N-terminal pro-brain natriuretic peptide and other risk markers for the separate prediction of mortality and subsequent myocardial infarction in patients with unstable coronary artery disease: a Global Utilization of Strategies To Open occluded arteries (GUSTO)-IV substudy.

Background: Biochemical markers are useful for prediction of cardiac events in patients with non-ST-segment-elevation acute coronary syndrome (ACS). The associations between N-terminal pro-brain natriuretic peptide (NT-proBNP) and other biochemical and clinical risk indicators, as well as their prognostic value concerning the individual end points of death and myocardial infarction (MI), were elucidated in a large cohort of ACS patients.

Methods And Results: NT-proBNP, troponin T, and C-reactive protein (CRP) were analyzed in blood samples obtained at a median of 9.

Low molecular weight heparin (dalteparin) compared to unfractionated heparin as an adjunct to rt-PA (alteplase) for improvement of coronary artery patency in acute myocardial infarction-the ASSENT Plus study.

Background: Current thrombolytic-antithrombotic regimens in acute myocardialinfarction (AMI) are limited by incomplete early coronary reperfusion and by reocclusion and reinfarction. We compared the effects of low molecular weight heparin (LMWH) versus unfractionated heparin (UFH) as an adjunct to recombinant tissue-plasminogen activator (alteplase) on coronary artery patency and clinical outcomes in AMI.

Methods: Patients with AMI treated with alteplase (n=439) were randomised to either subcutaneous dalteparin (120 IU/kg every 12h) for 4-7 days or intravenous infusion of UFH for 48 h.

Troponin and C-reactive protein have different relations to subsequent mortality and myocardial infarction after acute coronary syndrome: a GUSTO-IV substudy.

Objectives: We sought to evaluate C-reactive protein (CRP) and troponin T (TnT) as predictors of risk of the individual end points of mortality and myocardial infarction (MI) in a large cohort of patients with acute coronary syndrome (ACS).

Background: Both CRP and TnT predict risk of future coronary events in patients with ACS. However, the relationships between the levels of the markers and the individual end points are still unclear.

Cell adhesion and tissue factor upregulation in oxygenators used during coronary artery bypass grafting are modified by the Corline Heparin Surface.

Objective: Cardiopulmonary bypass (CPB) is associated with inflammatory response and activation of coagulation. We investigated the influence of a new heparin surface on the activation of cells retrieved from oxygenators used during coronary artery bypass grafting (CABG).

Design: Sixty patients undergoing CABG with CPB were randomly assigned to either uncoated or completely Corline Heparin Surface (CHS)-coated circuits with one of three different levels of systemic heparin: standard, high or low.

Tissue factor regulation and cytokine expression in monocyte-endothelial cell co-cultures: effects of a statin, an ACE-inhibitor and a low-molecular-weight heparin.

Introduction: Mounting evidence implies beneficial properties of statins and angiotensin converting enzyme (ACE)-inhibitors beyond those of their original indications in the treatment of coronary artery disease (CAD). Less is known of the mechanisms by which low-molecular-weight (LMW) heparin, also used in unstable CAD, affects the cellular micro-environment. The effects of these drugs in monocyte-endothelial cell co-culture systems have so far been sparsely investigated.

Myocardial damage, inflammation and thrombin inhibition in unstable coronary artery disease.

Aim: Unstable coronary artery disease (CAD) is a multifactorial disease involving both thrombotic and inflammatory processes. We have assessed the time-course and the influence of thrombin inhibitors on changes in fibrinogen and C-reactive protein levels, and their relation to myocardial ischaemia in unstable CAD.

Methods And Results: Three hundred and twenty patients were randomized to 72 h infusion with three different doses of inogatran, a direct thrombin inhibitor, or unfractionated heparin.

[Prophylaxis of postoperative thromboembolism. New alternatives to low-molecular-weight heparin].

For somewhat more than a decade low molecular weight heparins have dominated in the pharmacological prevention of postoperative venous thromboembolism. At present there are some new methods of potential interest both as prophylactic substances but also to better understand the pathophysiology of deep vein thrombosis. These are inhibition of factor VII a/tissue factor complex (NAP, Nematode Anticoagulant Protein), inhibition of activated factor X (the synthetic pentasaccharide fondaparinux) and thrombin inhibition (melagatran and its oral prodrug ximelagatran).

Coagulation, fibrinolysis, and cell activation in patients and shed mediastinal blood during coronary artery bypass grafting with a new heparin-coated surface.

