Impaired fibrinolytic capacity in rheumatic mitral stenosis with or without atrial fibrillation and nonrheumatic atrial fibrillation

Chronic atrial fibrillation (AF) has often been associated with systemic embolization, and patients with mitral stenosis (MS) have the highest thromboembolic risk. Increased risk of thromboembolism could be in part due to impaired fibrinolytic function. Global fibrinolytic capacity (GFC) is an innovative technique for evaluating the entire fibrinolytic system.The aim of our study was to evaluate fibrinolytic activity in patients with rheumatic and nonrheumatic chronic AE To investigate fibrinolytic activity, we assessed GFC in peripheral blood samples of 32 patients with nonrheumatic AF (14 women; mean age, 56 +/- 1 years), 30 patients with rheumatic MS and AF (23 women; mean age, 35 +/- 9 years), and 32 patients with rheumatic MS and sinus rhythm (24 women; mean age, 36 +/- 8 years). The control group comprised 30 healthy adult subjects in normal sinus rhythm. Patients with chronic AF (rheumatic and nonrheumatic) had lower GFC than did the controls (P = .0001). The rheumatic AF group also showed decreased levels of GFC compared with the nonrheumatic AF group, with the rheumatic MS and sinus rhythm group, and with controls (P = .03, P = .02, P = .0001, respectively). GFC was lower in patients with rheumatic MS and sinus rhythm than in controls (P = .003). Although there were correlations between GFC and mitral valve area, transmitral mean gradient, left atrial diameter, and mitral calcification in patients with rheumatic MS, multivariate analysis showed only transmitral gradient as an independent factor affecting GFC. Patients with AF have decreased GFC, a finding that suggests the presence of a hypofibrinolytic state. Fibrinolytic dysfunction was more pronounced in rheumatic MS patients with AF than in those with nonrheumatic AF. Moreover, patients with rheumatic MS and sinus rhythm had decreased global fibrinolytic activity. Hypofibrinolysis documented by decreased GFC can be one of the important causes of increased risk of embolism in patients with AF and rheumatic MS.     

Fibrinolytic activity in multiple myeloma

The incidence of thromboembolic events is high as a result of disease, disease-related complications, and therapy in multiple myeloma (MM). In patients with hematologic tumors, impaired fibrinolysis may be present and may contribute to the development of thrombotic complications. Therefore, we designed a study to investigate fibrinolytic activity in MM. We compared plasma levels of interleukin (IL)-6, C-reactive protein (CRP), IL-1beta, IL-11, tissue plasminogen activator (tPA) activity, plasminogen activator inhibitor-1 (PAI-1) activity, and global fibrinolytic capacity (GFC) in patients with MM (n = 66) and in control subjects (n = 18). The prevalence of venous thromboembolism was 4.5%, with a median follow-up period of 7 months in our myeloma group. Results are given as mean (median, range). Plasma levels of IL-6 (8.27 +/- 0.74 [9.65, 0.90-13.32] pg/mL versus 2.64 +/- 0.66 [1.80, 0.10-11.86] pg/mL, P < 0.001), CRP (45.57 +/- 9.92 [21.00, 1.34-330.00] mg/L versus 1.96 +/- 0.50 [1.05, 0.19-8.03] mg/L, P < 0.001), PAI-1 (7.40 +/- 0.67 [5.57, 2.40-31.80] IU/mL versus 4.73 +/- 0.65 [3.60, 2.32-11.00] IU/mL, P < 0.01), GFC score (1.90 +/- 0.02 [2, 1-3] versus 2.50 +/- 0.14 [3, 1-3], P < 0.001) were increased compared with controls. In patients with MM, the level of IL-6 was positively correlated with CRP (r = 0.66, P < 0.001), IL-1beta (r = 0.29, P < 0.05), and PAI-1 (r = 0.35, P < 0.01) and negatively correlated with GFC (r = -0.37, P < 0.01). CRP level was positively correlated with plasma PAI-1 level (r = 0.40, P < 0.01) and negatively correlated with GFC (r = -0.44, P < 0.001). A significant negative correlation between PAI-1 level and GFC (r = -0.75, P < 0.001) was also detected. IL-1beta levels were negatively correlated with tPA level (r = -0.26, P < 0.05). These results suggest that patients with myeloma have a decreased fibrinolytic activity mainly because of increased PAI-1 activity. In MM, increased PAI-1 activity seems to be related with elevated IL-6 level. MM should be considered as a hypercoagulable state as a result of both increased procoagulant activity and decreased fibrinolytic activity. Achieving a plateau by means of conventional chemotherapies does not improve the decreased fibrinolytic activity.     

