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

Lawrence, Matthew; Kumar, Sanjeev; Hawkins, Karl; Boden, Stuart A.; Rutt, H.N.; Mills, Gavin; Sabra, Ahmed; Morris, Roger H. K.; Davidson, Simon; Badiei, Nafieseh; Brown, M. Rowan; Williams, P. R.; Evans, P A

doi:10.1016/j.thromres.2014.05.039

Cited by 28 publications

(37 citation statements)

References 33 publications

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“…using data from a previous study where the df at 0% dilution was 1.73±0.035, and expecting a decrease in df of around 0.06 as dilution is increased. 12 Assuming an  of 0.05 and a power of 0.90, we calculated that 8 subjects would be required for each studied dilution, with a total of 4 different dilutions and 3 different fluids (with an additional 8 for a 0% dilution) giving a total of 104 participants.…”

Section: Discussionmentioning

confidence: 99%

An Investigation Into the Effects of In Vitro Dilution With Different Colloid Resuscitation Fluids on Clot Microstructure Formation

Lawrence

Marsden

Kaczynski

et al. 2016

Anesthesia &Amp; Analgesia

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Section: Discussionmentioning

confidence: 99%

An Investigation Into the Effects of In Vitro Dilution With Different Colloid Resuscitation Fluids on Clot Microstructure Formation

Lawrence

Marsden

Kaczynski

et al. 2016

Anesthesia &Amp; Analgesia

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“…9 The GP technique has been previously validated for use with blood in several studies. [10][11][12][13][14][15] Briefly, blood is placed within the double concentric measuring geometry of a controlled stress rheometer, AR-G2 (TA Instruments, New Castle, DE, USA) which is held a constant temperature of 37°C±0.1°C (figure 1). Immediately after loading the blood into the AR-G2, viscoelastic analysis is preformed using small amplitude oscillatory shear measurements at varying frequencies; 2, 0.93, 0.43 and 0.2 Hz, with an applied peak stress amplitude of 0.03 Pa.…”

Section: Viscoelastic Measurementsmentioning

confidence: 99%

Characterisation of clot microstructure properties in stable coronary artery disease

et al. 2017

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BackgroundCoronary artery disease (CAD) is associated with an increased prothrombotic tendency and is also linked to unfavourably altered clot microstructure. We have previously described a biomarker of clot microstructure (df) that is unfavourably altered in acute myocardial infarction. The df biomarker assesses whether the blood will form denser or looser microstructures when it clots. In this study we assessed in patients with stable chest pain whether df can differentiate between obstructed and unobstructed CAD.MethodsA blood sample prior to angiography was obtained from 251 consecutive patients undergoing diagnostic coronary angiography. Patients were categorised based on angiographic findings as presence or absence of obstructive CAD (stenosis ≥50%). The blood sample was assessed using the df biomarker, standard laboratory markers and platelet aggregometry (Multiplate).ResultsA significant difference (p=0.028) in df was observed between obstructive CAD (1.748±0.057, n=83) and unobstructive CAD (1.732±0.052, n=168), where patients with significant CAD produce denser, more tightly packed clots. df was also raised in men with obstructive CAD compared with women (1.745±0.055 vs 1.723±0.052, p=0.007). Additionally df significantly correlated with the platelets response to arachidonic acid as measured by the ASPItest area under the curve readings from platelet aggregometry (correlation coefficient=0.166, p=0.008), a low value of the ASPItest indicating effective aspirin use was associated with looser, less dense clots.ConclusionsFor the first time, we characterise clot microstructure, as measured by df, in patients with stable CAD. df can potentially be used to risk-stratify patients with stable CAD and assess the efficacy of therapeutic interventions by measuring changes in clot microstructure.

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“…We have previously demonstrated that a new biomarker, fractal dimension (d f ), capable of quantifying changes to the inter-dependent variables of haemostasis, clot microstructure and clot development in a more sensitive manner than conventional markers of clot initiation and propagation in healthy individuals [19]. In addition, d f has also been shown to quantify altered physiological effects and the relationship between kinetic changes and clot formation in patients with known vascular inflammatory disease in hypo and hypercoagulable states [19][20][21][22][23] haemodilution [24] and in response to different temperatures [25].…”

Section: Standard Kinetic Markers Of Initiation Propagation and Amplmentioning

confidence: 99%

Effects of exercise intensity on clot microstructure and mechanical properties in healthy individuals

Davies

Llwyd

Brugniaux

et al. 2016

Thrombosis Research

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BackgroundExercise is well established to lead to exercise-induced hypercoagulability, as demonstrated by kinetic coagulation markers. It remains unclear as to whether exercise-induces changes lead in clot development and increased polymerisation. Fractal dimension (df) has been shown to act as a marker of clot microstructure and mechanical properties, and may provide a more meaningful method of determining the relationship between exercise-induced hypercoagulability and potential clot development.Methods df was measured in 24 healthy individuals prior to, after 5 min of submaximal exercise, following maximal exercise, 45 min of passive recovery and following 60 min of recovery. Results were compared with conventional markers of coagulation, fibrinolysis and SEM images. ResultsSignificantly increased df was observed following exercise, returning to resting values following 60 min of recovery. The relationship between df and mature clot microstructure was confirmed by SEM: higher df was associated with dense clots formed of smaller fibrin fibres immediately following exercise compared to at rest. Conventional markers of coagulation confirmed findings of previous studies. ConclusionThis study demonstrates that df is a sensitive technique which quantifies the structure and properties of blood clots following exercise. In healthy individuals, the haemostatic balance between coagulation and fibrinolysis is maintained in equilibrium following exercise. In individuals with underlying vascular damage who participate in exercise, this equilibrium may be displaced and lead to enhanced clot formation and a prothrombotic state. df may therefore have the potential to not only quantify hypercoagulability, but may also be useful in screening these individuals.

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

Abstract: (244)Introduction: We investigated the effect of progressive haemodilution on the dynamics of fibrin

Cited by 28 publications

References 33 publications

An Investigation Into the Effects of In Vitro Dilution With Different Colloid Resuscitation Fluids on Clot Microstructure Formation

An Investigation Into the Effects of In Vitro Dilution With Different Colloid Resuscitation Fluids on Clot Microstructure Formation

Characterisation of clot microstructure properties in stable coronary artery disease

Effects of exercise intensity on clot microstructure and mechanical properties in healthy individuals

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