Pharmacodynamics assessment of Bemiparin after multiple prophylactic and single therapeutic doses in adult and elderly healthy volunteers and in subjects with varying degrees of renal impairment.

Introduction: Aging and renal impairment may prolong the half-life and lead to accumulation of low molecular weight heparins. Correct dosing is critical to prevent bleeding or thrombosis.

Materials And Methods: Open, parallel study.

A genome-wide association study identifies KNG1 as a genetic determinant of plasma factor XI Level and activated partial thromboplastin time.

Objective: Elevated plasma levels of coagulation factor XI (FXI) are implicated in the pathogenesis of venous thromboembolism and ischemic stroke, and polymorphisms in the F11 gene are associated both with risk of venous thromboembolism and an elevated plasma FXI level.

Methods And Results: Here, we report the first hypothesis-free genome-wide genetic analysis of plasma FXI levels. Two genome-wide significant loci were detected in the family-based Genetic Analysis of Idiopathic Thrombophilia 1 cohort: one located in the kininogen 1 gene (KNG1) (rs710446; P=7.

A genome-wide association study of the Protein C anticoagulant pathway.

The Protein C anticoagulant pathway regulates blood coagulation by preventing the inadequate formation of thrombi. It has two main plasma components: protein C and protein S. Individuals with protein C or protein S deficiency present a dramatically increased incidence of thromboembolic disorders.

Safety assessment and pharmacodynamics of a novel ultra low molecular weight heparin (RO-14) in healthy volunteers--a first-time-in-human single ascending dose study.

Introduction: RO-14 is a novel ultra low molecular heparin. The purpose of this study was to evaluate the safety and pharmacodynamic profile of RO-14 in healthy males.

Materials And Methods: We conducted a two-stage, single-center, open-label, randomized study.

Hemostatic proteins and their association with hematoma growth in patients with acute intracerebral hemorrhage.

Background And Purpose: We tested the hypothesis that proteins of hemostasia could be associated with hematoma growth (HG) in patients with acute intracerebral hemorrhage.

Methods: We prospectively studied patients with spontaneous supratentorial intracerebral hemorrhage within the first 6 hours after the onset of symptoms. HG was defined as an increase > 33% in the volume of hematoma on CT obtained 24 to 72 hours after the onset of symptoms in comparison with the CT obtained at admission.

Newly diagnosed versus relapsed idiopathic thrombotic thrombocytopenic purpura: a comparison of presenting clinical characteristics and response to treatment.

The remission rate with plasma exchange (PE) in thrombotic thrombocytopenic purpura (TTP) exceeds 80%, but the disease relapses in up to 20-30% of the cases. Clinical characteristics and response to treatment of relapsed TTP are not well defined. The objective of the present study was to compare the clinical and biological characteristics at presentation and the response to treatment between de novo and relapsed TTP.

A genome-wide exploration suggests an oligogenic model of inheritance for the TAFI activity and its antigen levels.

Thrombin-Activatable Fibrinolysis Inhibitor (TAFI) is a protein that potently attenuates fibrinolysis. A considerable proportion of its variability levels is genetically determined. It has been associated with arterial and venous thrombosis.

Change in hemostatic markers after recombinant tissue-type plasminogen activator is not associated with the chance of recanalization.

Background And Purpose: We evaluated the association between recombinant tissue-type plasminogen activator recanalization and change in hemostatic markers.

Methods: We studied 40 patients. Recanalization was measured with transcranial Doppler.

Patent foramen ovale and prothrombotic markers in young stroke patients.

Patent foramen ovale (PFO) is more frequent in cryptogenic stroke patients than in the general population. The aim of this study was to determine prothrombotic markers regarding PFO in young cryptogenic stroke patients. We prospectively included consecutive cryptogenic stroke patients younger than 55 years.

Postprandial thrombin activatable fibrinolysis inhibitor and markers of endothelial dysfunction in type 2 diabetic patients.

The aim of this study was to assess postprandial changes in thrombin activatable fibrinolysis inhibitor (TAFI) antigen, a thrombin-dependent fibrinolysis inhibitor with anti-inflammatory properties, and soluble markers of endothelial dysfunction in normotriglyceridemic type 2 diabetic patients. Fasting and postprandial TAFI antigen, thrombomodulin, tissue factor pathway inhibitor (TFPI), and plasminogen activator inhibitor 1 were assessed in 12 normotriglyceridemic type 2 diabetic patients treated with diet (hemoglobin A1c, 6.80% +/- 0.

Pretreatment hemostatic markers of symptomatic intracerebral hemorrhage in patients treated with tissue plasminogen activator.

Background And Purpose: Symptomatic intracerebral hemorrhage (ICH) is a major complication of thrombolysis in patients with acute ischemic stroke. We analyzed whether baseline hemostatic markers could predict symptomatic ICH (SICH).

Methods: In a multicenter study of patients treated with intravenous tissue plasminogen activator (t-PA) within 3 hours of stroke onset, we analyzed the following variables: demographic data, vascular risk factors, blood glucose at admission, time from the onset of symptoms to t-PA infusion, blood pressure, neurological deficit measured by the National Institutes of Health Stroke Scale (NIHSS) score, early signs of ischemia on the baseline computed tomography (CT) scan, and protocol deviations.