Effects of short-term atorvastatin treatment on global fibrinolytic capacity,and sL-selectin and sFas levels in hyperlipidemic patients with coronary artery disease

BACKGROUND: The beneficial effects of HMG-CoA reductase inhibitors (statins) in patients with coronary artery disease (CAD) appear to be attributable not only to their lipid-lowering properties, but also to their therapeutic effects on the coagulation system, and anti-inflammatory effect. Furthermore, statins mitigate the apoptosis of vascular smooth muscle cells (VSMC) and macrophages in atherosclerotic plaques. HYPOTHESIS: The purpose of this study was to evaluate the effects of short-term atorvastatin treatment on the fibrinolytic system and systemic inflammatory status, and on apoptosis in hyperlipidemic patients with CAD. METHODS: The study population consisted of 36 hyperlipidemic patients (14 women and 22 men, mean age 53+/-9 years) with stable CAD, untreated with lipid-lowering medications. Serum lipoproteins, fibrinogen levels, sFas and sL-selectin, and global fibrinolytic capacity (GFC) were measured at baseline and after 12 weeks of treatment with atorvastatin, 10 mg/day. RESULTS: Atorvastatin treatment decreased serum low-density lipoprotein (-39%, P=0.0001), total cholesterol (-32%, P=0.0001), and triglycerides (-22%, P=0.0001), and increased high-density lipoprotein (+13%, P=0.0001) at 12 weeks compared to baseline. These effects were associated with a decrease in plasma fibrinogen from 331+/-73 to 298+/-58 mg/dl (P=0.0001), and sL-selectin levels from 666+/-201 to 584+/-162 ng/ml (P=0.0001). sFas levels and GFC increased from 3754+/-1264 to 4873+/-1835 pg/ml and from 3.5+/-2.4 to 5.6+/-2.9 microg/ml, respectively (both P=0.0001). CONCLUSIONS: These results suggest that lipid lowering with atorvastatin therapy significantly increases GFC, decreases fibrinogen levels, and causes leukocyte deactivation. Our findings also suggest that atorvastatin treatment mitigates apoptosis of VSMC in the atherosclerotic plaque. These effects of atorvastatin may, in part, explain the early decrease in cardiovascular events observed in clinical trials of statins.     

Global fibrinolytic capacity is decreased in polycystic ovary syndrome,suggesting a prothrombotic state

The polycystic ovary syndrome (PCOS) is associated with an increased risk of cardiovascular disease (CVD). Insulin resistance (IR), hyperandrogenism, and dyslipidemia are well-known cardiovascular risk factors in PCOS. Impaired fibrinolysis could also contribute to the development of CVD in PCOS. Global fibrinolytic capacity (GFC) is a recently developed method, which is reflected by the amount of generated D-dimer when the 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. We evaluated whether women with PCOS have any alterations in the GFC and other essential hemostatic parameters. Fifty-nine nonobese, normal glucose-tolerant women with PCOS (age, 22.9 +/- 4.4 yr; body mass index, 23.0 +/- 2.4 kg/m(2) ) and 23 age- and body mass index-matched healthy controls participated. We measured GFC and triglycerides; total cholesterol; HDL-cholesterol (HDL-C); lipoprotein-a; prothrombin time; partial thromboplastin time; thrombin time; antithrombin III; factors II, V, VII, and X; fibrinogen; plasminogen; antiplasmin; and D-dimer. Serum glucose and insulin (at baseline and during a 75-g 2-h oral glucose tolerance test) were also measured, and IR was assessed by homeostatic model assessment. GFC was significantly lower in the PCOS group, compared with the control group (2.49 +/- 1.6 vs. 5.95 +/- 2.43 microg/ml, P < 0.001). All the other coagulation and fibrinolysis parameters were comparable between the two groups. The PCOS group had lower HDL-C and higher IR values. GFC was correlated with testosterone and free testosterone negatively and with HDL-C positively. There was no correlation between GFC and any of the IR parameters. Our results suggest that women with PCOS have impaired fibrinolysis, as reflected by the decreased GFC. This impairment is not related to the IR and may increase the risk of CVD in PCOS.     

