ADAMTS13 activity, neutrophil extracellular traps(NETs) and platelet functional capacity in patients with strokes from different etiologies.

H. S. Bölting, M. Rumpf, R. Dittrich, J. Minnerup, L. Schuengel, M. F. Brodde, M. Ritter, B. E. Kehrel (Muenster, Germany)

Vascular Wall
Date: 17.02.2017,
Time: 08:00 - 09:15

Objective: Ischemic stroke is a thrombo-inflammatory disease. Platelets are not only regulators of haemostasis, but are also involved in inflammation. However little is still known about the pathophysiological role of platelets in stroke. Therefore ADAMTS13 activity, neutrophil extracellular trap (NET) formation and platelet functional capacity were analyzed in patients with acute strokes from different origins.

Methods: Blood from fifty-eight (58) patients with acute strokes, admitted to the stroke unit of the university hospital during their inpatient stay, and 19 healthy matched controls without any vascular disease were studied. Of these patients 25 were diagnosed to suffer from cardio-embolic stroke (CES), 23 had severe ACI stenosis and 10 micro-angiopathic stroke (MAS). Platelet variables were measured in the acute phase (<4days after stroke) of cerebral ischemia and compared with control variables. Platelet and neutrophil activation status was measured by flow cytometry, platelet functional capacity to respond to thrombin, in the presence of GPRP, and to collagen was detected by fibrinogen binding, GPIIbIIIa activation epitope expression as well as expression of the secretion markers CD62P and CD63. Myeloperoxidase, sP-selectin, and NET formation in plasma were measured by ELISA. ADAMTS13 activity was measured by FRETS-VWF86 assay.

Results: Platelet CD63 and CD62P expression and plasma sP-selectin was higher after stroke compared with healthy controls. This was especially pronounced in patients with cardio-embolic and micro-angiopathic stroke. The uptake of mepacrine into platelet’s dense granule of stroke patients was significantly diminished, corresponding to less mepacrine secretion induced by platelet activation. Reduced response to collagen and thrombin was accompanied by decreased expression of the collagen receptor GPVI and epitope for the thrombin-binding site on PAR-1. All stroke patients had significantly higher levels of myeloperoxidase and of NETs in plasma in comparison to healthy controls, with the highest MPO and NET levels in plasma of patients with CES. The activity of ADAMTS13 was significantly lower in patients with CES than in healthy controls (p<0,002) or patients from MAS or severe ACI stenosis.

Conclusion: Platelet and neutrophil associated mechanisms may offer novel insights to understand stroke with different etiologies.