolytic balance in patients with advanced prostate cancer

Background Gonadotropin releasing hormone (GnRH) agonists are the cornerstone of metastatic prostate cancer treatment. Cardiovascular effects of GnRH agonists are unclear. In this study, we investigated the short term effects of GnRH agonists on plasma fibrinolytic parameters in patients with metastatic prostate cancer. Methods Eleven patients (mean age 69.3 ± 6.5) with metastatic prostate cancer and a clinical indication for GnRH agonist therapy were selected. Plasma plasminogen activator inhibitor (PAI-1) antigen (Ag), tissue plasminogen activator (t-PA) Ag and thrombin-activatable fibrinolysis inhibitor (TAFI) activity levels were measured at baseline and at 4 weeks after the first dose of GnRH agonist, Goserelin Acetate (Zoladex^®, subcutaneous administration, 10.8 mg). Results Serum prostate specific antigen (PSA) levels significantly decreased from 36.6 ± 19.3 to 1.1 ± 0.3 ng/ml after Goserelin acetate treatment (P = 0.005). Significant changes occurred in the fibrinolytic parameters. GnRH agonists decreased plasma t-PA Ag levels (16.3 ± 4.9 vs. 12.2 ± 2.8 ng/ml, P = 0.047) and increased PAI-1/t-PA molar ratio (4.8 ± 3.6 vs. 6.6 ± 3.4, P = 0.16), on the other hand, plasma PAI-1 Ag (59.0 ± 48.5 vs. 56.4 ± 30.5 ng/ml, P = 0.8), and TAFI levels (130.6 ± 9.5 vs. 124.2 ± 26.5% activity, P = 0.3) did not change significantly. Conclusion This study provides evidence that GnRH agonists may inhibit fibrinolytic system by decreasing t-PA levels.     

Southern copperhead venom enhances tissue-type plasminogen activator induced fibrinolysis but does not directly lyse human plasma thrombi

In addition to degrading fibrinogen as a source of consumptive coagulopathy, purified fractions of southern copperhead (Agkistrodon contortrix contortrix; A. c. contortrix) venom has been demonstrated to enhance fibrinolysis. The goal of this investigation was to characterize the kinetic fibrinolytic profile of A. c. contortrix venom in the absence and presence of tissue-type plasminogen activator (tPA) to determine if intact venom had tPA independent fibrinolytic properties. Utilizing thrombelastographic methods, the coagulation and fibrinolytic kinetic profiles of human plasma exposed to A. c. contortrix venom (0–6 μg/ml) were determined in the absence or presence of tPA (0–100 IU/ml). Then, plasma was exposed to 0–6 μg/ml of venom without tPA added and coagulation observed for 3 h. Venom significantly prolonged the onset of coagulation, decreased the velocity of thrombus growth but did not significantly decrease clot strength. In the presence of tPA, venom significantly decreased clot strength, shortened the time of onset of fibrinolysis, decreased clot lysis time but did not significantly affect the maximum rate of lysis. Lastly, while venom exposure in the absence of tPA significantly prolonged the onset of coagulation and decreased the velocity of clot growth, venom exposure did not result in detectable fibrinolysis over the 3 h observation period. A. c. contortrix venom enhances tPA mediated fibrinolysis by degrading plasma coagulation kinetics. Intact A. c. contortrix venom does not possess sufficient fibrinolytic activity to cause fibrinolysis in human plasma at the concentration tested.     

Hypo-fibrinolysis in patients with hypertension and elevated cholesterol

To test the hypothesis that increased blood pressure and hyperlipidaemia result in changes in the fibrinolytic system, 84 subjects with both hypertension and elevated serum cholesterol levels (the high risk group) were compared with 55 controls matched with respect to age, sex and body mass index (BMI). Plasminogen activator inhibitor (PAI-1), and tissue plasminogen activator (tPA) antigen and activity were measured before and after venous occlusion. In the high risk group, tPA activity was significantly lower both before and after venous occlusion and PAI-1 levels were significantly higher. In a multivariate analysis the triglyceride levels, diastolic blood pressure and cholesterol levels were independently associated with the PAI-1 levels. Diastolic blood pressure was independently and inversely associated with resting tPA activity. We conclude that patients with hypertension and hyperlipidaemia have a reduced activity of the fibrinolytic system, an effect which is unrelated to differences in age, sex, smoking or BMI.     

