The effect of sepsis and its inflammatory response on mechanical clot characteristics: a prospective observational study

Davies, Gareth; Pillai, Suresh; Lawrence, Matthew; Mills, Gavin; Aubrey, Robert; D’Silva, Lindsay; Battle, Ceri; Williams, R. L.; Brown, M. Rowan; Thomas, Dafydd; Morris, Keith; Evans, P A

doi:10.1007/s00134-016-4496-z

Cited by 12 publications

(16 citation statements)

References 33 publications

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“…These findings provide more evidence that a clear hypercoagulable state is associated with sepsis, with increased clot mass and viscoelasticity (MCF), as has been shown in previous studies [1,18,19]. thromboelastometry.…”

Section: Discussionsupporting

confidence: 83%

“…thromboelastometry. This is indicative of a normally formed clot in septic shock, despite there being significant alterations in clotting time and fibrinolysis and is in contrast to recent studies which have specifically measured new markers of clot elasticity and strength [19]. These studies have shown that clot strength was significantly weakened when going from severe sepsis to the septic shock phase which was thought to be due to the effect on the mechanical strength by alteration of the cross-linked fabric leading to a looser, weaker clot.…”

Section: Discussioncontrasting

confidence: 58%

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The effect of sepsis and septic shock on the viscoelastic properties of clot quality and mass using rotational thromboelastometry: A prospective observational study

Davies

Lawrence

Pillai

et al. 2018

Journal of Critical Care

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Section: Discussionsupporting

confidence: 83%

Section: Discussioncontrasting

confidence: 58%

The effect of sepsis and septic shock on the viscoelastic properties of clot quality and mass using rotational thromboelastometry: A prospective observational study

Davies

Lawrence

Pillai

et al. 2018

Journal of Critical Care

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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%

“…9 The d f measurement has been previously validated in several disease states and has also been used to stratify the severity of disease, however, its role in stable CAD remains unclear. [10][11][12][13][14] The aim of the present study was to characterise clot microstructure in CAD. The hypothesis was that for a cohort of patients with suspected CAD undergoing diagnostic angiography, d f will be unfavourably altered in those patients with obstructive CAD compared with those with no or unobstructive CAD.…”

Section: Introductionmentioning

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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“…Recent rheological studies have highlighted the ability to scientifically and accurately quantify the quality and arrangement of clot microstructure that occur during clot development by measuring its fractal dimension (Df) [10]. Df has demonstrated a significant effect of changes in temperature and fluid dilution on clot microstructure [11][12][13] and more recently in clinical studies, to detect abnormal clot microstructure in response to the inflammatory changes seen in cancer, stroke and sepsis patients, even when standard laboratory tests have not [14][15][16]. The effect of burn injury on clot microstructure and clot quality has not previously been quantified.…”

Section: Introductionmentioning

confidence: 99%

The effect of the acute inflammatory response of burns and its treatment on clot characteristics and quality: A prospective case controlled study

Marsden

Lawrence

Davies

et al. 2020

Burns

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Burns are known to have an effect on coagulation in the early post burn period. Current coagulation tests have been criticised in acute burns due to their inherent limitations. This study aims to investigate the potential for a new quantitative functional biomarker of clot quality, fractal dimension, to identify changes in clot microstructure as a result of the burn inflammatory response and its treatment. Methods: A total of fifty-eight burn patients were included in this prospective case-controlled study. The control group (29 patients mean TBSA 1%), and case group (29 patients mean TBSA 30%) were compared at baseline and the case group investigated further over four time points (baseline, 12 hours, 24 hours and 5-7 days). Fractal analysis was performed, as well as current markers of coagulation, inflammatory markers and point-of-care tests, Thromboelastography and Multiplate analysis. Results: Fractal dimension did not differ between groups at admission (1.73 ± 0.06 and 1.72 ± 0.1), and fell within the healthy index normal range (1.74 ± 0.7), suggesting a normal clot microstructure in the early post burn period. Fractal dimension significantly reduced from baseline over the first 24 hours post burn (1.59 ± 0.03 p <0.005), indicating a significant reduction in mechanical clot strength and functionality consistent with a hypocoagulable state, not identified with other markers. Conclusions: This is the first study to quantify the changes in clot microstructure following burn injury. This study confirms clot microstructure is significantly altered during the first 24 hours post burn, with the production of a weaker, more porous fibrin clot, consistent with a hypocoagulable state.

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The effect of sepsis and its inflammatory response on mechanical clot characteristics: a prospective observational study

Abstract: This study confirms that clot microstructure is significantly altered through the various stages of sepsis. Of particular importance was the marked change in clot development between severe sepsis and septic shock, which has not been previously reported.

Cited by 12 publications

References 33 publications

The effect of sepsis and septic shock on the viscoelastic properties of clot quality and mass using rotational thromboelastometry: A prospective observational study

The effect of sepsis and septic shock on the viscoelastic properties of clot quality and mass using rotational thromboelastometry: A prospective observational study

Characterisation of clot microstructure properties in stable coronary artery disease

The effect of the acute inflammatory response of burns and its treatment on clot characteristics and quality: A prospective case controlled study

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