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IntroductionCoagulation pathway changes play an important role in the outcome of both clot propagation and fibrinolysis. The structurefunction relationship of the developing fibrin clot is known to be affected by many factors, such as environment, therapy, and disease, compared with normal clot growth. 1,2 A fibrin clot's primary microstructure consists of a disordered network of entangled, branching fibrin fibers. Thinner fibers are associated with networks that display an increased number of branch points, creating denser, less permeable clots that have a known association with thromboembolic disease. [3][4][5][6] More open/permeable networks are formed from thicker fibers, the latter displaying a reduced number of branch points for a given amount of fibrinogen and producing a more porous system. [7][8][9][10] Clots with altered fibrin microstructure exhibit different susceptibility to fibrinolysis, 8,10,11 with clot permeability being the rate-limiting factor for the activity of the fibrin network degradation enzyme plasmin. The permeability will aid or hamper the ability of tissue plasmin activator, tPA, and/or urokinase plasmin activator to move through the 3-dimensional fibrin network and activate the zymogen plasminogen to fibrinolytic plasmin. The effect of anticoagulants such as heparin in the therapeutic manipulation of fibrin clot microstructure by thrombin inhibition increases clot permeability/porosity and produces clots with thicker fibers. 12,13 The evolution of clot microstructure is associated with significant changes in blood viscoelasticity (a measure of a material's viscous and elastic properties). Viscoelastic properties are among the most sensitive measures of fibrin polymerization and blood clot structure. 7,14 In the present study, we focused on the formation of the incipient clot, which provides the microstructural template that determines the future clot morphology, 15-17 by measuring the incipient clot's viscoelastic properties with an oscillatory shear technique known as Fourier transform mechanical spectroscopy (FTMS). [18][19][20] This technique provides an accurate determination of the gel point (GP) of coagulating blood and allows the microstructure of the incipient clot to be quantified by fractal analysis, a technique widely used in medicine and biology to characterize nonlinear growth in branching network structures. 21 The authors of previous studies of clot structure on the basis of techniques such as scanning electron microscopy have reported qualitative descriptions of clot microstructure (involving terms such as "rigid clot structures," "open/porous/dense/loose," etc 1 ), whereas studies of the fractal properties of fibrin gels on the basis of light-scattering techniques have been restricted to dilute solutions of fibrinogen, at concentrations less than those of physiologic relevance in whole blood. 22 A recent study of fibrin clot structure suggests there is a definitive diagnostic potential of characterizing clot structure and the modulation of clot architecture as a pos...

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BackgroundStroke is the second largest cause of death worldwide. Hypercoagulability is a key feature in ischaemic stroke due to the development of an abnormally dense clot structure but techniques assessing the mechanics and quality of clot microstructure have limited clinical use. We have previously validated a new haemorheological technique using three parameters to reflect clot microstructure (Fractal Dimension (df)) ex-vivo, real-time clot formation time (TGP) and blood clot strength (elasticity at the gel point (G’GP)). We aimed to evaluate these novel clotting biomarkers in ischaemic stroke and changes of clot structure following therapeutic intervention.MethodsIn a prospective cohort study clot microstructure was compared in ischaemic stroke patients and a control group of healthy volunteers. Further assessment took place at 2–4 hours and at 24 hours after therapeutic intervention in the stroke group to assess the effects of thrombolysis and anti-platelet therapy.Results75 patients (mean age 72.8 years [SD 13.1]; 47 male, 28 female) with ischaemic stroke were recruited. Of the 75 patients, 32 were thrombolysed with t-PA and 43 were loaded with 300 mg aspirin. The following parameters were significantly different between patients with stroke and the 74 healthy subjects: df (1.760 ± .053 versus 1.735 ± 0.048, p = 0.003), TGP (208 ± 67 versus 231 ± 75, p = 0.05), G’GP (0.056 ± 0.017 versus 0.045 ± 0.014, p < 0.0001) and fibrinogen (3.7 ± 0.8 versus 3.2 ± 0.5, p < 0.00001). There was a significant decrease in df (p = 0.02), G’GP (p = 0.01) and fibrinogen (p = 0.01) following the administration of aspirin and for df (p = 0.003) and fibrinogen (p < 0.001) following thrombolysis as compared to baseline values.ConclusionPatients with ischaemic stroke have denser and stronger clot structure as detected by df and G’GP. The effect of thrombolysis on clot microstructure (df) was more prominent than antiplatelet therapy. Further work is needed to assess the clinical and therapeutic implications of these novel biomarkers.

Abstract:We describe experimental results on the extensional viscosity of mobile polymer solutions obtained from two instruments, the first being a commercial Spin Line Rheometer and the second a custom-built lubricated-die Converging Flow Rheometer. The interpretation of data in terms of Trouton ratios is facilitated by a simple analysis for the Generalized Newtonian Fluid model. Agreement between data from the two rheometers is satisfactory and we show that polymer solutions can be either tension stiffening or tension thinning. However, the Trouton ratios in both cases are greater than the Newtonian values and we anticipate that this will always be the case for polymer solutions.