Relationship between ADAMTS13 activity, von Willebrand factor antigen levels and platelet function in the early and late phases after TIA or ischaemic stroke

Dominick J.h. Mccabe; Stephen J.x. Murphy; Richard Starke; Paul Harrison; Martin M. Brown; Paul S. Sidhu; Ian J. Mackie; Marie Scully; Samuel J. Machin

doi:10.1016/j.jns.2014.10.035

Relationship between ADAMTS13 activity, von Willebrand factor antigen levels and platelet function in the early and late phases after TIA or ischaemic stroke

Dominick J.h. Mccabe, Stephen J.x. Murphy, Richard Starke, Paul Harrison, Martin M. Brown, Paul S. Sidhu, Ian J. Mackie, Marie Scully, Samuel J. Machin

Immunology and Immunotherapy

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Abstract

BACKGROUND: Reduced ADAMTS13 activity is seen in thrombotic thrombocytopenic purpura (TTP), and may lead to accumulation of prothrombotic ultra-large von Willebrand factor (ULVWF) multimers in vivo. ADAMTS13 activity and its relationship with VWF antigen (VWF:Ag) levels and platelet function in 'non-TTP related' TIA or ischaemic stroke has not been comprehensively studied.

METHODS: In this prospective pilot observational analytical case-control study, ADAMTS13 activity and VWF:Ag levels were quantified in platelet poor plasma in 53 patients in the early phase (≤ 4 weeks) and 34 of these patients in the late phase (≥ 3 months) after TIA or ischaemic stroke on aspirin. Data were compared with those from 22 controls not on aspirin. The impact of ADAMTS13 on platelet function in whole blood was quantified by measuring Collagen-ADP (C-ADP) and Collagen-Epinephrine closure times on a platelet function analyser (PFA-100(®)).

RESULTS: Median ADAMTS13 activity was significantly reduced in the early phase (71.96% vs. 95.5%, P <0.01) but not in the late phase after TIA or stroke compared with controls (86.3% vs. 95.5%, P=0.19). There was a significant inverse relationship between ADAMTS13 activity and VWF:Ag levels in the early phase (r=-0.31; P=0.024), but not in the late phase after TIA or stroke (P=0.74). There was a positive correlation between ADAMTS13 activity and C-ADP closure times in early phase patients only, likely mediated via VWF:Ag levels.

DISCUSSION: ADAMTS13 activity is reduced and VWF:Ag expression is increased within 4 weeks of TIA or ischaemic stroke onset, and can promote enhanced platelet adhesion and aggregation in response to stimulation with collagen and ADP via VWF-mediated pathways. These data improve our understanding of the dynamic haemostatic and thrombotic profiles of ischaemic cerebrovascular disease (CVD) patients, and are important in view of the potential future role that ADAMTS13 may have to play as an anti-thrombotic agent in CVD.

Original language	English
Pages (from-to)	35-40
Number of pages	6
Journal	Journal of the Neurological Sciences
Volume	348
Issue number	1-2
Early online date	31 Oct 2014
DOIs	https://doi.org/10.1016/j.jns.2014.10.035
Publication status	Published - 15 Jan 2015

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10.1016/j.jns.2014.10.035

Dominik_et_al_Relationship_between_ADAMTS13_activity_Journal_Neurological_Sciences_2014
NOTICE: this is the author’s version of a work that was accepted for publication in Journal of the Neurological Sciences. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Journal of the Neurological Sciences, Vol 348, Issue 1-2, January 2015, DOI: 10.1016/j.jns.2014.10.035. Eligibility for the repository checked March 2015
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Mccabe, D. J. H., Murphy, S. J. X., Starke, R., Harrison, P., Brown, M. M., Sidhu, P. S., Mackie, I. J., Scully, M., & Machin, S. J. (2015). Relationship between ADAMTS13 activity, von Willebrand factor antigen levels and platelet function in the early and late phases after TIA or ischaemic stroke. Journal of the Neurological Sciences, 348(1-2), 35-40. https://doi.org/10.1016/j.jns.2014.10.035

