Bile acid-induced tissue factor activity in hepatocytes correlates with activation of farnesoid X receptor.

Bile acids (BA) have been found to promote coagulation by increasing tissue factor (TF) activity. The contribution of elevated BA levels and cholestasis to TF decryption within the liver parenchyma and the role of farnesoid X receptor (FXR) in this process remain unclear. We investigated the effects of BA on TF activity and thrombin generation in hepatocytes and correlated these effects with activation of FXR-dependent signaling and apoptosis.

Impact of electric cardioversion on platelet activation.

Introduction: Atrial fibrillation (AF) comes along with high risk of stroke. This risk continues even after re-establishing sinus rhythm with cardioversion. Aim of this study is to evaluate the contribution of electric cardioversion (EC) to platelet activation and procoagulatory tendency.

Increased tissue factor activity promotes thrombin generation at type 1 diabetes onset in children.

Objective: In type 1 diabetes (T1D), a prothrombotic status due to elevated coagulation factors coincides with metabolic derailment. In a previous study, we discovered altered thrombin generation profiles in children with T1D. These alterations are potentially most pronounced at T1D onset and ameliorated after insulin treatment.

New insights into neonatal coagulation: normal clot formation despite lower intra-clot thrombin levels.

Background: Healthy neonates exhibit no bleeding tendencies, but exhibit longer partial thromboplastin times than adults. Lower clotting factor levels may be balanced by lower inhibitor levels, which is not reflected in routine coagulation assays, but could result in normal clot formation in vivo. The novel thrombodynamics assay simulates a damaged vessel with tissue factor immobilized to a surface.

Neonatal thrombocytopenia: Thrombin generation in presence of reduced platelet counts and effects of rFVIIa in cord blood.

Healthy neonates exhibit a well-functioning haemostatic system despite peculiarities regarding composition of clotting factors and inhibitors as well as impaired platelet aggregation. Thrombocytopenia and severe bleeding events are feared in sick infants. Recombinant factor VIIa (rFVIIa) is a haemostatic agent used as a last resort in neonates with refractory bleedings.

Polyphosphate in Neonates: Less Shedding from Platelets and Divergent Prothrombotic Capacity Due to Lower TFPI Levels.

The neonatal hemostatic system exhibits a fragile balance featuring lower levels of clotting factors as well as inhibitors. Neonatal platelets show hypoaggregability, but neonates exhibit well-functioning primary and secondary hemostasis despite this impairment. Recently, polyphosphate shed by activated platelets has been shown to induce a prothrombotic shift on the plasmatic coagulation system of adults.

Non-enzymatic quantification of polyphosphate levels in platelet lysates and releasates.

Inorganic polyphosphate has been shown to be shed upon platelet activation inducing prothrombotic stimuli on the coagulation system. Several methods have been published to detect and quantify polyphosphate in various cells and tissues, but evaluation of platelet content has only been achieved by indirect detection of orthophosphate after enzymatic digestion, thus, relying heavily on specificity of an exopolyphosphatase that is not commercially available. We present a non-enzymatic method for quantification of platelet-derived polyphosphate featuring optimized extraction on silica spin-columns, followed by specific fluorescence detection using DAPI.

Thrombin generation before and after multicomponent blood collection.

Background: Apheresis technology has made tremendous progress up to the development of automated blood component collection, which offers increased efficiency in donor blood use, but the concern about the contact of donor blood with artificial surfaces remains. Activation of the hemostatic system is a major issue in this context and is controversial. The aim of this study was to estimate the effect of apheresis on continuous thrombin generation (TG), representing a new tool to examine the overall function of the plasmatic clotting system.

Clot strength: a comparison between cord and adult blood by means of thrombelastometry.

Objective: To evaluate the clot strength in cord versus adult blood.

Method: Thrombelastometry (TEM) was the method of choice as it provides information on the clot strength in terms of the maximum clot firmness (MCF) and on the fibrin polymerization process in terms of the clot formation time and the alpha angle.

