[Analysis with viscoelastic hemostatic assays - a guide]. / En guide till koagulationsanalys med viskoelastiska instrument.

Viscoelastic hemostasis analyses (VHA) are a complement in the evaluation of hemostasis in patients with major bleeding. The analysis measures viscoelastic changes in whole blood and the results give an overview of several components of hemostasis. VHA can be used to optimize fibrinogen levels, platelet and plasma substitution. The main clinical evidence supporting this strategy is in trauma, obstetric bleeding, heart and liver surgery, where algorithms based on VHA results facilitate individualized therapy. VHA measurement is of limited value to exclude treatment with anticoagulants and platelet inhibitors. Quality control aspects are also more cumbersome since whole blood with limited sustainability is used. Newer, more automated versions of the instruments have increased the reproducibility. The main advantage of VHA is the fast turn-around time and their role in guiding treatment in an emergency situation with bleeding.

Radiation Response of Large-Area 4H-SiC Schottky Barrier Diodes.

We report on the effects of large-area 4H-SiC Schottky barrier diodes on the radiation response to ionizing particles. Two different diode areas were compared: 1 mm × 1 mm and 5 mm × 5 mm. 6LiF and 10B4C films, which were placed on top of the diodes, were used as thermal neutron converters. We achieved a thermal neutron efficiency of 5.02% with a 6LiF thermal neutron converter, which is one of the highest efficiencies reported to date. In addition, a temperature-dependent radiation response to alpha particles was presented. Neutron irradiations were performed in a JSI TRIGA dry chamber and an Am-241 wide-area alpha source was used for testing the alpha response of the 4H-SiC Schottky barrier diodes.

Hemostatic effects of a dextran-based priming solution for cardiopulmonary bypass: A secondary analysis of a randomized clinical trial.

INTRODUCTION: Intravascular fluids administered to patients may influence hemostasis. In patients undergoing cardiac surgery with cardiopulmonary bypass, the heart-lung machine is primed with 1300 ml of fluid. We assessed postoperative coagulation and platelet function in patients randomized to two different priming solutions, one colloid-based (dextran 40) and one crystalloid-based. MATERIALS AND METHODS: Eighty-four elective cardiac surgery patients were randomized to either a dextran-based prime or Ringer's acetate with added mannitol. Blood samples were collected before, and 2 and 24 h after cardiopulmonary bypass. Coagulation was assessed by standard coagulation tests and rotational thromboelastometry. Platelet function was assessed with impedance aggregometry. Bleeding volumes and transfusion requirements were recorded. RESULTS: Comparing the groups 2 h after bypass, the dextran group showed lower hemoglobin concentration, hematocrit, platelet count, and fibrinogen concentration, and higher INR and aPTT, as well as longer clot formation time (+41 ± 21 % vs. +8 ± 18 %, p < 0.001) and a larger reduction in fibrinogen-dependent clot strength (-37 ± 12 % vs. -7 ± 20 %, p < 0.001). Adenosine diphosphate-dependent platelet activation was reduced in the dextran group but not in the crystalloid group 2 h after bypass (-14 ± 29 % vs. -1 ± 41 %, p = 0.041). No significant between-group differences in hemostatic variables remained after 24 h, and no significant differences in perioperative bleeding volumes, re-explorations for bleeding, or transfusion rates were observed. CONCLUSIONS: Compared to a crystalloid solution, a dextran-based prime had measurable negative impact on hemostatic variables but no detectable increase in bleeding volume or transfusion requirements in cardiac surgery patients.

4H-SiC Schottky Barrier Diodes for Efficient Thermal Neutron Detection.

In this work, we present the improved efficiency of 4H-SiC Schottky barrier diodes-based detectors equipped with the thermal neutron converters. This is achieved by optimizing the thermal neutron converter thicknesses. Simulations of the optimal thickness of thermal neutron converters have been performed using two Monte Carlo codes (Monte Carlo N-Particle Transport Code and Stopping and Range of Ions in Matter). We have used 6LiF and 10B4C for the thermal neutron converter material. We have achieved the thermal neutron efficiency of 4.67% and 2.24% with 6LiF and 10B4C thermal neutron converters, respectively.