@article{826e1866f68740c68b41845b9a593dfd,

title = "Relationship between ADAMTS13 activity, von Willebrand factor antigen levels and platelet function in the early and late phases after TIA or ischaemic stroke",

abstract = "BACKGROUND: Reduced ADAMTS13 activity is seen in thrombotic thrombocytopenic purpura (TTP), and may lead to accumulation of prothrombotic ultra-large von Willebrand factor (ULVWF) multimers in vivo. ADAMTS13 activity and its relationship with VWF antigen (VWF:Ag) levels and platelet function in 'non-TTP related' TIA or ischaemic stroke has not been comprehensively studied.METHODS: In this prospective pilot observational analytical case-control study, ADAMTS13 activity and VWF:Ag levels were quantified in platelet poor plasma in 53 patients in the early phase (≤ 4 weeks) and 34 of these patients in the late phase (≥ 3 months) after TIA or ischaemic stroke on aspirin. Data were compared with those from 22 controls not on aspirin. The impact of ADAMTS13 on platelet function in whole blood was quantified by measuring Collagen-ADP (C-ADP) and Collagen-Epinephrine closure times on a platelet function analyser (PFA-100({\textregistered})).RESULTS: Median ADAMTS13 activity was significantly reduced in the early phase (71.96% vs. 95.5%, P <0.01) but not in the late phase after TIA or stroke compared with controls (86.3% vs. 95.5%, P=0.19). There was a significant inverse relationship between ADAMTS13 activity and VWF:Ag levels in the early phase (r=-0.31; P=0.024), but not in the late phase after TIA or stroke (P=0.74). There was a positive correlation between ADAMTS13 activity and C-ADP closure times in early phase patients only, likely mediated via VWF:Ag levels.DISCUSSION: ADAMTS13 activity is reduced and VWF:Ag expression is increased within 4 weeks of TIA or ischaemic stroke onset, and can promote enhanced platelet adhesion and aggregation in response to stimulation with collagen and ADP via VWF-mediated pathways. These data improve our understanding of the dynamic haemostatic and thrombotic profiles of ischaemic cerebrovascular disease (CVD) patients, and are important in view of the potential future role that ADAMTS13 may have to play as an anti-thrombotic agent in CVD.",

author = "Mccabe, {Dominick J.h.} and Murphy, {Stephen J.x.} and Richard Starke and Paul Harrison and Brown, {Martin M.} and Sidhu, {Paul S.} and Mackie, {Ian J.} and Marie Scully and Machin, {Samuel J.}",

year = "2015",

month = jan,

day = "15",

doi = "10.1016/j.jns.2014.10.035",

language = "English",

volume = "348",

pages = "35--40",

journal = "Journal of the Neurological Sciences",

issn = "0022-510X",

publisher = "Elsevier",

number = "1-2",

}

Mccabe, DJH, Murphy, SJX, Starke, R, Harrison, P, Brown, MM, Sidhu, PS, Mackie, IJ, Scully, M & Machin, SJ 2015, 'Relationship between ADAMTS13 activity, von Willebrand factor antigen levels and platelet function in the early and late phases after TIA or ischaemic stroke', Journal of the Neurological Sciences, vol. 348, no. 1-2, pp. 35-40. https://doi.org/10.1016/j.jns.2014.10.035

Relationship between ADAMTS13 activity, von Willebrand factor antigen levels and platelet function in the early and late phases after TIA or ischaemic stroke. / Mccabe, Dominick J.h.; Murphy, Stephen J.x.; Starke, Richard et al.
In: Journal of the Neurological Sciences, Vol. 348, No. 1-2, 15.01.2015, p. 35-40.

Research output: Contribution to journal › Article › peer-review

TY - JOUR

T1 - Relationship between ADAMTS13 activity, von Willebrand factor antigen levels and platelet function in the early and late phases after TIA or ischaemic stroke

AU - Mccabe, Dominick J.h.

AU - Murphy, Stephen J.x.

AU - Starke, Richard

AU - Harrison, Paul

AU - Brown, Martin M.

AU - Sidhu, Paul S.

AU - Mackie, Ian J.

AU - Scully, Marie

AU - Machin, Samuel J.