Impact of antioxidants and HDL on glycated LDL-induced generation of fibrinolytic regulators from vascular endothelial cells

Hyperglycemia and dyslipoproteinemia are biochemical markers of diabetes mellitus (DM). Elevated levels of plasminogen activator inhibitor-1 (PAI-1) with and without reduction of tissue plasminogen activator (tPA) in plasma have been frequently found in patients with DM. Our previous studies indicated that glycation enhances low density lipoprotein (LDL)-induced production of PAI-1 and further decreases tPA generation in vascular endothelial cells (ECs). The present study demonstrated that treatment with antioxidants, butylated hydroxytoluene or vitamin E, blocked native LDL- and glycated LDL-induced changes in PAI-1 and tPA generation in ECs. Native or glycated high density lipoprotein (HDL) did not significantly alter tPA generation in ECs. Glycated but not native HDL (>/=100 microg/mL) moderately increased PAI-1 release from ECs. Cotreatment with native or glycated HDL inhibited LDL-induced or glycated LDL-induced changes in PAI-1 and tPA generation in ECs. The abundance of conjugated dienes was increased in glycated or EC-modified LDL. Treatment with butylated hydroxytoluene, vitamin E, or HDL reduced the abundance of conjugated dienes in glycated or EC-modified LDL. The effects of antioxidants and HDL on LDL-induced or its glycated LDL-induced changes in the generation of PAI-1 and tPA were also found in cultured human coronary artery ECs. The findings of the present study suggest that antioxidants and HDL may attenuate native LDL- or glycated LDL-induced changes in the generation of fibrinolytic regulators from vascular ECs, which possibly results from their inhibition on the lipid peroxidation of LDL particles. Treatment with antioxidants or hypolipidemic agents potentially improves fibrinolytic activity and reduces thrombotic tendencies in patients with DM.     

ACE/DD genotype is associated with hemostasis balance disturbances reflecting hypercoagulability and endothelial dysfunction in patients with untreated hypertension

BACKGROUND: Angiotensin-converting enzyme (ACE) gene polymorphism has been associated with an increased incidence of myocardial infarction. Recent studies have investigated a potential influence of ACE gene polymorphism on fibrinolysis or endothelial function. It has been previously established that essential hypertension is accompanied by endothelial dysfunction and fibrinolytic balance disorders. The aim of our study was to study the relation between ACE gene polymorphism and fibrinolytic/hemostatic factors as well as endothelial cell damage markers in patients with hypertension. METHODS: The following parameters were evaluated in 104 patients with previously untreated hypertension: plasminogen activator inhibitor-1 (PAI-1), tissue plasminogen activator (tPA) antigen, fibrinogen, D-dimer, and von Willebrand factor (vWF). The genotype of the ACE gene was also determined (by the polymerase chain reaction method), and patients were characterized according to the observed alleles as deletion/deletion (DD), insertion/insertion (II), or insertion/deletion (ID). RESULTS: Those with DD genotype (n = 42) had significantly higher plasma levels of PAI-1 antigen (P =. 012), tPA antigen (P =.0001), fibrinogen (P =.0002), D-dimer (P =. 0001) and vWF (P =.0004) compared with ID (n = 30) or II (n = 32) genotypes. The ACE gene genotypes appeared to be significant predictors for plasma PAI-1 antigen, tPA antigen, fibrinogen, D -dimer, and vWF even after adjustment for age, sex, body mass index, triglyceride and cholesterol levels, and blood pressure. CONCLUSIONS: Our findings suggest that the ACE/DD genotype is associated with hemostasis balance disturbances reflecting hypercoagulability and endothelial damage in patients with untreated hypertension.     