Thrombin-activatable fibrinolysis inhibitor activity and global fibrinolytic capacity in Type 1 diabetes: evidence for normal fibrinolytic state

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.     

Effects of acute exercise on fibrinolysis and coagulation in patients with coronary artery disease

Acute physical exertion may trigger an acute coronary syndrome. Furthermore, acute physical exercise may influence hemostatic markers in healthy individuals. However, the effect of acute exercise on blood fibrinolysis and coagulation in patients with coronary artery disease (CAD) is still not well understood. Nineteen untrained patients with angiographically proven CAD (age, 58 +/- 9 years, 12 males), and 25 age- and sex-matched controls without CAD (age, 56 +/- 6 years, 16 males) underwent a treadmill exercise test. Global fibrinolytic capacity (GFC) and prothrombin fragment 1 + 2 (F 1 + 2) levels were measured before exercise, at peak exercise, and 2 hours after recovery. There were no differences between the groups with respect to left ventricular ejection fraction, history of hypertension, body mass index, and serum lipids. Before exercise, GFC was significantly lower in patients with CAD when compared with controls (1.40 +/- 0.43 versus 3.28 +/- 1.19 microg/mL, respectively; P < 0.001). In patients with CAD, F 1 + 2 levels were significantly higher than those of controls (1.15 +/- 0.43 versus 0.79 +/- 0.10 nmol/L, respectively; P = 0.002). In both study groups, GFC levels increased significantly at peak exercise and decreased to baseline values 2 hours after recovery. At peak exercise, F 1 + 2 levels significantly increased in both study groups. However, while F 1 + 2 levels of controls decreased to baseline values 2 hours after recovery (0.79 +/- 0.10 versus 0.80 +/- 0.10 nmol/L; P > 0.05), F 1 + 2 levels of patients with CAD were still significantly elevated (1.15 +/- 0.43 versus 1.84 +/- 0.06 nmol/L; P = 0.002). Acute exercise increases coagulation and fibrinolysis both in untrained subjects with and without CAD. However, in patients with CAD, the equilibrium between fibrinolysis and coagulation during peak exercise is disturbed in favor of coagulation after recovery.     

慢性阻塞性肺疾病患者炎症细胞因子与肺通气功能的相关研究

目的　探讨慢性阻塞性肺疾病 (COPD)患者肺通气功能改变与炎症因子变化之间的关系。方法　稳定期COPD和慢性支气管炎 (简称慢支 )患者各 8例 ,,另有 8名健康者作为对照 ,进行肺功能检查 ,并经支气管肺泡灌洗获取肺泡巨噬细胞进行培养 ,采用酶联免疫吸附 (ELISA)方法测定大肠杆菌内毒素 (LPS)刺激后上清液中白细胞介素 8(IL 8)、IL 1β、IL 6和肿瘤坏死因子α(TNF α)的浓度 ,细胞因子之间相关性采用Pearson相关阵分析 ,肺功能值与细胞因子相关性采用多元后退回归法分析。结果　 (1)肺泡巨噬细胞释放IL 8:加入LPS后COPD组为 [(43± 2 7) μg/L和 (5 7± 41) μg/L],与正常对照组 [(13± 10 ) μg/L和 (2 0± 13 ) μg/L) ]比较差异有显著性 (P <0 .0 5 ) ;与慢支组 [(2 9± 2 1)μg/L和 (3 2± 2 3 ) μg/L]比较差异有显著性 (P >0 .0 5 )。 (2 )加入LPS前、后 ,COPD组、慢支组和正常对照组肺泡巨噬细胞释放IL 1β分别为 [(5 0± 41)ng/L、(94± 5 9)ng/L、(3 7± 3 2 )ng/L、(2 2 5± 10 8)ng/L、(15 3± 175 )ng/L、(70± 3 7)ng/L],与IL 8的释放呈正相关 (P <0 .0 5 ) ;三组肺泡巨噬细胞在LPS刺激后释放TNF α分别为 [(12 3 8± 679)ng/L、(3 0 88± 2 879)ng/L、(13 3 2± 1846)ng/L],与IL 1β呈正相     

