Comparison of nine platelet function tests used to determine responses to different aspirin dosages in people with type 2 diabetes

The antiplatelet efficacy of aspirin (ASA) is reduced in type 2 diabetes (T2D). As the best ex vivo method of measuring ASA efficacy remains uncertain, we compared nine platelet function tests to assess responsiveness to three ASA dosing regimens in 24 T2D patients randomized in a three-treatment cr...

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Main Authors: Paul Harrison, M. Angelyn Bethel, Irene Kennedy, Robert Dinsdale, Ruth Coleman, Rury R. Holman
Format: Article
Language:English
Published: Taylor & Francis Group 2019-05-01
Series:Platelets
Subjects:
Online Access:http://dx.doi.org/10.1080/09537104.2018.1478402
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author Paul Harrison
M. Angelyn Bethel
Irene Kennedy
Robert Dinsdale
Ruth Coleman
Rury R. Holman
author_facet Paul Harrison
M. Angelyn Bethel
Irene Kennedy
Robert Dinsdale
Ruth Coleman
Rury R. Holman
author_sort Paul Harrison
collection DOAJ
description The antiplatelet efficacy of aspirin (ASA) is reduced in type 2 diabetes (T2D). As the best ex vivo method of measuring ASA efficacy remains uncertain, we compared nine platelet function tests to assess responsiveness to three ASA dosing regimens in 24 T2D patients randomized in a three-treatment crossover design to ASA 100 mg/day, 200 mg/day, or 100 mg twice daily for 2-week treatment periods. Platelet function tests compared were as follows: light transmission aggregometry (LTA)–0.5 mg/mL of arachidonic acid (AA) and 10 µM adenosine diphosphate (ADP); multiplate whole blood aggregometry (WBA)–0.5 mM AA and 6.5 µM ADP; platelet function analyzer (PFA)-100™–collagen and ADP (CADP) and collagen and epinephrine (CEPI); VerifyNow™–ASA; and urinary 11-dehydro-thromboxane B2 (TxB2) and serum TxB2. All cyclo-oxygenase (COX-1)-dependent tests and some COX-1-independent tests (PFA-CEPI, LTA-ADP) demonstrated significant reductions in platelet reactivity with all ASA doses. Two COX-1-independent tests (WBA-ADP and PFA-CADP) showed no overall reduction in platelet reactivity. Overall classifications for detecting all ASA doses, compared to baseline, were as follows: very good–LTA-AA (k = 0.95) and VerifyNow™-ASA (k = 0.85); good–serum TxB2 (k = 0.79); moderate–LTA-ADP (k = 0.59), PFA-100™-CEPI (k = 0.56), urinary TxB2 (k = 0.55), WBA-AA (k = 0.47); and poor–PFA-100™-CADP (k = –0.02) and WBA-ADP (k = –0.07). No significant kappa statistic differences were seen for each test for each ASA dose. Correlations for each test with serum TxB2 measurements were as follows: very good–VerifyNow™-ASA (k = 0.81, R2 = 0.56) and LTA-AA (k = 0.85, R2 = 0.65); good–PFA-100TM-CEPI (k = 0.62, R2 = 0.30); moderate–urinary TxB2 (k = 0.57, R2 = 0.51) and LTA-ADP (k = 0.47, R2 = 0.56); fair–WBA-AA (k = 0.31, R2 = 0.31); and poor–PFA-100™-CADP (k = 0.04, R2 = 0.003) and WBA-ADP (k = –0.04, R2 = 0.0005). The platelet function tests we assessed were not equally effective in measuring the antiplatelet effect of ASA and correlated poorly amongst themselves, but COX-1-dependent tests performed better than non-COX-1-dependent tests.