Sterilization of polypropylene membranes of facepiece respirators by ionizing radiation.

Ionizing radiation has been identified as an option for sterilization of disposable filtering facepiece respirators in situations where the production of the respirators cannot keep up with demand. Gamma radiation and high energy electrons penetrate deeply into the material and can be used to sterilize large batches of masks within a short time period. In relation to reports that sterilization by ionizing radiation reduces filtration efficiency of polypropylene membrane filters on account of static charge loss, we have demonstrated that both gamma and electron beam irradiation can be used for sterilization, provided that the respirators are recharged afterwards.

Testing of various neutron filters in reference neutron field in LR-0 reactor for nuclear data validation and verification.

Neutron activation analysis is the reference method used for offline determination of the neutron flux density in defined positions. It can be used in the nuclear energy industry-as well as in medical- or space applications. For accurate neutron flux evaluation, well-known and reliable cross sections are needed. In the thermal and fast energy region, many reliable monitoring reactions exists, however, in case of the epithermal and intermediate energy region, there are practically no dosimetry nuclear reactions sensitive specifically in this energy range. Due to this fact, both new data are being measured and methodologies are under development to describe and test this energy region. It was found that various neutron filters can be used to cut parts of neutron spectra and thus methodology based on spectrum filtering could potentially be employed to survey cross sections of interest. It this paper, the use of 3 different filters - B4C, Cd, and In is studied, on the case of the 55Mn(n,γ) reaction. Measured values of that cross section in the given filtered reference spectra are reported.

The Effect of Ex Vivo Factor XIII Supplementation on Clot Formation in Blood Samples From Cardiac and Scoliosis Surgery Patients.

Excessive perioperative bleeding remains a substantial problem. Factor XIII (FXIII) contributes to clot stability, and it has therefore been suggested that supplementation with FXIII concentrate may improve perioperative hemostasis. We evaluated the effects of increasing doses of FXIII, alone or in combination with fibrinogen or platelet concentrate, in blood samples from 2 considerably different groups of surgical patients: cardiac and scoliosis surgery patients. Whole-blood samples were collected immediately after operation from cardiac and scoliosis surgery patients. The samples were supplemented with 3 clinically relevant doses of FXIII concentrate (+20%, +40%, and +60%), alone or in combination with a fixed dose of fibrinogen concentrate (+1.0 g/L) or fresh apheresis platelets (+92 × 109/L). Clot formation was assessed with rotational thromboelastometry (ROTEM). When the highest dose of FXIII concentrate was added, EXTEM clotting time was shortened by 10% in both cardiac and scoliosis surgery patients (95% confidence intervals: 2.4%-17% and 3.3%-17%, respectively), and FIBTEM maximum clot firmness was increased by 25% (9.3%-41%) in cardiac patients, relative to baseline. When fibrinogen was added, the dose-dependent effect of FXIII on clot stability was maintained, but the total effect was markedly greater than with FXIII alone, +150% (100%-200%) and +160% (130%-200%) for the highest FXIII dose in cardiac and scoliosis patients, respectively. Ex vivo supplementation with clinically relevant doses of FXIII improved clot formation moderately in blood samples from cardiac and scoliosis surgery patients, both alone and when given in combination with fibrinogen or platelet concentrate.

Heparin and Protamine Titration Does Not Improve Haemostasis after Cardiac Surgery: A Prospective Randomized Study.