Plasma levels of complement activation fragments C3b and sC5b-9 significantly increased in patients with thrombotic microangiopathy after allogeneic stem cell transplantation

Transplantation-associated thrombotic microangiopathy (TA-TMA) is an uncommon but severe complication in patients undergoing allogeneic stem cell transplantation (allo-SCT). However, the mechanism is unclear. From 2011 to 2014, 20 patients with TA-TMA, 20 patients without, and 54 patients with various other complications, including veno occlusive disease (VOD), graft-versus-host disease (GVHD), and infection, were recruited in the study. Plasma vWF antigen (vWFAg), vWF activity (vWFAc), and ADAMTS13 activity were determined in these patients by ELISAs and FRETS-vWF73 assay, respectively. Plasma C3b, sC5b-9, and CH50 were also determined by ELISAs. Plasma levels of C3b were significantly increased in patients with either TA-TMA (p < 0.0001) or GVHD (p < 0.01). Plasma sC5b-9 and CH50 levels in patients with TA-TMA were also significantly increased (p < 0.001). Plasma ADAMTS13 activity was lower in patients with VOD, but normal with other complications. Both plasma vWFAg and vWFAc levels were not elevated in patients with TA-TMA or VOD compared with those of other groups. Complement activation likely via an alternative pathway (increased C3b, sC5b-9, and CH50) may play a role in the pathogenesis of TA-TMA. ADAMTS13 activity is reduced in VOD, but the ADAMTS13/vWF axis appears to be unaffected in patients with TA-TMA.     

Plasma levels of tissue plasminogen activator/plasminogen activator inhibitor-1 complex and von Willebrand factor are significant risk markers for recurrent myocardial infarction in the Stockholm Heart Epidemiology Program (SHEEP) study

An impaired fibrinolytic function due to elevated plasma levels of plasminogen activator inhibitor (PAI)-1 activity or tissue plasminogen activator (tPA) antigen is correlated with the development of myocardial infarction (MI) in patients with manifest coronary heart disease. Recently, methods for determining the specific tPA/inhibitor complexes constituting tPA antigen in plasma have become available. In the Stockholm Heart Epidemiology Program (SHEEP) study, 86 of 1212 MI patients, subjected to blood sampling in a metabolically stable period, suffered reinfarction before the end of 1996. These individuals have been compared with an approximately equal number of matched MI patients without recurrence and a group of matched healthy control subjects regarding the plasma concentrations of some hemostatic factors. The hemostatic compounds studied (fibrinogen, von Willebrand factor, tPA antigen, PAI-1, and the tPA/PAI-1 complex) were typically higher in the groups (men and women) with recurrence of MI compared with those without. The plasma concentrations were also typically higher in the pooled groups of patients compared with the groups of healthy control subjects. The largest between-group differences were found for the plasma tPA/PAI-1 complex. The crude odds ratio for reinfarction associated with higher concentration (>/=75th percentile among the control subjects) of tPA/PAI-1 was 1.8 (95% CI 1.1 to 3.1); the corresponding crude odds ratio for von Willebrand factor was 2.3 (1. 3 to 4.0). The tPA/PAI-1 complex correlated strongly with PAI-1 and tPA antigen in all groups and with serum triglycerides and body mass index in all groups except for women with reinfarction. An increased plasma level of tPA/PAI-1 complex is a novel risk marker for recurrent MI in men and women. Most likely, increased plasma levels of tPA/PAI-1 complex reflect impaired fibrinolysis, because the correlation with PAI-1 is strong. Further support is obtained indicating that the plasma concentration of von Willebrand factor is also an important risk marker for recurrent MI.     