Association of functional thrombin-activatable fibrinolysis inhibitor (TAFI) with conventional cardiovascular risk factors and its correlation with other hemostatic factors in a Spanish population.

Our aim was to determine the associations of functional thrombin-activatable fibrinolysis inhibitor (TAFI) levels in plasma with conventional cardiovascular risk factors, sex and age, and possible correlations with other hemostatic factors in a Spanish population. We included 303 individuals from a Spanish population. Hemostatic factors such as von Willebrand Factor, VII ag, VIIIc, XIc, XIIc, APCR, protein S, protein C, antithrombin, fibrinogen, and t-PA antigen were assayed.

Risk of acute coronary artery disease associated with functional thrombin activatable fibrinolysis inhibitor plasma level.

To our knowledge, there is little information about functional thrombin activatable fibrinolysis inhibitor (TAFI) levels and the risk of acute coronary artery disease (CAD). We investigated the risk of acute CAD related to plasma levels of functional TAFI. We found that functional TAFI levels in plasma (above 126%), increased the risk of acute CAD almost 4-fold.

Association after linkage analysis indicates that homozygosity for the 46C-->T polymorphism in the F12 gene is a genetic risk factor for venous thrombosis.

In a family-based study called GAIT (Genetic Analysis of Idiopathic Thrombophilia) that included a genome-wide scan we demonstrated that a polymorphism (46C-->T) in the F12 locus jointly influences variability of plasma (Factor XII) FXII levels and susceptibility to thrombotic disease. It then became germane to determine the prevalence of the 46C-->T polymorphism and its relative risk of thrombotic disease. We followed up evidence for genetic linkage with a case-control study, including 250 unrelated consecutive Spanish patients suffering from venous thrombotic disease and 250 Spanish subjects matched for sex and age as a controls.

A quantitative trait locus influencing free plasma protein S levels on human chromosome 1q: results from the Genetic Analysis of Idiopathic Thrombophilia (GAIT) project.

Objective: Protein S (PS) is a component of the protein C anticoagulant system. PS deficiency is associated with myocardial infarction and venous thromboembolism, two highly prevalent causes of death in industrialized nations. As part of the Genetic Analysis of Idiopathic Thrombophilia (GAIT) project, we conducted a genome-wide linkage screen to localize genes influencing variation in free PS (fPS) plasma levels.

Multicentre evaluation of IL Test Free PS: a fully automated assay to quantify free protein S.

Deficiency of the anticoagulant vitamin K-dependent protein S (PS) is associated with increased risk of venous thrombosis. In human plasma, PS circulates in two forms: as free protein (free PS) and PS bound to C4b-binding protein (C4BP), a regulator of the complement system. Assays for free PS have higher sensitivity and specificity for protein S deficiency than assays for total protein S.

A new locus on chromosome 18 that influences normal variation in activated protein C resistance phenotype and factor VIII activity and its relation to thrombosis susceptibility.

Activated protein C resistance (APCR) is the most prevalent risk factor for thrombosis, accounting for 20% to 60% of familial thrombophilia. A mutation in the F5 gene, factor V Leiden (FVL), is a major determinant of pathological APCR in some populations. However, APCR predicts risk for thrombosis independently of FVL.

Thromboplastin-thrombomodulin-mediated time: a new global test sensitive to protein S deficiency and increased levels of factors II, V, VII and X.

Background And Objectives: A new test for screening the procoagulant capacity of plasma is described and evaluated. This test is based on the coagulation of plasma initiated by thromboplastin (Tp) in the presence of thrombomodulin (TM). In a previous paper we reported that this test had a significant phenotypic and genetic correlation with thrombosis susceptibility.

Thromboplastin-thrombomodulin-mediated time and serum folate levels are genetically correlated with the risk of thromboembolic disease: results from the GAIT project.

The GAIT (Genetic Analysis of Idiopathic Thrombophilia) Project is a family-based study dedicated to elucidating the genetic basis of hemostasis-related phenotypes and thrombosis risk. In this paper, we have examined several lesser-studied hemostasis-related phenotypes in the 21 GAIT families: levels of vitamin B 12, serum folate, whole blood folate, alpha2-antiplasmin, prekallikrein, beta2-glycoprotein I, soluble P-selectin, factor XIII A and B subunits and a new coagulation measurement based on thromboplastin time in the presence or absence of thrombomodulin. Using the variance component method, we estimated the relative contributions of genetic and environmental influences on these phenotypes.

A quantitative-trait locus in the human factor XII gene influences both plasma factor XII levels and susceptibility to thrombotic disease.

One approach to the identification of genetic loci that influence complex diseases is through the study of quantitative risk factors correlated with disease susceptibility. Factor XII (FXII) plasma levels, a related phenotype correlated with thrombosis, is such a risk factor. We conducted the first genomewide linkage screen to localize genes that influence variation in FXII levels.