Results: The MCFs were significantly lower in cord versus adult platelet rich plasma (PRP, 63.

Calibrated automated thrombin generation in normal uncomplicated pregnancy.

Pregnancy is associated with substantial changes in the haemostatic system and a six-fold higher incidence of venous thromboembolism. Conventional global tests, such as prothrombin time and activated partial thromboplastin time, do not definitely detect this hypercoagulable condition. We investigated whether the changes in haemostatic system during pregnancy are reflected in the calibrated automated thrombography (CAT).

Collagen/endogenous thrombin-induced platelet aggregation in whole blood samples.

The aim of the study was to investigate the individual and combined effects of collagen (3.5 microg/ml) and endogenously generated thrombin (due to addition of 0.35 pmol/l tissue factor) on platelet aggregation in the physiological environment of whole blood by means of the impedance method.

Ghrelin--an indicator for fat oxidation in obese children and adolescents during a weight reduction program.

The aim of this study was to investigate the effect of short-term energy restriction combined with physical activity on changes in substrate oxidation and changes in plasma concentrations of ghrelin. We designed a longitudinal intervention study of 4.2 MJ (= 1,000 kcal) daily with exercise.

High availability of intravascular tissue factor in neonates.

In the present study, we compared the levels of intravascular tissue factor (TF) present in cord versus adult whole blood (WB) prior and after lipopolysaccharide (LPS) stimulation. High levels of intravascular TF might help to explain the clinically observed efficient clotting of cord blood despite low levels of procoagulatory factors. Quantitative reverse transcription-polymerase chain reaction revealed same (basal) TF mRNA expression levels in both native cord and adult WB, and approximately same increase in TF mRNA expression owing to LPS incubation in both cord and adult WB (normalized to the housekeeping gene beta-actin).

Effects of beta2-glycoprotein-I on platelet aggregation in cord versus adult whole blood.

We present a peculiarity of the neonatal hemostatic system that might contribute to establish a procoagulant readiness in neonatal blood by sensitizing neonatal platelets for ADP stimulation. beta2-glycoprotein-I (beta2-GP-I) is a plasma constituent capable of suppressing ADP-induced platelet aggregation. We found significant lower levels of beta2-GP-I in cord vs.

Effects of melagatran on activated partial thromboplastin time and on ecarin clotting time in cord versus adult plasma.

Melagatran is the active form of the oral direct thrombin inhibitor ximelagatran. Melagatran does not require antithrombin as a cofactor. Its administration is therefore of special interest in neonatal patients, whose plasma is relatively deficient in antithrombin.

Anticoagulant action of melagatran: a comparison between neonates and adults using calibrated automated thrombography (CAT).

In the present study, we comparatively evaluated the anticoagulant efficacy of the new direct thrombin inhibitor melagatran in cord vs. adult plasma. In contrast to heparin, melagatran does not require antithrombin as a cofactor.

Protein S modulates the anticoagulant action of recombinant human activated protein C: a comparison between neonates and adults.

Recombinant human-activated protein C (rhAPC, Drotrecogin alpha (activated), Xigris) has been shown to reduce organ damage and decrease mortality in severe sepsis. Since protein S (PS) serves as a potentiating cofactor of activated protein C and since PS levels are low in neonatal plasma, we hypothesized that the anticoagulant effect of rhAPC would be decreased in cord plasma compared to adult plasma. We demonstrate that the anticoagulant action of 0.

An evaluation of the procoagulant action of recombinant activated factor VII in cord whole blood versus adult whole blood using thromboelastography.

Recombinant activated factor VII (rFVIIa) has been reported to be effective in adult patients in various clinical situations and might be beneficial in neonates with bleeding tendency. In the present study we compared the procoagulant action of increasing amounts of rFVIIa in both cord whole blood and adult whole blood with respect to changes in the values of the clotting time, clot formation time, and maximum clot firmness by means of thromboelastography. Thromboelastography allows evaluation of the effects of rFVIIa on haemostasis in whole blood.

Recombinant human activated protein C, heparin and melagatran in umbilical cord versus adult plasma.

