Tissue Plasminogen Activator Antigen Concentrations Research Articles

Prospective study of the incidence and predictors of thrombus in children undergoing palliative surgery for single ventricle physiology.

To determine the incidence and clinical and biomarker predictors of perioperative thrombosis in children with single ventricle physiology undergoing staged palliation. Nineteen patients were enrolled and 16 completed the study. Serial ultrasounds of the central venous system were performed to evaluate for thrombus. Plasma antithrombin III, thrombin-antithrombin complex, protein C, protein S, tissue factor pathway inhibitor, plasminogen activator inhibitor-1, tissue plasminogen activator antigen, D-dimer, soluble CD40 ligand, and urinary thromboxane were measured serially before and after surgery. Cardiopulmonary bypass time, aortic cross clamp time, blood product administration, inotrope score, chest tube output, cardiac function by echocardiography, intensive care unit and hospital lengths of stay, and central venous catheter days were recorded. The incidence of perioperative thrombus was 31%. Patients who developed a thrombus had poorer preoperative ventricular function (p = 0.03) and longer cardiopulmonary bypass times (p = 0.03) than those who did not develop a thrombus. Preoperative plasma antithrombin III was lower (p = 0.01) and tissue plasminogen activator antigen concentrations were higher (p = 0.02) in patients with a thrombus compared with patients without a thrombus. When measured over time, antithrombin III remained lower (p = 0.002) and tissue plasminogen activator antigen higher (p = 0.005) in those who developed a thrombus compared with those who did not. There were no other statistically significant differences in biomarkers of coagulation between patients with and without thrombosis. One-third of patients undergoing palliative surgery for single ventricle physiology develop thrombosis. Decreased ventricular function, low antithrombin III, and increased tissue plasminogen activator may predict those most suitable for randomized clinical trials of anticoagulation.

Specific elevation in plasma tissue plasminogen activator antigen concentrations in South Asians relative to Europeans

Elevated levels of haemostatic factors including tissue plasminogen activator (t-PA) antigen are associated with coronary heart disease in Europeans but data in South Asians are sparse. We performed a cross-sectional study of 111 healthy men and women aged 40-55 years (56 European and 55 Asian) frequency matched across a wide range of body mass index (17-34 kg/m2). All subjects had detailed adiposity and metabolic measurements, and five haemostatic factors were determined. South Asians had greater insulin resistance than Europeans (fasting insulin geometric mean, 7.1 versus 4.7 microU/ml, and 2-h insulin, 37.3 versus 14.1 microU/ml, respectively). There were no significant ethnic differences in the mean concentrations of fibrinogen, factor VII, von Willebrand factor, or fibrin D-dimer (P > 0.10). However, the t-PA antigen concentration was significantly elevated in South Asians compared with Europeans (mean, 10.6 versus 8.2 ng/ml, P = 0.001). t-PA correlated positively in both ethnic groups with features of the metabolic syndrome but the ethnic difference in t-PA persisted after adjustment for adiposity, metabolic and inflammatory variables (beta = 2.0, 95% confidence interval = 0.5-3.6, P = 0.012). We therefore hypothesize that elevated t-PA antigen may be a novel mechanism contributing to increased cardiovascular risk in South Asians.

Massive Fibrin Formation with Consecutive Impairment of Fibrinolysis in Patients with Out-of-Hospital Cardiac Arrest