PY - 2015/1/15

Y1 - 2015/1/15

N2 - BACKGROUND: Reduced ADAMTS13 activity is seen in thrombotic thrombocytopenic purpura (TTP), and may lead to accumulation of prothrombotic ultra-large von Willebrand factor (ULVWF) multimers in vivo. ADAMTS13 activity and its relationship with VWF antigen (VWF:Ag) levels and platelet function in 'non-TTP related' TIA or ischaemic stroke has not been comprehensively studied.METHODS: In this prospective pilot observational analytical case-control study, ADAMTS13 activity and VWF:Ag levels were quantified in platelet poor plasma in 53 patients in the early phase (≤ 4 weeks) and 34 of these patients in the late phase (≥ 3 months) after TIA or ischaemic stroke on aspirin. Data were compared with those from 22 controls not on aspirin. The impact of ADAMTS13 on platelet function in whole blood was quantified by measuring Collagen-ADP (C-ADP) and Collagen-Epinephrine closure times on a platelet function analyser (PFA-100(®)).RESULTS: Median ADAMTS13 activity was significantly reduced in the early phase (71.96% vs. 95.5%, P <0.01) but not in the late phase after TIA or stroke compared with controls (86.3% vs. 95.5%, P=0.19). There was a significant inverse relationship between ADAMTS13 activity and VWF:Ag levels in the early phase (r=-0.31; P=0.024), but not in the late phase after TIA or stroke (P=0.74). There was a positive correlation between ADAMTS13 activity and C-ADP closure times in early phase patients only, likely mediated via VWF:Ag levels.DISCUSSION: ADAMTS13 activity is reduced and VWF:Ag expression is increased within 4 weeks of TIA or ischaemic stroke onset, and can promote enhanced platelet adhesion and aggregation in response to stimulation with collagen and ADP via VWF-mediated pathways. These data improve our understanding of the dynamic haemostatic and thrombotic profiles of ischaemic cerebrovascular disease (CVD) patients, and are important in view of the potential future role that ADAMTS13 may have to play as an anti-thrombotic agent in CVD.

AB - BACKGROUND: Reduced ADAMTS13 activity is seen in thrombotic thrombocytopenic purpura (TTP), and may lead to accumulation of prothrombotic ultra-large von Willebrand factor (ULVWF) multimers in vivo. ADAMTS13 activity and its relationship with VWF antigen (VWF:Ag) levels and platelet function in 'non-TTP related' TIA or ischaemic stroke has not been comprehensively studied.METHODS: In this prospective pilot observational analytical case-control study, ADAMTS13 activity and VWF:Ag levels were quantified in platelet poor plasma in 53 patients in the early phase (≤ 4 weeks) and 34 of these patients in the late phase (≥ 3 months) after TIA or ischaemic stroke on aspirin. Data were compared with those from 22 controls not on aspirin. The impact of ADAMTS13 on platelet function in whole blood was quantified by measuring Collagen-ADP (C-ADP) and Collagen-Epinephrine closure times on a platelet function analyser (PFA-100(®)).RESULTS: Median ADAMTS13 activity was significantly reduced in the early phase (71.96% vs. 95.5%, P <0.01) but not in the late phase after TIA or stroke compared with controls (86.3% vs. 95.5%, P=0.19). There was a significant inverse relationship between ADAMTS13 activity and VWF:Ag levels in the early phase (r=-0.31; P=0.024), but not in the late phase after TIA or stroke (P=0.74). There was a positive correlation between ADAMTS13 activity and C-ADP closure times in early phase patients only, likely mediated via VWF:Ag levels.DISCUSSION: ADAMTS13 activity is reduced and VWF:Ag expression is increased within 4 weeks of TIA or ischaemic stroke onset, and can promote enhanced platelet adhesion and aggregation in response to stimulation with collagen and ADP via VWF-mediated pathways. These data improve our understanding of the dynamic haemostatic and thrombotic profiles of ischaemic cerebrovascular disease (CVD) patients, and are important in view of the potential future role that ADAMTS13 may have to play as an anti-thrombotic agent in CVD.

U2 - 10.1016/j.jns.2014.10.035

DO - 10.1016/j.jns.2014.10.035

M3 - Article

C2 - 25498844

SN - 0022-510X

VL - 348

SP - 35

EP - 40

JO - Journal of the Neurological Sciences

JF - Journal of the Neurological Sciences

IS - 1-2

ER -

Relationship between ADAMTS13 activity, von Willebrand factor antigen levels and platelet function in the early and late phases after TIA or ischaemic stroke

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