i-Rheo: Measuring the materials' linear viscoelastic properties “in a step”!

A new analytical technique for determining a materials' linear viscoelastic properties from a simple step-strain measurement is reported. The technique avoids the need for idealisation of real measurements. The technique involves evaluating the Fourier transforms of raw experimental data describing both the time-dependent stress and strain functions. A comparison with conventional linear oscillatory measurements for a diverse range of complex materials is made and the technique is shown to be superior to existing linear oscillatory measurements in all cases

The Role of Whole Blood Impedance Aggregometry and Its Utilisation in the Diagnosis and Prognosis of Patients with Systemic Inflammatory Response Syndrome and Sepsis in Acute Critical Illness

Objective: To assess the prognostic and diagnostic value of whole blood impedance aggregometry in patients with sepsis and SIRS and to compare with whole blood parameters (platelet count, haemoglobin, haematocrit and white cell count). Methods: We performed an observational, prospective study in the acute setting. Platelet function was determined using whole blood impedance aggregometry (multiplate) on admission to the Emergency Department or Intensive Care Unit and at 6 and 24 hours post admission. Platelet count, haemoglobin, haematocrit and white cell count were also determined. Results: 106 adult patients that met SIRS and sepsis criteria were included. Platelet aggregation was significantly reduced in patients with severe sepsis/septic shock when compared to SIRS/uncomplicated sepsis (ADP: 90.7±37.6 vs 61.4±40.6; p<0.001, Arachadonic Acid 99.9±48.3 vs 66.3±50.2; p = 0.001, Collagen 102.6±33.0 vs 79.1±38.8; p = 0.001; SD ± mean)). Furthermore platelet aggregation was significantly reduced in the 28 day mortality group when compared with the survival group (Arachadonic Acid 58.8±47.7 vs 91.1±50.9; p<0.05, Collagen 36.6±36.6 vs 98.0±35.1; p = 0.001; SD ± mean)). However haemoglobin, haematocrit and platelet count were more effective at distinguishing between subgroups and were equally effective indicators of prognosis. Significant positive correlations were observed between whole blood impedance aggregometry and platelet count (ADP 0.588 p<0.0001, Arachadonic Acid 0.611 p<0.0001, Collagen 0.599 p<0.0001 (Pearson correlation)). Conclusions: Reduced platelet aggregometry responses were not only significantly associated with morbidity and mortality in sepsis and SIRS patients, but also correlated with the different pathological groups. Whole blood aggregometry significantly correlated with platelet count, however, when we adjust for the different groups we investigated, the effect of platelet count appears to be non-significant

Platelet reactivity influences clot structure as assessed by fractal analysis of viscoelastic properties

<p>Despite the interwoven nature of platelet activation and the coagulation system in thrombosis, few studies relate both analysis of protein and cellular parts of coagulation in the same population. In the present study, we use matched ex vivo samples to determine the influences of standard antiplatelet therapies on platelet function and use advanced rheological analyses to assess clot formation. Healthy volunteers were recruited following fully informed consent then treated for 7 days with single antiplatelet therapy of aspirin (75 mg) or prasugrel (10 mg) or with dual antiplatelet therapy (DAPT) using aspirin (75 mg) plus prasugrel (10 mg) or aspirin (75 mg) plus ticagrelor (90 mg). Blood samples were taken at day 0 before treatment and at day 7 following treatment. We found that aspirin plus prasugrel or aspirin plus ticagrelor inhibited platelet responses to multiple agonists and reduced P-selectin expression. Significant platelet inhibition was coupled with a reduction in fractal dimension corresponding to reductions in mean relative mass both for aspirin plus prasugrel (−35 ± 16% change, p = 0.04) and for aspirin plus ticagrelor (−45 ± 14% change, p = 0.04). Aspirin alone had no effect upon measures of clot structure, whereas prasugrel reduced fractal dimension and mean relative mass. These data demonstrate that platelets are important determinants of clot structure as assessed by fractal dimension (d_<i>f</i>) and that effective platelet inhibition is associated with a weaker, more permeable fibrin network. This indicates a strong association between the therapeutic benefits of antiplatelet therapies and their abilities to reduce thrombus density that may be useful in individual patients to determine the functional relationship between platelet reactivity, eventual clot quality, and clinical outcome. d_<i>f</i> could represent a novel risk stratification biomarker useful in individualizing antiplatelet therapies.</p

A new structural biomarker that quantifies and predicts changes in clot strength and quality in a model of progressive haemodilution

Introduction: We investigated the effect of progressive haemodilution on the dynamics of fibrin clot formation and clot microstructure using a novel rheological method. The technique measures clotting time (T_GP), clot strength (G'_GP), and quantifies clot microstructure (d_f) at the incipient stages of fibrin formation. We use computational modelling to examine the relationship between structure and mass, as well as helium ion microscopy (HIM) to compare morphological changes in the fully formed clot to that of the incipient clot.Methods: This is an in vitro study; 90 healthy volunteers were recruited with informed consent and a 20 ml sample of whole blood obtained from each volunteer. Five clinically relevant dilutions were investigated using 0.9w.v isotonic saline (0, 10, 20, 40 and 60%, n = 18 for each dilution). The rheological method of assessing structural clot changes was compared against conventional coagulation screen and fibrinogen estimation.Results: Fractal dimension (df) and final clot microstructure both decreased with progressive dilution (significant at a dilution of 20%) with similar relationships observed for final clot characteristics in HIM images. Significant correlations were observed between d_f and G'_GP (clot strength) (0.345, p = 0.02), as well as clotting time (PT: -0.690, p &gt; 0.001; APTT: -0.672, p &gt; 0.001; T_GP: -0.385, p = 0.006).Conclusions: This study provides new insight into the effects of haemodilution by isotonic saline on clotting time (T_GP), clot strength (G'_GP) and clot microstructure (d_f). Previous studies have attempted to link clot microstructure to clot quality/strength, however this study provides a significant step in quantifying these relationships

Receiver operating characteristics for discrimination between SIRS/Uncomplicated Sepsis and Severe Sepsis/Septic Shock groups.

<p>Receiver operating characteristics are shown for platelet aggregometry measurements, whole blood parameters and sepsis-related organ failure assessment (SOFA) score as a discriminator between patients with and without organ dysfunction.</p

Receiver operating characteristics for discrimination between survivors and non-survivors at 28 days.

<p>Receiver operating characteristics are shown for platelet aggregometry measurements and whole blood parameters for the discrimination between 28-day mortality and survival.</p

Demographics of Subject Groups.

<p>COPD  =  Chronic Obstructive Pulmonary Disease; SOFA  =  Sepsis-relates Organ Failure Assessment; LOS  =  Length of Stay.</p><p>Demographics of Subject Groups.</p

Receiver Operating Characteristics for Survivors and Non-Survivors for Platelet Aggregation and Whole Blood Parameters.

<p>Receiver Operating Characteristics for Survivors and Non-Survivors for Platelet Aggregation and Whole Blood Parameters.</p

Pearson's Correlations of Whole Blood Aggregometry versus Whole Blood Parameters.

<p>Pearson's Correlations of Whole Blood Aggregometry versus Whole Blood Parameters.</p

Comparison of SIRS/Uncomplicated sepsis and severe sepsis/septic shock.

<p>Comparison of SIRS/Uncomplicated sepsis and severe sepsis/septic shock.</p