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

A new structural biomarker that quantifies and predicts changes in clot strength and quality in a model of progressive haemodilution
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 > 0.001; APTT: -0.672, p > 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.
0049-3848
488-494
Lawrence, Matthew J.
76aef46e-f0d8-4af4-8fa0-0bf4219d8956
Kumar, Sendhil
e5af7f8b-4957-47b3-86e9-ec3f551e9024
Hawkins, Karl
50b533e3-60ee-44e8-a53a-67ca2393c741
Boden, Stuart
83976b65-e90f-42d1-9a01-fe9cfc571bf8
Rutt, Harvey
e09fa327-0c01-467a-9898-4e7f0cd715fc
Mills, Gavin
c1b1d6c7-c462-4950-99bf-c20d1b7f057a
Sabra, Ahmed
4ecee77b-d608-47a3-8952-26cc0b9489e4
Morris, Roger H.K.
b09ce969-4850-4c8d-bed2-4b35e3196f6d
Davidson, Simon J.
8def5e51-867d-4aed-a29c-c54b00a099f4
Badiei, Nafieseh
320808ac-bff9-4950-a432-7947bba6ad47
Brown, Martin R.
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Williams, Phylip R.
879581c2-d40d-4f6e-99b3-b074dacfa170
Evans, Phillip A.
25a9d018-a793-4cf1-ab7e-39cd6464c117
Lawrence, Matthew J.
76aef46e-f0d8-4af4-8fa0-0bf4219d8956
Kumar, Sendhil
e5af7f8b-4957-47b3-86e9-ec3f551e9024
Hawkins, Karl
50b533e3-60ee-44e8-a53a-67ca2393c741
Boden, Stuart
83976b65-e90f-42d1-9a01-fe9cfc571bf8
Rutt, Harvey
e09fa327-0c01-467a-9898-4e7f0cd715fc
Mills, Gavin
c1b1d6c7-c462-4950-99bf-c20d1b7f057a
Sabra, Ahmed
4ecee77b-d608-47a3-8952-26cc0b9489e4
Morris, Roger H.K.
b09ce969-4850-4c8d-bed2-4b35e3196f6d
Davidson, Simon J.
8def5e51-867d-4aed-a29c-c54b00a099f4
Badiei, Nafieseh
320808ac-bff9-4950-a432-7947bba6ad47
Brown, Martin R.
f7c18d3f-d360-4221-9df2-31fad7cff3a0
Williams, Phylip R.
879581c2-d40d-4f6e-99b3-b074dacfa170
Evans, Phillip A.
25a9d018-a793-4cf1-ab7e-39cd6464c117

Lawrence, Matthew J., Kumar, Sendhil, Hawkins, Karl, Boden, Stuart, Rutt, Harvey, Mills, Gavin, Sabra, Ahmed, Morris, Roger H.K., Davidson, Simon J., Badiei, Nafieseh, Brown, Martin R., Williams, Phylip R. and Evans, Phillip A. (2014) A new structural biomarker that quantifies and predicts changes in clot strength and quality in a model of progressive haemodilution. Thrombosis Research, 134 (2), 488-494. (doi:10.1016/j.thromres.2014.05.039). (PMID:24965661)

Record type: Article

Abstract

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 > 0.001; APTT: -0.672, p > 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.

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Accepted/In Press date: 22 May 2014
e-pub ahead of print date: 6 June 2014
Published date: August 2014
Organisations: Electronics & Computer Science

Identifiers

Local EPrints ID: 367880
URI: https://eprints.soton.ac.uk/id/eprint/367880
ISSN: 0049-3848
PURE UUID: 7039cf4a-0f74-45c1-a74a-22c09b0113e1
ORCID for Stuart Boden: ORCID iD orcid.org/0000-0002-4232-1828

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Date deposited: 08 Aug 2014 13:41
Last modified: 29 Oct 2019 01:50

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Contributors

Author: Matthew J. Lawrence
Author: Sendhil Kumar
Author: Karl Hawkins
Author: Stuart Boden ORCID iD
Author: Harvey Rutt
Author: Gavin Mills
Author: Ahmed Sabra
Author: Roger H.K. Morris
Author: Simon J. Davidson
Author: Nafieseh Badiei
Author: Martin R. Brown
Author: Phylip R. Williams
Author: Phillip A. Evans

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