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Changes in platelet function with inflammation in patients undergoing vascular surgery

Changes in platelet function with inflammation in patients undergoing vascular surgery
Changes in platelet function with inflammation in patients undergoing vascular surgery
The role of platelets in ischaemic events is well established. Aspirin represents the default antiplatelet and blocks the metabolism of arachidonic acid (AA) at the cyclo-oxygenase enzyme (COX). AA is commonly used as a test of response to aspirin, but recent data raise uncertainty about the validity of this approach. Specifically, in some patients AA-induced clotting is not suppressed, but the level of COX-dependent AA metabolite, thromboxane B2 (TXB2) is negligible. Furthermore, AA-induced whole blood clotting varies dynamically in individuals, who are aspirin responsive according to TXB2 levels. The aim of this study was to assess the level of AA-, ADP- and thrombin-mediated platelet reactivity in patients on aspirin before, during, and after major vascular surgery, which represents a model of on/off vascular inflammation. Firstly, we hypothesised, that in association with this inflammatory episode AA-, ADP- and thrombin-induced clotting would change in a dynamic manner. Secondly, that AA-induced clotting will be modified despite complete suppression of platelet TXB2 production by aspirin throughout the periprocedural period, possibly via a lipoxygenase-mediated mechanism. Fourty patients underwent major vascular surgery (open abdominal aortic aneurysm operation, infrainguinal bypass for subcritical limb ischaemia or peripheral aneurysm repair with bypass). They were all on 75 mg of aspirin prior to and throughout the perioperative period and received 5000 units of unfractionated heparin intraoperatively. AA-, ADP- and thrombin- induced clotting, AA metabolites (TXB2 and 12-Hyroxyeicosatetraenoic acid (12- HETE)) and inflammatory markers (CRP, IL-6, TNF-α and CD40) were measured preprocedure and at 2, 24, 48 hours, 3 to 5 days and 3 months after surgery. AA-, ADP- and thrombin- induced platelet reactivity was assessed using thrombelastography. TxB2, 12- HETE, IL-6, TNF-α, CD40 were determined using the sequential competitive binding Enzyme-Linked ImmunoAssay technique and CRP was determined using an immune-turbidimetric test on human serum. There was a transient rise in inflammatory markers in the early perioperative period (CRP at 24, 48 hours and 3 to 5 days p<0.001 and IL-6 at 2, 24, 48 hours and 3 to 5 days p<0.001 as compared to baseline). Patients had negligible levels of TxB throughout, confirming a consistent therapeutic response to aspirin. There was a transient rise in thrombin-mediated clotting (MAThrombin at 48 hours p=0.001 and 3 to 5 days p<0.001) and a fall in AA- and ADP-induced clotting in the early post op period (both MAAA and MAADP p=0.001 at 2 hours). At 3 months, the level of AA- and ADP-induced clotting was significantly higher than at baseline (p=0.008 for MAAA and p=0.002 for MAADP), hence demonstrating a rebound effect.  These data demonstrate a novel dynamic variation in platelet aggregation with acute vascular inflammation, including AA-induced whole blood clotting which is apparently COX-1 independent.
0953-7104
190-198
Olechowski, Bartosz
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Khanna, Vikram
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Mariathas, Mark
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Ashby, Alexander
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Dalton, Richard T.
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Nordon, Ian
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Englyst, Nicola
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Harris, Scott
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Nicholas, Zoe
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Thayalasamy, Kala
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Mahmoudi, Michael
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Curzen, Nicholas
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Olechowski, Bartosz
b025b40b-f9fa-4b8e-8f57-310d47e57700
Khanna, Vikram
17b557ad-b071-4d1a-84dd-3ba58470cee0
Mariathas, Mark
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Ashby, Alexander
f403fd28-7991-4d70-96c5-9dccdf339e32
Dalton, Richard T.
22502b2a-837e-44b0-ab88-17804a1cb995
Nordon, Ian
6745d713-4f2d-4fdd-ab99-0c95bb053e91
Englyst, Nicola
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Harris, Scott
19ea097b-df15-4f0f-be19-8ac42c190028
Nicholas, Zoe
98403583-c418-45ad-836b-1831517dcc5f
Thayalasamy, Kala
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Mahmoudi, Michael
f6a55246-399e-4f81-944e-a4b169786e8a
Curzen, Nicholas
70f3ea49-51b1-418f-8e56-8210aef1abf4

Olechowski, Bartosz, Khanna, Vikram, Mariathas, Mark, Ashby, Alexander, Dalton, Richard T., Nordon, Ian, Englyst, Nicola, Harris, Scott, Nicholas, Zoe, Thayalasamy, Kala, Mahmoudi, Michael and Curzen, Nicholas (2019) Changes in platelet function with inflammation in patients undergoing vascular surgery. Platelets, 30 (2), 190-198. (doi:10.1080/09537104.2017.1392498).