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spelling doaj.art-470be060714648b3ac5f6116cf1404cb2023-09-15T10:32:00ZengTaylor & Francis GroupPlatelets0953-71041369-16352019-05-0130452152910.1080/09537104.2018.14784021478402Comparison of nine platelet function tests used to determine responses to different aspirin dosages in people with type 2 diabetesPaul Harrison0M. Angelyn Bethel1Irene Kennedy2Robert Dinsdale3Ruth Coleman4Rury R. Holman5University of Birmingham Medical SchoolUniversity of OxfordUniversity of OxfordUniversity of Birmingham Medical SchoolUniversity of OxfordUniversity of OxfordThe antiplatelet efficacy of aspirin (ASA) is reduced in type 2 diabetes (T2D). As the best ex vivo method of measuring ASA efficacy remains uncertain, we compared nine platelet function tests to assess responsiveness to three ASA dosing regimens in 24 T2D patients randomized in a three-treatment crossover design to ASA 100 mg/day, 200 mg/day, or 100 mg twice daily for 2-week treatment periods. Platelet function tests compared were as follows: light transmission aggregometry (LTA)–0.5 mg/mL of arachidonic acid (AA) and 10 µM adenosine diphosphate (ADP); multiplate whole blood aggregometry (WBA)–0.5 mM AA and 6.5 µM ADP; platelet function analyzer (PFA)-100™–collagen and ADP (CADP) and collagen and epinephrine (CEPI); VerifyNow™–ASA; and urinary 11-dehydro-thromboxane B2 (TxB2) and serum TxB2. All cyclo-oxygenase (COX-1)-dependent tests and some COX-1-independent tests (PFA-CEPI, LTA-ADP) demonstrated significant reductions in platelet reactivity with all ASA doses. Two COX-1-independent tests (WBA-ADP and PFA-CADP) showed no overall reduction in platelet reactivity. Overall classifications for detecting all ASA doses, compared to baseline, were as follows: very good–LTA-AA (k = 0.95) and VerifyNow™-ASA (k = 0.85); good–serum TxB2 (k = 0.79); moderate–LTA-ADP (k = 0.59), PFA-100™-CEPI (k = 0.56), urinary TxB2 (k = 0.55), WBA-AA (k = 0.47); and poor–PFA-100™-CADP (k = –0.02) and WBA-ADP (k = –0.07). No significant kappa statistic differences were seen for each test for each ASA dose. Correlations for each test with serum TxB2 measurements were as follows: very good–VerifyNow™-ASA (k = 0.81, R2 = 0.56) and LTA-AA (k = 0.85, R2 = 0.65); good–PFA-100TM-CEPI (k = 0.62, R2 = 0.30); moderate–urinary TxB2 (k = 0.57, R2 = 0.51) and LTA-ADP (k = 0.47, R2 = 0.56); fair–WBA-AA (k = 0.31, R2 = 0.31); and poor–PFA-100™-CADP (k = 0.04, R2 = 0.003) and WBA-ADP (k = –0.04, R2 = 0.0005). The platelet function tests we assessed were not equally effective in measuring the antiplatelet effect of ASA and correlated poorly amongst themselves, but COX-1-dependent tests performed better than non-COX-1-dependent tests.http://dx.doi.org/10.1080/09537104.2018.1478402aspirinplatelet functiontype 2 diabetes
spellingShingle Paul Harrison
M. Angelyn Bethel
Irene Kennedy
Robert Dinsdale
Ruth Coleman
Rury R. Holman
Comparison of nine platelet function tests used to determine responses to different aspirin dosages in people with type 2 diabetes
Platelets
aspirin
platelet function
type 2 diabetes
title Comparison of nine platelet function tests used to determine responses to different aspirin dosages in people with type 2 diabetes
title_full Comparison of nine platelet function tests used to determine responses to different aspirin dosages in people with type 2 diabetes
title_fullStr Comparison of nine platelet function tests used to determine responses to different aspirin dosages in people with type 2 diabetes
title_full_unstemmed Comparison of nine platelet function tests used to determine responses to different aspirin dosages in people with type 2 diabetes
title_short Comparison of nine platelet function tests used to determine responses to different aspirin dosages in people with type 2 diabetes
title_sort comparison of nine platelet function tests used to determine responses to different aspirin dosages in people with type 2 diabetes
topic aspirin
platelet function
type 2 diabetes
url http://dx.doi.org/10.1080/09537104.2018.1478402
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