Oolong tea increases plasma adiponectin levels and low-density lipoprotein particle size in patients with coronary artery disease

BACKGROUND: Oolong tea has been studied for its effect on cardiovascular disease and obesity. Plasma adiponectin levels are reduced in obesity, in patients with type 2 diabetes mellitus and in coronary artery disease (CAD). OBJECTIVE: To investigate prospectively, whether intake of Oolong tea influences plasma adiponectin levels, low-density lipoprotein (LDL) particle size, total cholesterol, high-density lipoprotein (HDL) cholesterol, LDL cholesterol, serum triglyceride and plasma glucose levels in patients with CAD. METHODS: Twenty two patients in our study consumed Oolong tea (1000 ml) or water for 1 month in our randomized cross-over study design. RESULTS: There was a significant difference in plasma adiponectin levels before and after 1 month intake of Oolong tea (6.26 +/- 3.26 microg/ml versus 6.88 +/- 3.28 microg/ml, P < 0.05), and in plasma level LDL particle size (25.02+/-0.67 nm versus 25.31+/-0.60 nm, P < 0.01). The water-consuming control group showed no changes (6.28+/-3.28 microg/ml versus 6.23+/-3.21 microg/ml) in adiponectin levels or LDL particle sizes (25.03+/-0.70 nm versus 25.02+/-0.72 nm). We also observed a significant difference in hemoglobin A1c levels (7.23 +/- 4.45% versus 6.99 +/- 4.30%, P < 0.05) before and after intake of Oolong tea. CONCLUSION: Oolong tea may have beneficial effects on the progression of atherosclerosis in patients with CAD.     

Fibrinolysis and fibrinogenolysis in liver disease

Patients with liver disease frequently have hemostatic abnormalities which include accelerated fibrinolysis. In order to assess the fibrinolytic state in liver disease, plasma levels of fibrinogenolysis products (FgDP), fibrinolysis products (FbDP), and fibrinogenolysis plus fibrinolysis products (TDP) were measured with newly developed enzyme-linked immunosorbent assays based on monoclonal antibodies in 36 patients with liver disease (six patients with acute hepatitis, seven with chronic hepatitis, ten with liver cirrhosis, 11 with hepatocellular carcinoma, and two with intrahepatic cholestasis). As compared with healthy subjects, mean plasma levels of FbDP (1,083 +/- SD 1,254 vs. 236 +/- 100 ng/ml, P = 0.005) and TDP (1,773 +/- 1,814 vs. 669 +/- 212 ng/ml, P = 0.001) were significantly elevated in patients with liver disease, whereas FgDP was normal (389 +/- 202 vs. 396 +/- 132 ng/ml, P = 0.87). Plasma FbDP correlated very well with TDP (r = 0.986, P less than 0.00001) in liver disease. In addition, FbDP and TDP but not FgDP correlated with plasma concentrations of thrombin-antithrombin III complex. When plotted by the disease categories, the magnitude of elevations of FbDP and TDP was the most prominent in acute hepatitis followed by hepatocellular carcinoma. These findings indicate that activation of fibrinolysis occurs following thrombin generation, but increased primary fibrinogenolysis is rare in liver disease.     

Global fibrinolytic capacity increased exponentially in metastatic colorectal cancer.