Hypoxia and ischaemia influence blood coagulation and fibrinolysis. This study has been made to determine whether human cardiopulmonary arrest causes fibrin formation and reduction of fibrinolysis. Serial levels of fibrinopeptide A (FPA), fibrinopeptide B beta 15-42 (FPB beta 15-42), D-dimer, tissue plasminogen activator antigen concentration (t-PA antigen), t-PA activity, plasminogen activator inhibitor-1 antigen concentration (PAI-1 antigen), and PAI-1 activity were determined in 63 patients with out-of-hospital cardiopulmonary arrest. In the resuscitated patients, the markedly elevated FPA (194.8 +/- 54.2 ng/ml) at the beginning of cardiopulmonary resuscitation (CPR) significantly decreased to 32.4 +/- 9.1 ng/ml at 24 h after admission (p < 0.01), however, this was still about 20 times that of the normal controls. FPB beta 15-42 and D-dimer increased from the start of CPR to 60 min (189.3 +/- 97.4 ng/ml; p < 0.01 and 7726 +/- 3556 ng/ml; p < 0.001, respectively), and then decreased at 24 h after arrival at the Emergency Department (40.4 +/- 11.1 ng/ml and 5434 +/- 1049 ng/ml, respectively). At 30 min after arrival, FPA and FPB beta 15-42 significantly differed between the resuscitated patients and the patients who died (p < 0.001 and P < 0.05, respectively). Although t-PA antigen and t-PA activity was elevated at the time of arrival, 24 h thereafter, no-t-PA activity was detected. At 24 h after admission, PAI-1 antigen and PAI-1 activity were significantly increased (472.2 +/- 145.5 ng/ml; p < 0.001 and 103.6 +/- 36.1 IU/ml; p < 0.001, respectively). In conclusion, during and after CPR in patients with out-of-hospital cardiac arrest, massive fibrin generation with consecutive impairment of fibrinolysis were observed. These fibrin-mediated events may have some role in the derangement of vital organ function after cardiac arrest.

Hypercoagulability following Multiple Trauma

We sought evidence of hypercoagulability in 59 seriously injured trauma patients. An extended coagulation profile (consisting of tissue plasminogen activator antigen concentration, plasminogen activator inhibitor, serum antithrombin III, protein C antigen, functional protein C, protein S antigen, D-dimer, and prothrombin fragment 1.2) was compared to control values. Laboratory evidence of hypercoagulability was seen in 85% (n = 50) of the patients. Patients with an Injury Severity Score (ISS) > or = 16 (n = 36) had significantly elevated levels of D-dimer and decreased levels of functional protein C compared to patients with an ISS < or = 15 (n = 23). Functional protein C had a negative correlation (r = -0.44; p < 0.001) with the ISS. A hypercoagulable state exists immediately following severe trauma. Greater injury severity may increase this hypercoagulable state. Decreased levels of functional protein C best correlated with increased injury severity.

Insulin treatment improves microalbuminuria and other cardiovascular risk factors in patients with type 2 diabetes mellitus.

Insulin treatment of patients with type 2 diabetes causes hyperinsulinaemia and improves glycaemic control. We have studied how this affects risk factors for cardiovascular disease. Patients with secondary failure to oral hypoglycaemic agents were studied whilst still taking oral agents and after insulin treatment for 8 weeks in an open study. Department of Internal Medicine, University Hospital, Linköping. Ten consecutive patients with type 2 diabetes and secondary failure to oral hypoglycaemic agents. Switching oral treatment to insulin treatment. Effect on several cardiovascular risk factors. Fasting and postprandial plasma insulin concentrations were increased by insulin treatment whereas C-peptide concentrations were lowered. HbA1c was reduced from 8.9 +/- 0.3% (mean +/- SEM) to 6.3 +/- 0.2% after 8 weeks. There was a weight gain of 2.8 +/- 0.7 kg. Plasma concentrations of total- and very-low-density-lipoprotein (VLDL) cholesterol, VLDL-, low density lipoprotein and high-density-lipoprotein triglycerides were all reduced. The plasma concentration of apolipoprotein B was also lowered. Tissue plasminogen activator antigen measured after venous occlusion showed a significant reduction whilst plasminogen activator inhibitor 1 activity was 26.0 +/- 9.8 IU ml-1 on oral treatment and 18.2 +/- 4.7 IU ml-1 on insulin treatment (NS). Albumin excretion in the urine was reduced and the percentage reduction correlated with the percentage lowering of the tissue plasminogen activator antigen concentration after venous occlusion but not with the percentage change of basal tissue plasminogen activator antigen concentration. Insulin treatment of patients with type 2 diabetes and secondary failure to oral hypoglycaemic agents causes hyperinsulinaemia and improves or has no unfavourable effect on several cardiovascular risk factors.