Sex-related differences in the associations between hyperleptinemia, insulin resistance and dysfibrinolysis

The adipocyte-derived hormone leptin is associated with insulin resistance and reduced fibrinolytic status--or dysfibrinolysis--in humans. As leptin associates differentially to the development of cardiovascular disease and diabetes in men and women, we hypothesized that leptin and insulin sensitivity are related to dysfibrinolysis in a sex-dependent manner. Thirty-two men and 40 women were recruited from the Monitoring of trends and determinants in Cardiovascular disease (MONICA) population sample, representing the highest and lowest quartiles of fasting insulin levels. Lipids, fibrinolytic status [plasminogen activator inhibitor 1 (PAI-1) activity, tissue plasminogen activator (tPA) mass and activity, and tPA-PAI complex], leptin, testosterone and sex-hormone-binding globulin were measured. Insulin sensitivity was estimated using the euglycaemic clamp technique. Body composition was determined by bioimpedance. Determinants for circulating levels of fibrinolytic factors were explored in a multivariate linear regression analysis. Levels of fibrinolytic variables and estimated insulin sensitivity did not differ between men and women. Leptin was independently associated with reduced fibrinolytic status (high PAI-1 activity, low tPA activity, high tPA mass, and high tPA-PAI complex) in men (P < 0.001-0.002). In women, fat mass and/or insulin sensitivity were related to these factors (P < 0.001-0.03), and leptin only to reduced tPA activity (P = 0.002). Hyperleptinemia, dysfibrinolysis, insulin sensitivity and androgenicity associate differentially in men and women.     

疏血通注射液对心房颤动患者血栓前状态的影响

目的研究疏血通注射液对心房颤动患者血栓前状态的改善作用。方法将63例心房颤动患者随机分为疏血通组和对照组,疏血通组应用疏血通注射液治疗14d,对照组除不使用疏血通,其他用药与疏血通组相同。治疗前和治疗2周后测量两组血浆纤溶酶原激活物(tPA)及其抑制物(PAI-1)活性,D-二聚体(D-D)和血管性假血友病因子(vWF)水平。结果疏血通组和对照组在治疗前血浆tPA、PAI-1活性、D-D和vWF水平无统计学意义(P>0.05)。疏血通组治疗后血浆tPA活性显著性增高(P<0.05),血浆PAI-1活性、D-D和vWF水平均显著性下降(P<0.05),而对照组无显著性改变(P>0.05)。组间比较发现,疏血通组治疗后血浆PAI-1活性、D-D和vWF水平比对照组更低(P<0.05),而血浆tPA活性无显著增高(P>0.05)。结论短期疏血通静脉输注可以明显改善心房颤动患者的血栓前状态,这可能降低心房颤动患者的血栓栓塞危险。     

Glycaemic Control,Smoking Habits and Diabetes Duration Affect the Extrinsic Fibrinolytic System in Type I Diabetic Patients but Microangiopathy Does Not

ABSTRACT The fibrinolytic system was studied in 43 type I diabetic patients with long duration of the disease, with or without evidence of microangiopathy, and in 26 control subjects. There were positive and independent correlations between tissue plasminogen activator (tPA) activity after venous occlusion and HbA_lc, and between triglycerides and plasminogen activator inhibitor (PAI-1) and tPA antigen concentrations before and after venous occlusion. The tPA activities both at rest and after venous occlusion were higher in the patients. There were no differences with regard to sex, hypertension or nephropathy for the levels of fibrinolytic variables in these patients. Subjects with retinopathy did not differ from those without retinopathy. Diabetes duration showed a significant negative association with tPA activity in multivariate regression analysis. Tobacco-smoking diabetics, as compared to non-smoking, had an increased tPA antigen release at venous occlusion, but also higher PAI-1 levels and reduced specific activity of the tPA protein. When assessed with the new specific assays now available, the fibrinolytic parameters appear to be specific indicators of endothelial dysfunction related to smoking and to degree of glycaemic control in type I diabetic subjects.     