Aim: We investigated the anticoagulant effects of recombinant human activated protein C (rhAPC), unfractionated heparin (UH) and melagatran (a new direct thrombin inhibitor [DTI]), when administered individually and in combinations of rhAPC with either UH or melagatran, in umbilical cord and adult plasma. rhAPC is a promising candidate treatment to improve the outcome of severe sepsis in neonates and adults; the DTI melagatran represents a potential advance in antithrombotic therapy.

Methods: The anticoagulant efficacy of these drugs was measured using the standard coagulation assays activated partial thromboplastin time (aPTT) and prothrombin time (PT).

Additive effects of anticoagulants: recombinant human activated protein C and heparin or melagatran, in tissue factor-activated umbilical-cord plasma.

Severe sepsis in children or adults may cause a life-threatening coagulopathy, with widespread consumption of activated protein C (APC); recombinant human APC (rhAPC) is a promising candidate anticoagulant treatment. We investigated the effects of rhAPC and other anticoagulants on coagulation triggered by adding small quantities of lipidated tissue factor to human umbilical-cord plasma in vitro. rhAPC, unfractionated heparin (UH), and melagatran (a direct thrombin inhibitor) were studied individually, and in combinations of rhAPC with either UH or melagatran.

Leptin responses to insulin administration in children with short stature.

Abstract The aim of the study was to investigate the effect of standard insulin tolerance test on plasma leptin levels in children with idiopathic short stature (ISS) and in children with growth hormone deficiency (GHD). Furthermore, plasma leptin levels were analyzed with regard to age, body mass index (BMI), and plasma levels of human growth hormone and of insulin-like growth factor-1 (IGF-1). Sixty-three patients with a height below the third percentile, an age of 10.

Drotrecogin alfa (activated, Xigris) in combination with heparin or melagatran: an in vitro investigation.

Background: The present in vitro study of human plasma investigated the anticoagulant effects of recombinant human activated protein C (rhAPC; drotrecogin alfa [activated, Xigris]), combined with either unfractionated heparin (UH) or the direct thrombin inhibitor melagatran.

Methods: Prolongation of clotting time and generation of prothrombin fragments 1 and 2 (F1 + 2) and of thrombin-antithrombin (TAT) complex were measured in vitro. Clot formation was induced by adding low levels (final concentration, 20 pmol/L) of lipidated tissue factor (TF) to citrated venous plasma samples from healthy human volunteers (n = 16).

Higher concentrations of heparin and hirudin are required to inhibit thrombin generation in tissue factor-activated cord plasma than in adult plasma.

Neonatal plasma clots slower than adult plasma, and only 30-50% of peak adult thrombin activity can be produced in neonatal plasma when high amounts of tissue factor (TF) are added to trigger clotting, as used in standard clotting assays. Plasma activation by addition of low amounts of TF probably better reflects conditions in vivo. Under these conditions, cord plasma clots faster than adult plasma.

Drotrecogin alfa activated (recombinant human activated protein C) in combination with heparin or melagatran: effects on prothrombin time and activated partial thromboplastin time.

Recombinant human activated protein C (rhAPC) has recently been demonstrated to be a promising candidate to improve the outcome for patients with severe sepsis. Plasma-derived activated protein C and unfractionated heparin (UH) exert anticoagulant synergy due to mechanisms that simultaneously decrease thrombin generation. Melagatran, a new direct thrombin inhibitor, does not bind to plasma proteins or requires antithrombin as a cofactor.

Anticoagulant action of melagatran, the active form of the oral direct thrombin inhibitor ximelagatran, in umbilical cord and adult plasma: an in vitro examination.

Introduction: This study was performed to compare the anticoagulant activity of melagatran, the active form of the oral direct thrombin inhibitor ximelagatran, in umbilical cord plasma with that in adult plasma. In contrast with the most frequently administered anticoagulants, the heparins, melagatran acts independently of antithrombin (AT). As a consequence, administration of melagatran is of special interest in neonates, who have physiologically low levels of AT.