Colorectal cancers are one of the most common malignancies associated with coagulation abnormalities ranging from asymptomatic laboratory changes to massive thromboembolism or hemorrhage. It was previously shown that global fibrinolytic was increased in non-metastatic colorectal cancer. In this study global fibrinolytic capacity was measured in patients with colorectal cancer and metastatic liver disease, which always more commonly displays various coagulation disorders. Nineteen patients with biopsy-proven colorectal cancer, 30 patients with metastatic colorectal cancer, and 20 healthy control subjects were involved into the study. Using standart silicated fibrin pellets and tissue plasminogen activator, fibrinolytic capacity of the plasmas was detected with the amount of d-dimer produced before the reaction was stopped by adding aprotinin to the medium. Mean global fibrinolytic capacity (GFC) was increased to higher levels in patients with metastatic disease compared to levels in non-metastatic disease (p<0.05). Fibrinogen/GFC ratio correlated to the increase of d-dimer levels. Global fibrinolytic capacity was much higher in metastatic disease, reflecting a progression to overt disseminated intravascular coagulation.     

Increased plasma fibrinolysis and tissue-type plasminogen activator/tissue-type plasminogen activator inhibitor ratios after ethanol withdrawal in chronic alcoholics.

The effects of alcohol withdrawal on fibrinolysis were studied in 10 middle-aged male chronic alcoholics institutionalized for withdrawal therapy. All patients were sampled on admission [day 1 (D1)] and 21 days after alcohol withdrawal [day 22 (D22)]. The overall plasma fibrinolytic capacity (OFC) was assayed by measuring the ability of patient plasma to generate D-dimers from a standardized fibrin clot, and tissue-type plasminogen activator (t-PA) and t-PA inhibitor (PAI-1) levels were assayed together with serum cholesterol, triglyceride and cholesterol fractions. At D22, the OFC significantly increased in seven patients [D1 = 10 +/- 0.7 microg/h (mean +/- SD), D22 = 17 +/- 7.4 microg/h; P < 0.01], while t-PA and PAI-1 levels decreased in all patients but two (t-PA: D1 = 16.6 +/- 5 ng/ml, D22 = 10.2 +/- 3.8 ng/ml; P < 0.001; and PAI-1: D1 = 46 +/- 39 ng/ml, D22 = 21 +/- 28 ng/ml; P < 0.01). This study clearly demonstrates an increase in overall fibrinolytic activity after alcohol withdrawal, which is mainly due to a decrease in PAI-1 levels. These changes induced by alcohol abstinence might provide clear benefit by reducing the risk of thromboembolic events and particularly of stroke associated with elevated PAI-1 levels described in heavy drinkers.     

Activation of coagulation system in dilated cardiomyopathy: comparison of patients with and without left ventricular thrombus

OBJECTIVES: We aimed to investigate plasma levels of molecular markers for platelet activity, thrombin activation and fibrinolytic status in patients with dilated cardiomyopathy (DCM) with and without left ventricular (LV) thrombus and to compare these markers between patients with DCM and control participants. MATERIALS AND METHODS: The study population comprised 60 patients with DCM who met the inclusion criteria. Patients were divided into two groups: 22 patients with LV thrombus and 38 patients without LV thrombus. The age-matched control group consisted of 23 healthy participants (18 men and five women with a mean age of 49). Patients with DCM and healthy participants were compared with respect to platelet activity, thrombin activation and fibrinolytic status. These comparisons were also performed in patients with DCM with and without LV thrombus. RESULTS: Platelet factor 4 (28.2+/-4.4 ng/ml compared with 20+/-3.1 ng/ml, P<0.01) and beta-thromboglobulin (40+/-2 ng/ml compared with 17+/-3 ng/ml) levels, reflecting platelet activity, were significantly higher in patients with DCM than in control participants. Fibrinopeptide A (6.94+/-0.69 ng/ml compared with 1.96+/-0.1 ng/ml, P<0.001) and thrombin-antithrombin III complex (5.26+/-2.60 ng/ml compared with 3.17+/-1.23 ng/ml, P<0.001) levels, as markers of fibrin generation, were also higher in patients with DCM than in normal participants. Plasma levels of D-dimer (118+/-16 ng/ml compared with 85+/-3 ng/ml, P<0.001) and plasmin-alpha2-plasmin inhibitor complex (0.8+/-1.1 microg/ml compared with 0.6+/-1.7 microg/ml, P<0.001) in patients with DCM significantly exceeded those in the normal participants. There were no statistically significant differences between patients with and without LV thrombus in DCM with respect to platelet activity, thrombin activation and fibrinolytic status. CONCLUSION: We have shown that platelet activation, thrombin activation and fibrinolytic activity are increased in patients with DCM compared to control participants. However, these markers reflecting coagulation activation in patients with LV thrombus are comparable to those in patients without LV thrombus.     