BACKGROUND: Bleeding complications are common in cardiac surgery. Perioperative handling of heparin and protamine may influence the haemostasis. We hypothesized that heparin and protamine dosing based on individual titration curves would improve haemostasis in comparison to standard dosing. SUBJECTS AND METHODS: Sixty patients scheduled for first time elective coronary artery bypass grafting or valve surgery were included in a prospective randomized study. The patients were randomized to heparin and protamine dosing with Hepcon HMS Plus device or to standard weight and activated clotting time (ACT) based dosing. Blood samples were collected before and 10 minutes, 2 hours and 4 hours after cardiopulmonary bypass. Primary endpoint was endogenous thrombin potential in plasma 2 hours after surgery as assessed by calibrated automated thrombography. Secondary endpoints included total heparin and protamine doses, whole blood clot formation (thromboelastometry) and post-operative bleeding volume and transfusions. Heparin effect was assessed by measuring anti-Xa activity. RESULTS: Endogenous thrombin potential and clot formation deteriorated in both groups after surgery without statistically significant intergroup difference. There were no significant differences between the groups in total heparin and protamine doses, heparin effect, or postoperative bleeding and transfusions at any time point. Significant inverse correlations between anti-Xa activity and endogenous thrombin potential were observed 10 min (r = -0.43, p = 0.001), 2 hours (r = -0.66, p<0.001) and 4 hours after surgery (r = -0.58, p<0.001). CONCLUSION: In conclusion, the results suggest that perioperative heparin and protamine dosing based on individual titration curves does not improve haemostasis after cardiac surgery. Postoperative thrombin generation capacity correlates to residual heparin effect. TRIAL REGISTRATION: www.isrctn.com ISRCTN14201041.

Validation of the neutron and gamma fields in the JSI TRIGA reactor using in-core fission and ionization chambers.

CEA developed fission chambers and ionization chambers were utilized at the JSI TRIGA reactor to measure neutron and gamma fields. The measured axial fission rate distributions in the reactor core are generally in good agreement with the calculated values using the Monte Carlo model of the reactor thus verifying both the computational model and the fission chambers. In future, multiple absolutely calibrated fission chambers could be used for more accurate online reactor thermal power monitoring.

Validation of absolute axial neutron flux distribution calculations with MCNP with 197Au(n,γ)198Au reaction rate distribution measurements at the JSI TRIGA Mark II reactor.

The calculation of axial neutron flux distributions with the MCNP code at the JSI TRIGA Mark II reactor has been validated with experimental measurements of the (197)Au(n,γ)(198)Au reaction rate. The calculated absolute reaction rate values, scaled according to the reactor power and corrected for the flux redistribution effect, are in good agreement with the experimental results. The effect of different cross-section libraries on the calculations has been investigated and shown to be minor.

Retransfusion of cardiotomy suction blood impairs haemostasis: ex vivo and in vivo studies.

OBJECTIVES: Cardiotomy suction blood in volumes corresponding to 10-20% of the systemic blood volume is retransfused during cardiopulmonary bypass. We hypothesized that retransfusion of unwashed cardiotomy suction blood influences coagulation and platelet function. DESIGN: Systemic blood samples collected during cardiopulmonary bypass were supplemented ex vivo with autologous wound blood (5, 10 and 20%, respectively). Clot formation and platelet function were assessed with thromboelastometry and platelet aggregometry. In an in vivo pilot study 30 patients were randomized into a retransfusion and a no-retransfusion group. Clot formation, platelet aggregability and thrombin generation capacity were compared between the groups. RESULTS: Cardiotomy suction blood had markedly impaired clot stability and reduced levels of fibrinogen and platelets compared with systemic blood. Ex vivo addition of 10% and 20% suction blood to systemic blood impaired platelet aggregability and clot stability. Retransfusion of small amounts of wound blood in vivo (mean volume 280 ml, corresponding to 5% of the blood volume) did not significantly influence haemostasis. CONCLUSIONS: The ex vivo results suggest that addition of unwashed cardiotomy suction blood in clinically relevant volumes impairs systemic haemostasis. Retransfusion of smaller volumes in vivo has no or limited impact. Avoiding retransfusion of larger amounts of unwashed cardiotomy suction may improve postoperative haemostasis.

Sustained heparin effect contributes to reduced plasma thrombin generation capacity early after cardiac surgery.