Influence of autoimmunity and inflammation on endothelial function and thrombosis in systemic lupus erythematosus patients

The aim of this study is to assess the relationship between autoimmunity and endothelial activation/damage (ICAM-1 and vWF serum levels) and the degree of prothrombotic activity (thrombin–antithrombin complexes—TAT serum levels) in SLE. In 60 clinically stable SLE patients, levels of the following parameters were estimated in their serum: lupus anticoagulant (LA), anticardiolipin antibodies in both IgG and IgM classes (aCL-IgG and aCL-IgM, respectively), antiβ2GPI antibodies in both IgG and IgM classes (antiβ2GPI-IgG and antiβ2GPI-IgM, respectively), ICAM, von Willebrand factor (vWF), TAT, CRP, C3c, C4, and IL-6. ICAM-1 values exceeded the upper reference limit in 9 (15%) patients. vWF levels were increased in 21 (35%) patients. In all patients with elevated ICAM-1 values, vWF were also increased. TAT concentrations were elevated in 12 (20%) people. ICAM-1 were significantly higher in patients with elevated aCL-IgM (>?30 MPL vs ≤?30 MPL; p <?0.05). Similarly, ICAM-1 were significantly higher in patients with elevated antiβ2-GPI-IgM (>?20 SMU vs ≤?20 SMU; p <?0.05). There was no significant difference in ICAM-1 levels in relation to LA-positivity. vWF were not significantly different in relation to antiphospholipid antibodies nor the inflammation marker levels. TAT were significantly higher in patients with elevated aCL-IgM (>?30 MPL vs ≤?30 MPL; p <?0.05). In one third of young patients with stable SLE, signs of endothelial activation/damage were found, as shown by elevated plasma ICAM-1 or vWF. Increased prothrombotic tendency manifested by elevated TAT was found in one fifth of the patients. Elevated anticardiolipin (IgM) and anti-β2-glycoprotein I (IgM) antibodies influence endothelial dysfunction and enhance prothrombotic state.     

Markedly impaired fibrinolytic balance contributes to cardiovascular risk in adults with growth hormone deficiency

CONTEXT: Adults with GH deficiency (GHD) have multiple cardiovascular risk factors, including an unfavorable lipid profile and body composition as well as impairments in endothelial function and cardiac performance. We hypothesized that GHD is associated with elevated levels of plasminogen activator inhibitor-1 (PAI-1), the major inhibitor of plasminogen activation in the circulation. OBJECTIVE: The objective of the study was to determine the fibrinolytic profile of adults with GHD in comparison with controls. STUDY DESIGN AND PARTICIPANTS: This was a prospective, observational study including 12 adults with GHD. Twelve gender-, age-, and body mass index-matched adults served as controls. MAIN OUTCOME MEASURES: The primary outcome measures were circadian plasma PAI-1 antigen with corresponding tissue-plasminogen activator (tPA) activity values. Endothelial function was assessed by flow-mediated vasodilation and fibrinolytic potential by venous occlusion test. RESULTS: Adults with GHD exhibited an unfavorable 24-h fibrinolytic profile characterized by a mean 62% elevation in PAI-1 antigen (2.77 ng/ml after adjustment for baseline PAI-1; P = 0.049) in the setting of a mean 24% reduction in tPA activity (-0.17 IU/ml after adjustment for baseline tPA; P = 0.003). Fibrinolytic response was defective in GHD, as demonstrated by a sustained elevation in PAI-1 activity greater than 4 IU/ml after venous occlusion [7.2 IU/ml (interquartile range 0.8-17.4); P = 0.018]. Endothelial function was impaired in GHD, as quantified by percent flow-mediated vasodilation over 120 sec [area under the curve 3.8 (interquartile range -2.4 to 7.9) vs. 12.8 (interquartile range 2.1-19.4); P = 0.043]. CONCLUSIONS: Adults with GHD demonstrate alterations in plasma fibrinolytic balance, including elevated levels of PAI-1 antigen with decreased tPA activity. These changes may contribute to the increased cardiovascular morbidity within this population.     