Contribution of mononuclear bone marrow cells to carbon tetrachloride-induced liver fibrosis in rats

AIM： To study the inhibitory effect of mononuclear bone marrow cell （BNC） transplantation on carbon tetrachloride （CCl4） -induced liver fibrosis in rats.
METHODS： Rat liver fibrosis models were induced by CCl4 and alcohol administration. After 8 wk, twenty rats were randomly allocated into treatment group （n = 10） and control group （n = 10）. BMC were infused into the rats in treatment group via the portal vein, while heparinized saline was infused in control group. CCl4 was hypodermically injected into the rats twice a week for 4 wk. At the end of wk 12, all rats were humanely sacrificed. Uver samples were taken and stained with HE or Masson trichrome. The general conditions, liver fibrosis （hydroxyproline and collagen fibre） and liver pathological grades in rats were evaluated.
RESULTS： The general conditions of the rats in treatment group improved markedly, but not in control group. Hydroxyproline was 504.6± 128.8 μg/g in treatment group, and 596.0 ± 341.8 μg/g in control group. The percentage of collagen fibre was 3.75% ± 0.98% in treatment group and 5.02% ± 0.44% in control group. There was a significant difference between the two groups （P 〈 0.05）. Liver pathological grade decreased from grade N to grade 11 partially in treatment group （P 〈 0.05） with no obvious improvement in control group （P 〉 0.05）. There was a significant difference between treatment group and control group （P 〈 0.05）.
CONCLUSION： Transplantation of BMC can improve liver fibrosis due to chronic liver injury in rats.     

肺血栓栓塞症患者凝血纤溶系统及肺血管内皮功能的变化

目的探讨肺血栓栓塞症(PTE)患者体内凝血纤溶系统及肺血管内皮功能的变化及其临床意义。方法采用酶联免疫吸附测定(ELISA)检测80例PTE患者(急性大面积PTE组20例、非大面积PTE组60例)、40名正常人(对照组)的血D-二聚体(D-D)、组织型纤溶酶原激活剂(t-PA)、纤溶酶原激活剂抑制物1(PAI-1)、血浆蛋白S(Ps)、血浆蛋白C(Pc)、凝血酶调节蛋白(TM)、抗心磷脂抗体(ACA)、同型半胱氨酸(Hcy)含量;采用发色底物法检测抗凝血酶Ⅲ活性(AT-Ⅲ)。结果急性大面积PTE组患者血D-D、t-PA、PAI-1、Ps、TM、含量分别为(1.46±0.62)mg/L、(11.4±6.9)μg/L、(88.2±27.5)μg/L、(22.40±9.40)mg/L、(6.8±1.1)μg/L,非大面积PTE组分别是(0.92±0.27)mg/L、(6.6±1.5)μg/L、(60.1±26.1)μg/L、(23.90±10.70)mg/L、(6.3±1.5)μg/L,均显著高于正常对照组的(0.38±0.10)mg/L、(4.7±1.4)μg/L、(35.7±9.2)μg/L、(16.10±6.20)mg/L、(3.0±0.5)μg/L(分别P<0.01、<0.05)。急性大面积PTE组患者血AT-Ⅲ含量为(86.0±11.8)%,非大面积PTE组为(90.1±9.0)%,显著低于正常对照组的(102.6±9.20)%(P分别<0.01、0.05)。两PET组患者ACA-IgG、IgM、IgA显著高于正常对照组,差异有统计学意义(P<0.05)。结论PTE患者存在凝血纤溶系统功能失衡和肺血管内皮损伤。     

CA 125 levels in patients with non-Hodgkin lymphoma and other hematologic malignancies

