Relationship between ADAMTS13 activity, von Willebrand factor antigen levels and platelet function in the early and late phases after TIA or ischaemic stroke (P5.128)

OBJECTIVE: To investigate the relationship between ADAMTS13 activity and its relationship with VWF antigen(VWF:Ag) levels and platelet function in ‘non-TTP related’ TIA or ischaemic stroke. 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. It’s effects in cerebrovascular disease have not been extensively studied. DESIGN/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 (蠅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 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[percnt] vs. 95.5[percnt], P <0.01) but not in the late phase after TIA or stroke compared with controls (86.3[percnt] vs. 95.5[percnt], 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. CONCLUSIONS: 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/thrombotic profiles of ischaemic cerebrovascular disease(CVD) patients, and are important in view of the potential future role of ADAMTS13 as a novel antithrombotic agent in CVD Disclosure: Dr. Murphy has nothing to disclose. Dr. Starke has nothing to disclose. Dr. Harrison has nothing to disclose. Dr. Brown has nothing to disclose. Dr. Sidhu has nothing to disclose. Dr. Mackie has nothing to disclose. Dr. Scully has nothing to disclose. Dr. Machin has nothing to disclose. Dr. Mccabe has nothing to disclose.