Microalbuminuria,von Willebrand factor and fibrinogen levels as markers of the severity in COPD exacerbation

In COPD, the systemic effects of the disease reflect the structural and/or biochemical alterations occurring in the structures or organs other than the lungs in relation to the characteristics of the primary disease. The disorders of endothelial structures due to COPD may lead vascular pathologies, such as ischemic heart disease, stroke, to occur more commonly in those with COPD. On consideration of the fact that the vascular endothelium is a major site in which the systemic effect of the inflammation occurs, should von Willebrand Factor, a clotting factor of endothelium origin, and the plasma level of fibrinogen vary with the severity of the disease in COPD, the variability of arterial blood gas values, and the stability or exacerbation of the disease? Considering the fact that microalbuminuria is an indirect manifestation of the renal endothelial permeability and/or renal perfusion; should there be an association between microalbuminuria and the severity of COPD? Therefore, in order to assess the effect of the systemic inflammation in COPD on the vascular endothelium, we compared the levels of the plasma vWF, fibrinogen, 24-h urine microalbuminuria of those with stable COPD (33 patients) and exacerbation of COPD (26 patients) with those of the controls (16 healthy subjects). The mean age was 63.42 ? 10.29, 68.00 ? 9.77 and 59.63 ? 14.10 years in SCOPD, COPDAE, and CG, respectively. The level of microalbuminuria was found to increase significantly in COPDAE group, compared to that of the controls (P = 0.004). When we investigated the relation between smoking burden and microalbuminuria, vWF, fibrinogen levels, the amount of consumption and positive relationship were found significant. (r = 0.336, P = 0.003 between smoking pack-years and vWF, r = 0.403, P = 0.001 between smoking pack-years and fibrinogen, and r = 0.262, P = 0.02 between smoking pack-years and microalbuminuria). The levels of vWF and fibrinogen are AECOPD > SCOPD > CG, with the highest being in AECOPD, and the difference among the groups was statistically significant. The relationship between the level of hypoxemia and microalbuminuria, fibrinogen and vWF was found to be significant (r = ?0.360, P = 0.005 between oxygen saturation and microalbuminuria, r = ?0.359, P = 0.005 between the level of PaO₂ and fibrinogen, and r = ?0.336, P = 0.009 between PaO₂ and vWF). In conclusion, the levels of plasma vWF, fibrinogen, and microalbuminuria may be helpful in grading the severity of COPD exacerbation. The related increase in these markers may represent a possible pathophysiological mechanism behind the increased vascular morbidity of patients with COPD and detecting indirectly the endothelial dysfunction as a manifestation of systemic outcomes due to COPD and in detecting earlier the cases in which the risk for developing the associated complications are higher. We suggest that further studies are necessary to investigate the impact of antithrombotic treatment on microalbuminuria, plasma vWF and fibrinogen as markers of endothelial dysfunction coexisting COPD exacerbation.     

氯沙坦和依那普利对心肌梗死后纤溶-凝血功能的影响

目的　探讨氯沙坦和依那普利对急性心肌梗死 (AMI)患者纤溶 凝血功能的影响。方法　将 41例AMI患者随机分为氯沙坦组、依那普利组和对照组 ,以发色底物法和ELISA法测定三组患者入院即刻、发病 2周、2个月的血浆PAI 1活性、纤溶酶原激活物 (tPA)抗原水平和血管血友病病因子(vWF)含量。结果　与对照组相比 ,氯沙坦组 2周和 2个月时的PAI 1活性分别减低 2 2 % (P <0 0 1)和 18% (P <0 0 5 ) ,tPA抗原水平分别减低 32 % (P <0 0 1)和 2 5 % (P <0 0 5 ) ;依那普利组相应分别减低 2 8% (P <0 0 1)和 2 1% (P <0 0 5 ) ,tPA抗原水平分别减低 38% (P <0 0 1)和 2 9% (P <0 0 5 ) ;两个治疗组之间差异无显著性。两种药物对vWF含量均无影响。结论　氯沙坦和依那普利可改善心肌梗死后的纤溶功能 ,长期应用这两种药物可能会降低心肌梗死后发生急性心脏事件的危险。     