Cancer antigen (CA 125) is a glycoprotein commonly used as a tumor marker. In this study, CA 125 levels were measured in 149 patients and 26 healthy control subjects. The study group included 69 non-Hodgkin lymphomas (NHL), 25 Hodgkin disease (HD), 20 acute myelocytic leukemia (AML), 14 chronic lymphocytic leukemia (CLL), 12 chronic myelocytic leukemia (CML), and nine multiple myeloma (MM) patients. CA 125 was elevated in 37 of the patients and in none of the control subjects. Average CA 125 level in NHL patients was significantly higher than the controls (56.2 +/- 9.2 U/ml, 7.99 +/- 1.05 U/ml respectively) (P < 0.05). CA 125 levels were significantly higher in NHL patients with abdominal involvement (113.6 +/- 23.4 U/ml), with B-symptoms (72.3 +/- 13.2 U/ml), higher stage of the disease (stages III and IV -75.3 +/- 14.9 U/ml), bulky disease (99.9 +/- 30.4 U/ml) and in those with serosal involvement (103.1 +/- 18.5 U/ml) (P < 0.05 for all). CA 125 levels were also elevated in seven patients with HD and in a patient with CLL with pleural effusion. In conclusion, for patients with NHL, high levels of CA 125 were associated with B-symptoms, advanced stage, bulky disease, abdominal, and serosal involvement. Therefore, CA 125 might be used as a marker to predict prognosis and to detect advanced disease in NHL.     

Correction of hypozincemia following liver transplantation in children is associated with reduced urinary zinc loss

Zinc deficiency is a relatively common problem in children with chronic liver disease. We have previously shown inappropriate urinary zinc excretion in children with chronic liver disease and hypozincemia. This study was designed to determine if zinc deficiency and inappropriate urinary zinc losses are corrected in children with liver disease by liver transplantation. Thirty-three patients (age 1-19 years) underwent 35 liver transplants for acute and chronic liver disease. At the time of transplant, 17 patients had low plasma zinc (hypozincemic) (plasma zinc, 45.4 +/- 1.8 microg/dL), whereas 18 had normal plasma zinc (75.7 +/- 3.8). Before transplant, patients with zinc deficiency had higher urinary zinc to creatinine ratio compared with those with normal zinc status (6.6 +/- 1.9 vs. 2.2 +/- 0.6; P =.03) and lower serum albumin concentrations (low: 2.8 +/- 0.1 vs. normal: 3.3 +/- 0.2; P =.02). After transplant, there was a significant reduction in urinary zinc losses in the hypozincemic group followed by normalization of plasma zinc levels by 7 days posttransplant. These data suggest that the abnormal renal zinc homeostasis that is present in approximately 50% of pediatric patients undergoing liver transplant is rapidly improved and biochemical zinc deficiency is reversed after liver transplantation.     

The association of preoperative atrial fibrillation with post-cardiopulmonary bypass hyperfibrinolysis in rheumatic valvular heart disease patients

ObjectiveThe purpose of this study was to assess the fibrinolytic status after cardiopulmonary bypass in rheumatic valvular heart disease patients, and detect the associated factors of post-cardiopulmonary bypass hyperfibrinolysis.MethodsAccording to the fibrinolytic status after cardiopulmonary bypass, 203 rheumatic valvular heart disease patients were divided into two groups: hyperfibrinolysis group (H group, n = 78) and non-hyperfibrinolysis group (NH group, n = 125). The demographic characteristics, operative variables, and postoperative follow-ups were compared between these two groups.ResultsThe incidence of hyperfibrinolysis was 38.4% after cardiopulmonary bypass. Patients in the H group had a significant higher incidence of preoperative atrial fibrillation than patients in the NH group (92.3% vs. 55.2%, P < 0.01). Furthermore, postoperative daily drainage (655.3 ± 131.5 ml vs. 535.4 ± 161.4 ml, P < 0.01), transfusion volume of fresh frozen plasma (621.8 ± 220.2 ml vs. 455.2 ± 208.5 ml, P < 0.01), and red blood cells (5.9 ± 2.2 u vs. 4.7 ± 2.8 u, P < 0.01) was greater in the H group than in the NH group. Moreover, the logistic regression analysis revealed that preoperative atrial fibrillation was associated with post-cardiopulmonary bypass hyperfibrinolysis (OR = 19.691, 95% CI = 6.849–56.612; P < 0.05).ConclusionPreoperative artial fibrillation is associated with post-cardiopulmonary bypass hyperfibrinolysis in rheumatic valvular heart disease patients.     