Record type: Article

Abstract

The role of platelets in ischaemic events is well established. Aspirin represents the default antiplatelet and blocks the metabolism of arachidonic acid (AA) at the cyclo-oxygenase enzyme (COX). AA is commonly used as a test of response to aspirin, but recent data raise uncertainty about the validity of this approach. Specifically, in some patients AA-induced clotting is not suppressed, but the level of COX-dependent AA metabolite, thromboxane B2 (TXB2) is negligible. Furthermore, AA-induced whole blood clotting varies dynamically in individuals, who are aspirin responsive according to TXB2 levels. The aim of this study was to assess the level of AA-, ADP- and thrombin-mediated platelet reactivity in patients on aspirin before, during, and after major vascular surgery, which represents a model of on/off vascular inflammation. Firstly, we hypothesised, that in association with this inflammatory episode AA-, ADP- and thrombin-induced clotting would change in a dynamic manner. Secondly, that AA-induced clotting will be modified despite complete suppression of platelet TXB2 production by aspirin throughout the periprocedural period, possibly via a lipoxygenase-mediated mechanism. Fourty patients underwent major vascular surgery (open abdominal aortic aneurysm operation, infrainguinal bypass for subcritical limb ischaemia or peripheral aneurysm repair with bypass). They were all on 75 mg of aspirin prior to and throughout the perioperative period and received 5000 units of unfractionated heparin intraoperatively. AA-, ADP- and thrombin- induced clotting, AA metabolites (TXB2 and 12-Hyroxyeicosatetraenoic acid (12- HETE)) and inflammatory markers (CRP, IL-6, TNF-α and CD40) were measured preprocedure and at 2, 24, 48 hours, 3 to 5 days and 3 months after surgery. AA-, ADP- and thrombin- induced platelet reactivity was assessed using thrombelastography. TxB2, 12- HETE, IL-6, TNF-α, CD40 were determined using the sequential competitive binding Enzyme-Linked ImmunoAssay technique and CRP was determined using an immune-turbidimetric test on human serum. There was a transient rise in inflammatory markers in the early perioperative period (CRP at 24, 48 hours and 3 to 5 days p<0.001 and IL-6 at 2, 24, 48 hours and 3 to 5 days p<0.001 as compared to baseline). Patients had negligible levels of TxB throughout, confirming a consistent therapeutic response to aspirin. There was a transient rise in thrombin-mediated clotting (MAThrombin at 48 hours p=0.001 and 3 to 5 days p<0.001) and a fall in AA- and ADP-induced clotting in the early post op period (both MAAA and MAADP p=0.001 at 2 hours). At 3 months, the level of AA- and ADP-induced clotting was significantly higher than at baseline (p=0.008 for MAAA and p=0.002 for MAADP), hence demonstrating a rebound effect.  These data demonstrate a novel dynamic variation in platelet aggregation with acute vascular inflammation, including AA-induced whole blood clotting which is apparently COX-1 independent.

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Changes in platelet function with inflammation Submitted 05 10 17 - Accepted Manuscript
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Accepted/In Press date: 5 October 2017
e-pub ahead of print date: 11 December 2017
Published date: 2019

Identifiers

Local EPrints ID: 416144
URI: http://eprints.soton.ac.uk/id/eprint/416144
ISSN: 0953-7104
PURE UUID: 2f0beb75-07b2-4fe0-a297-447fda4e48bb
ORCID for Nicola Englyst: ORCID iD orcid.org/0000-0003-0508-8323
ORCID for Michael Mahmoudi: ORCID iD orcid.org/0000-0003-1293-8461
ORCID for Nicholas Curzen: ORCID iD orcid.org/0000-0001-9651-7829

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Date deposited: 06 Dec 2017 17:30
Last modified: 22 Nov 2021 05:57

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Contributors

Author: Bartosz Olechowski
Author: Vikram Khanna
Author: Mark Mariathas
Author: Alexander Ashby
Author: Richard T. Dalton
Author: Ian Nordon
Author: Nicola Englyst ORCID iD
Author: Scott Harris
Author: Zoe Nicholas
Author: Kala Thayalasamy
Author: Nicholas Curzen ORCID iD

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