Age-related effects of regular physical activity on hemostatic factors in men

Background Age-related changes in blood coagulation and fibrinolytic factors are associated with an increase in risk of thrombotic events. The purpose of this study was to assess the effects of age, regular aerobic exercise and detraining on blood coagulation and fibrinolytic factors in men. Methods Initially, 41 sedentary and 42 physically active men (20–64 years) were analyzed for plasma levels of coagulation and fibrinolytic factors. Twelve sedentary men were then subjected to 16-week aerobic exercise training and subsequent 2-week detraining. Their blood samples taken at rest were assayed for activity levels of prothrombin, coagulation factor (F) V, VII, VIII, IX, X, XI and XIII, antithrombin III, protein C and plasminogen, and for antigen levels of fibrinogen, prothrombin fragment 1 + 2 (F1 + 2), FIX, protein C, tissue-type plasminogen activator (tPA), plasminogen activator inhibitor 1 (PAI-1) and tPA/PAI-1 complex. Results Plasma levels of most coagulation factors, particularly for fibrinogen and FIX antigens as well as FXIII activity significantly increased with aging in sedentary men, while that tendency disappeared in physically active men. By the exercise training, plasma antigen and/or activity levels of most blood coagulation factors except for prothrombin and FIX decreased. These training-effects, however, disappeared after detraining, and in some cases even rebounded to higher levels than those of pre-training. Plasma antigen levels of tPA, PAI-1 and tPA/PAI-1 complex decreased with the training and remained low even after detraining. Conclusion Regular aerobic exercises give complex effects on expression of hemostatic factors, overall favoring the hemostatic balance to less thrombotic, partly cancelling out the age effects.     

Reduced plasminogen activator inhibitor activity in high consumers of fruits, vegetables and root vegetables

We studied a cross-sectional sample of 260 subjects aged 30-60 years, in order to assess the relation between food intake habits and factors of the fibrinolytic system. Plasma samples of tissue plasminogen activator (tPA) antigen, and plasminogen activator inhibitor (PAI-1) activity were obtained for the assay. The dietary pattern was determined using a food frequency questionnaire, according to which the subjects were grouped as high, low or medium consumers. The subjects who were high consumers of fruit, vegetables, and root vegetables showed the lowest levels of PAI-1, those who were low consumers had the highest levels, whereas the medium consumers showed intermediate values. The tPA levels did not differ between the three groups, and there were no significant differences in other variables that covaried with PAI-1 levels, such as age, anthropometric variables, or serum lipid levels, which could confound the PAI-1/food pattern relationship. The data, which show that a frequent intake of fruit, vegetables, and root vegetables--foodstuffs rich in vitamin C and fibre--is associated with lower PAI-1 levels, are consistent with increased activity of the fibrinolytic system and thus a reduced risk of thromboembolic and cardiovascular disease in subjects who exhibit this food intake pattern.     

持续气道正压通气对OSAHS患者血管内皮细胞及纤溶系统的影响

为探讨经鼻持续气道正压通气（nCPAP)治疗前后阻塞性睡眠呼吸暂停低通气综合征（OSAHS）患者血管内皮细胞及纤溶系统的变化及临床意义，选择年龄，性别，体重指数（BMI）无明显差异的OSAHS患者38例和健康者对照组32例，用多导睡眠呼吸监测仪进行监测，以凝固法测定纤维蛋白原（Fg），发色底物法测组织纤溶酶原激活物活性（tPA：A）、纤溶酶原激活物抑制物－1活性（PAI－1：A），酶联免疫法测vonWillebrand因子（vWF)、组织纤溶酶原激活物抗原（tPA:Ag）、纤溶酶原含量（PLg:Ag)和纤溶酶原激活物抑制物－1含量（PAI－1：Ag）。结果OSAHS组与对照组比较，vWF,Fg,tPA:Ag、PAI－1：A明显升高（P分别＜0．01，0．001，0．001，0．01），PLg:Ag、tPA:A、tPA:Ag、最低血氧饱和度（SaO2low)明显降低（P分别＜0．01，0．001，0．001，0．01).nCPAP治疗后与治疗前比较，vWF,Fg,PAI-1:Ag,PAI-1:A明显降低（P分别＜0．05，0．01，0．01，0．01），PLg:Ag,tPA:A,tPA:Ag，最低SaO2明显升高（P分别＜0．05，0．001，0．001，0．01）。提示OSAHS患者血管内皮细胞损伤，凝血功能增强，纤溶系统功能减弱;nCPAP治疗能部分纠正各指标的异常。