Serum retinol binding protein 4 and nonalcoholic fatty liver disease in patients with type 2 diabetes mellitus

Retinol binding protein 4 (RBP4) is a protein secreted by adipocytes, and closely associated with insulin resistance. Whereas RBP4 is also mainly expressed in hepatocytes as the principal transport protein for retinol (vitamin A) in the circulation, and its pathophysiological role in liver remain unclear. The aim of this paper was to investigate the association between RBP4 and nonalcoholic fatty liver disease (NAFLD) in patients with type 2 diabetes mellitus (T2DM). Serum RBP4 and adiponectin concentrations were measured by radioimmunoassay in 52 diabetic patients who had NAFLD and 50 sex- and age-matched diabetic patients without any clinical features of liver diseases who had normal liver ultrasonic appearance and normal liver function. Serum RBP4 levels were elevated in diabetic patients with NAFLD (32.0+/-8.9 microg/ml vs. 41.3+/-9.8 microg/ml, p<0.001), while adiponectin decreased (17.4+/-9.3 microg/ml vs. 13.8+/-7.0 microg/ml, p=0.032). Male diabetic patients had higher serum RBP4 concentration and lower serum adiponectin concentration than female diabetic patients (38.5+/-9.9 microg/ml vs. 34.0+/-10.7 microg/ml, p=0.031 and 12.7+/-5.7 microg/ml vs. 20.23+/-9.8 microg/ml, p<0.001, respectively). Multiple logistic regression analysis revealed RBP4 and triglyceride as independent association factors for NAFLD, while the association between serum adiponectin and NAFLD was not significant. Increasing concentrations of RBP4 were independently and significantly associated with NAFLD in diabetic patients. In multiple linear regression analysis, alanine aminotransferase, fasting serum insulin and adiponectin were independent factors for serum RBP4 level. The study demonstrates that retinol binding protein 4 might contribute to the pathogenesis of nonalcoholic fatty liver disease.     

血栓调节蛋白和血管性血友病因子判断肝移植排斥反应的价值

目的 寻找早期诊断和监测肝移植排斥反应敏感和特异的实验室检查项目及指标。 方法 随机观察肝移植患者41例,其中出现排斥反应16例(急性排斥12例,慢性排斥4例)。在术前、术后隔天检测血浆可溶性血栓调节蛋白(STM)和血管性血友病因子(vWF)含量。 结果 有排斥者术后、排斥前2d、急性排斥后STM含量明显升高(分别为5.58 ng/ml ±0.42 ng/ml、5.93 ng/ml±0.45 ng/ml、7.88 ng/ml±0.29 ng/ml)和vWF含量亦明显升高(分别为101.2％±4.68％、104.3％±5.87％、127.7％±5.47％);在排斥反应的前2d,STM(5.93 ng/ml±0.45 ng/ml)和vwF(104.3％±5.87％)含量均明显升高;急性排斥较慢性排斥高(7.88 ng/ml±0.29 ng/ml与6.35 ng/ml±0.54 ng/ml,t=2.46,P<0.05)、冲击治疗无效组较有效组高(8.30 ng/ml±0.1 9 ng/ml与3.82 ng/ml±0.22 ng/ml,t=12.98,P<0.01)、治疗后死亡组较生存组高(7.98 ng/ml±0.18 ng/ml与6.51 ng/ml±0.41 ng/ml,t=3.39,P<0.01)。结论 STM和vWF可作为监测肝移植排斥的实验室项目和指标;STM含量不仅可作为肝移植排斥的早期预报指标,还适用于鉴别急、慢性排斥反应,并可作为冲击治疗疗效和判断预后的指标。     

Unchanged global fibrinolytic capacity during the course of hematopoietic stem cell transplantation.

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.