INTRODUCTION: Thrombin is a key component in the coagulation cascade, and impaired thrombin generation has been linked to increased bleeding after surgical procedures. The aim was to evaluate postoperative thrombin generation capacity in plasma after cardiac surgery, and its potential associations to activity of individual coagulation factors and heparin. MATERIAL AND METHODS: Forty-eight coronary artery bypass grafting patients were included in a prospective observational cohort study. Thrombin generation capacity was analysed in plasma with calibrated automated thrombogram with tissue factor as activator before (baseline), and 2 h and 24 h after surgery. In addition, plasma activity of coagulation factors II, V, VII, VIII, IX, X, XI, XIII, were determined. Heparin effect was assessed by anti-Xa activity, APTT and thrombin time. RESULTS: Thrombin generation was markedly reduced 2h after surgery compared to baseline. Peak levels decreased with median 74% (interquartile range 52-90), p<0.001, and endogenous thrombin generation potential decreased with 65% (43-86), p<0.001. Postoperative changes in endogenous thrombin generation potential correlated inversely to changes in anti-Xa activity (r=-0.51, p=0.010) and to changes in thrombin time (r=-0.51, p=0.009), but there were no correlations to changes in individual coagulation factor activity. CONCLUSIONS: A marked reduction in thrombin generation potential was observed in the early postoperative phase after cardiac surgery. The decrease was independent of reductions in individual coagulation factor activity but correlated to heparin effects. The results indicate that a sustained heparin effect contributes to the postoperative reduction in thrombin generation capacity.

Plasma activity of individual coagulation factors, hemodilution and blood loss after cardiac surgery: a prospective observational study.

BACKGROUND: Hemodilution and consumption of coagulation factors during cardiopulmonary bypass has been suggested to contribute to bleeding complications after cardiac surgery. The aim was to describe the activity of individual coagulation factors after CABG in relation to hemodilution and postoperative bleeding. MATERIALS AND METHODS: Plasma concentrations of fibrinogen and plasma activity of FII, FV, FVII, FVIII, FIX, FX, FXI and FXIII adjusted for hemodilution were analysed in 57 CABG patients before, and 2h and 24h after surgery. Postoperative bleeding was registered and correlations to coagulation factor activity were calculated. RESULTS: Adjusted plasma concentration of fibrinogen (-14+/-6%), and plasma activity of FII (-9+/-6%), FV (-13+/-8%), FX (-13+/-7%) and FXIII (-9+/-14%) were reduced two hours after surgery compared to baseline (all p<0.001). FVII (+3+/-12%, p=0.34) and FXI (+1+/-19%, p=0.50) were unchanged, while FVIII (+23+/-44%, p=0.006) and FIX (+23+/-17%, p<0.001) increased. Twenty-four hours after surgery fibrinogen (+45+/-27%), FVIII (+93+/-66%) and FIX (+33+/-26%) were all increased (all p<0.001), while FVII (-37+/-14%, p<0.001), FXI (-4+/-18%, p=0.02) and FXIII (-6+/-15%, p=0.004) were decreased. Median postoperative blood loss was 380 ml/12h. There were significant inverse correlations between postoperative blood loss and fibrinogen concentration 2h after surgery (r=-0.33, p=0.019) and between postoperative blood loss and pre- and postoperative FXIII activity (r=-0.34, p=0.009 and r=-0.41, p=0.003, respectively), but not between blood loss and any of the other factors. CONCLUSIONS: There is a marked dissociation in plasma activity of individual coagulation factors after CABG. Plasma concentration of fibrinogen and factor XIII activity correlates inversely to postoperative blood loss after CABG.

A brief update of glucocorticoid receptor variants and obesity risk.

Excess body fat, obesity, is one of the most common disorders in clinical practice. Obese individuals are at increased risk for physical ailments, such as type 2 diabetes, coronary heart disease, hypertension, and several types of cancer. The location of the body fat is a major determinant of the degree of excess morbidity and mortality due to obesity. More specifically, the amount of subcutaneous truncal or abdominal fat, and the amount of visceral fat located in the abdominal cavity independently predicts obesity-related adverse health outcomes. The obesity gene map shows putative loci on all chromosomes except Y. More than 300 genes, markers, and chromosomal regions have been associated or linked with human obesity phenotypes. These genes can be divided into two broad categories: (a) rare gene variants that have a strong influence, and (b) common gene variants that have a weaker influence on obesity phenotypes. Studies in humans have suggested a positive association between obesity, hypertension, and insulin resistance, with alleles at the glucocorticoid receptor gene. In this article, we will estimate the risk by which such gene polymorphism mediates a role in obesity.