Objectives: Heparin coating of the cardiopulmonary bypass circuit is shown to improve the biocompatibility of the surface. We have studied a new heparin surface, the Corline Heparin Surface, applied to a complete set of an extracorporeal device used during coronary artery bypass grafting in terms of activation of inflammation, coagulation, and fibrinolysis in patients and in shed mediastinal blood.

Methods: Sixty patients scheduled for coronary artery bypass grafting were randomized to one of 3 groups with heparin-coated devices receiving either a standard, high, or low dose of systemic heparin or to an uncoated but otherwise identical circuit receiving a standard dose of systemic heparin.

Influence on coagulation activity by subcutaneous LMW heparin as an adjuvant treatment to fibrinolysis in acute myocardial infarction.

In this study, which includes 101 patients with acute ST segment-elevated myocardial infarction, we investigated the influence on the increased coagulation activity after streptokinase treatment by adding low-molecular-weight (LMW) heparin or placebo and the relation between the coagulation activity and ischemic episodes, coronary patency, and mortality. The expected increase of prothrombin fragment 1+2 (F1+2), thrombin-antithrombin (TAT), and D-dimer were significantly attenuated at 2, 6, and 18 h (D-dimer only at 18 h) in the dalteparin group compared to placebo. Ischemic episodes during the first 24 h appeared significantly more often in patients with F1+2 levels above the median at 18 h.

Relationship between interleukin 6 and mortality in patients with unstable coronary artery disease: effects of an early invasive or noninvasive strategy.

Context: Inflammatory activity is associated with high rates of long-term mortality in unstable coronary artery disease (CAD). Interleukin 6 (IL-6) induces C-reactive protein and fibrinogen, systemic markers of inflammation.

Objectives: To determine whether plasma levels of IL-6 are predictive of mortality and to evaluate the interaction of IL-6 levels with the effects of invasive vs noninvasive treatment strategies in unstable CAD patients.

Blood cell activation, coagulation, and inflammation in men and women with coronary artery disease.

We investigated in some detail the immunologic and procoagulant activation patterns in men and women with unstable (UA, n=26) versus stable (SA, n=40) coronary artery disease (CAD). Leukocyte activation and platelet-leukocyte complex formation were assessed by flow cytometry. Plasma markers of coagulation and inflammation were analyzed.

Coagulation and fibrinolysis in chronic venous insufficiency.

Background: Varicose veins (VV) are common, but only some patients will develop chronic venous insufficiency (CVI) with skin changes or venous ulcer. The pathophysiology of venous ulcer development is complex, and may involve abnormalities in coagulation, fibrinolysis and proinflammatory cytokines. The purpose of this study was to correlate plasma markers within these systems and skin pathology.

Coagulation activity and clinical outcome in unstable coronary artery disease.

In the current study, we investigated molecular markers of coagulation activity, ie, prothrombin fragment 1+2 (F1+2), thrombin-antithrombin (TAT) complex, soluble fibrin (SF), and D-dimer, and their relation to death, myocardial infarction, and refractory angina during and after anticoagulant treatment in unstable coronary artery disease. Patients with unstable coronary artery disease (N=320) were randomized to a 72-hour infusion with either inogatran, a low-molecular-mass direct thrombin inhibitor, or unfractionated heparin. During the 30-day follow-up, a 40% lower event rate was seen in patients with high compared with low baseline levels of TAT or SF.

Cellular consequences upon factor VIIa binding to tissue factor.

Tissue factor (TF) is a cell-surface-bound glycoprotein that binds the zymogen, factor (F) VII, and the active serine protease, FVIIa. The FVIIa/TF complex is the major activator of coagulation in vivo. Under normal physiological conditions, TF is expressed only on extravascular sites and perivascularly in the adventitial layer of blood vessels.

Binding of factor VIIa to tissue factor on human fibroblasts leads to activation of phospholipase C and enhanced PDGF-BB-stimulated chemotaxis.

Tissue factor (TF) is the cellular receptor for factor FVIIa (FVIIa), and the complex is the principal initiator of blood coagulation. The effects of FVIIa binding to TF on cell migration and signal transduction of human fibroblasts, which express high amounts of TF, were studied. Fibroblasts incubated with FVIIa migrated toward a concentration gradient of PDGF-BB at approximately 100 times lower concentration than do fibroblasts not ligated with FVIIa.

Markers of myocardial damage and inflammation in relation to long-term mortality in unstable coronary artery disease. FRISC Study Group. Fragmin during Instability in Coronary Artery Disease.

