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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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; Harrison, Paul; Brown, Martin M.; Sidhu, Paul S.; Mackie, Ian J.; Scully, Marie; Machin, Samuel J.

In: Journal of the Neurological Sciences, Vol. 348, No. 1-2, 15.01.2015, p. 35-40.

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Mccabe, Dominick J.h. ; Murphy, Stephen J.x. ; Starke, Richard ; Harrison, Paul ; Brown, Martin M. ; Sidhu, Paul S. ; Mackie, Ian J. ; Scully, Marie ; Machin, Samuel J. / Relationship between ADAMTS13 activity, von Willebrand factor antigen levels and platelet function in the early and late phases after TIA or ischaemic stroke. In: Journal of the Neurological Sciences. 2015 ; Vol. 348, No. 1-2. pp. 35-40.

Bibtex

@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",

}

RIS

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

VL - 348

SP - 35

EP - 40

JO - Journal of the Neurological Sciences

JF - Journal of the Neurological Sciences

SN - 0022-510X

IS - 1-2

ER -