Posttrauma coagulation and fibrinolysis

To determine the effects of disseminated intravascular coagulation (DIC) and head injury on posttrauma coagulation and fibrinolysis. Case-control study. General ICU (tertiary care center) in a city hospital serving a population of 150 million people. Forty trauma victims: 15 with DIC; 25 without DIC. Measurement of six types of coagulation and fibrinolytic molecular markers (fibrinopeptide A, fibrinopeptide B beta 15-42, plasmin antiplasmin complex, D-dimer, tissue plasminogen activator antigen concentration, tissue plasminogen activator activity) immediately after trauma, 3 days later, and 6 days later. Anticoagulant treatment with gabexate mesilate at 1.45 +/- 0.06 mg/kg/hr. Fibrinopeptide A, fibrinopeptide B beta 15-42, plasmin antiplasmin complex, and D-dimer showed high values immediately after trauma and exceeded normal activity for the first 6 days. When trauma was complicated with DIC, the molecular markers showed significantly higher values than those for non-DIC patients on all days. In the head-injured patients, such effect was not noted. Tissue plasminogen activator antigen concentration and tissue plasminogen activator activity were within a normal physiologic range of variation. By contrast, tissue plasminogen activator antigen concentration increased significantly after trauma in patients with DIC. When anticoagulant treatment was found effective, it caused a reduction in fibrinopeptide A. a) Fibrinolytic shut-down and its reactivation cannot be confirmed after trauma. b) Head injury does not lead to an increase in posttrauma coagulation or fibrinolytic activity. c) DIC enhances posttrauma coagulation and fibrinolytic activity and plasminogen activator inhibitor activity can be inferred in DIC patients. d) Increase in tissue plasminogen activator antigen concentration without tissue plasminogen activator activation may be a prognostic factor indicative of DIC and its chances of improvement, and fibrinopeptide A as an assessment criterion for the effectiveness of anticoagulant treatment.

Tissue plasminogen activator and other risk factors as predictors of cardiovascular events in patients with severe angina pectoris

The value of measurements of the fibrinolytic factors, tissue plasminogen activator and plasminogen activator inhibitor, for predicting death and non-fatal cardiovascular events was studied in 213 consecutive patients with angiographically documented coronary artery disease. In the course of 4-year follow-up, 47 patients (22.1%) had at least one cardiovascular event. We found the incidence of cardiovascular events to be positively associated with high tissue plasminogen activator antigen concentration, in addition to previous myocardial infarction, low ejection fraction, hypertension, high body mass index and high triglyceride levels. Cholesterol was not found to be associated with cardiovascular events. A high concentration of tissue plasminogen activator antigen thus implies an increased risk of cardiovascular events in patients with severe angina pectoris.

Two different mechanisms in patients with venous thrombosis and defective fibrinolysis: low concentration of plasminogen activator or increased concentration of plasminogen activator inhibitor.

Fibrinolytic components after venous occlusion and concentrations of tissue plasminogen activator inhibitor were studied in 100 consecutive patients with confirmed recurrent deep vein thrombosis or pulmonary embolism. After 20 minutes of venous occlusion the fibrinolytic response was decreased in 33 patients, as measured both amidolytically with S-2251 and on fibrin plates. Two different mechanisms responsible for the poor fibrinolytic response could be distinguished. Twenty two of the patients in whom the response was poor released normal amounts of tissue plasminogen activator antigen, as assayed by immunoradiometric assay, but had appreciably increased concentrations of tissue plasminogen activator inhibitor. The 11 other patients in whom the response was poor had both low tissue plasminogen activator activities and low tissue plasminogen activator antigen concentrations but normal concentrations of tissue plasminogen activator inhibitor. The results show not only that defective synthesis or release of tissue plasminogen activator may be important in the pathogenesis of venous thrombosis but also that a large group of patients with thrombosis have an increased concentration of the inhibitor to tissue plasminogen activator.