Background: In patients with unstable coronary artery disease, there is a relation between the short-term risk of death and blood levels of troponin T (a marker of myocardial damage) and C-reactive protein and fibrinogen (markers of inflammation). Using information obtained during an extension of the follow-up period in the Fragmin during Instability in Coronary Artery Disease trial, we evaluated the usefulness of troponin T, C-reactive protein, and fibrinogen levels and other indicators of risk as predictors of the long-term risk of death from cardiac causes.

Methods: Levels of C-reactive protein and fibrinogen at enrollment and the maximal level of troponin T during the first 24 hours after enrollment were analyzed in 917 patients included in a clinical trial of low-molecular-weight heparin in unstable coronary artery disease.

Role of platelet P-selectin and CD40 ligand in the induction of monocytic tissue factor expression.

Activated platelets can express CD40 ligand (CD40L) and trigger inflammatory response and tissue factor (TF) expression in endothelial cells through interaction with CD40. This pathway is also important for T cell-induced monocyte and endothelial cell procoagulant activity. We have studied the potential role of the CD40-CD40L pathway in platelet-induced TF expression in a monocytic cell line and in whole-blood monocytes.

Coagulation activation after laparoscopic cholecystectomy in spite of thromboembolism prophylaxis.

Background: The aim of this study was to determine whether laparoscopic cholecystectomy (LC), in spite of its minimally invasive nature, causes coagulation activation.

Methods: Sixty-four patients undergoing LC were included prospectively. All received either dextran or low-molecular-weight heparin (LMWH).

Markers of hypercoagulation and von Willebrand factor in postmenopausal women with unstable coronary artery disease. Discriminatory ability regarding unstable coronary artery disease and coronary atherosclerosis using receiver operating characteristics.

Objectives: Many women with typical anginal chest pain have normal coronary angiograms. The pathogenetic mechanisms behind the chest pain in these patients are unknown but may be due to increased thrombogenicity. We evaluated markers of hypercoagulation and thrombosis in women with clinical signs of unstable coronary artery disease (CAD).

Haemostasis in patients with Behçet's disease.

Aim: to determine whether Behçet's disease affects haemostatic function.

Setting: University Hospital, Turkey.

Patients: one hundred and twenty-seven consecutive patients with Behçet's disease, 34 of whom with a history of vascular involvement.

The role of RAR and RXR activation in retinoid-induced tissue factor suppression.

Excessive expression of tissue factor (TF) is a common finding in leukaemic cells and may contribute to thrombotic complications in patients. Retinoic acid has been shown to induce differentiation and reduce TF expression in acute promyelocytic leukaemia (APL) cells in vitro, and to induce remission in APL patients. Treatment of the APL cell line NB4 with the specific retinoic acid receptor-alpha (RARalpha) agonists Ro4-6055 or TTNPB resulted in down-regulation of TF expression and in induction of differentiation.

Heparin-coated cardiopulmonary bypass circuits reduce circulating complement factors and interleukin-6 in paediatric heart surgery.

Children are sensitive to the inflammatory side effects of cardiopulmonary bypass (CPB). Our intention was to investigate if the biocompatibility benefits of heparin-coated CPB circuits apply to children. In 20 operations, 19 children were randomized to heparin-coated (group HC, n = 10) or standard (group C, n = 10) bypass circuits.

No benefit of reduced heparinization in thoracic aortic operation with heparin-coated bypass circuits.

Background: Heparin coating of the cardiopulmonary bypass circuit attenuates inflammatory response and confer clinical benefits in cardiac operations. The positive effects may be amplified with reduced systemic heparin dosage. We studied markers of inflammation and coagulation in thoracic aortic operations with heparin-coated circuits and standard vs reduced systemic heparinization.

Coagulation and fibrinolysis after open infrarenal abdominal aortic aneurysm repair in a long-term perspective.

In patients with abdominal aortic aneurysms (AAA) the coagulation and fibrinolytic systems have been found to be activated preoperatively. Does the increased activity of the coagulation and fibrinolytic systems persist after AAA surgery in a long-term perspective? Prothrombin fragment 1+2 (F1+2), thrombin-antithrombin complex (TAT), tissue plasminogen activator (tPA), human plasminogen activator inhibitor type 1, and human cross-linked fibrin degradation product (D-dimer) were analysed in 18 patients after open AAA surgery (postop-AAA). The median time between surgery and blood sampling was 19 months (range, 5-37 months).

Activated partial thromboplastin time and clinical outcome after thrombin inhibition in unstable coronary artery disease.

Unlabelled: Aims Direct thrombin inhibitors have failed to prove superiority over unfractionated heparin in several clinical trials of unstable coronary artery disease. We have investigated the relationship between activated partial thromboplastin time levels and adverse clinical events, i.e.