Chronic hyper-reactivity of platelets resulting in enhanced monocyte recruitment in patients after ischaemic stroke

Abstract

Although the platelet activation profile after stroke is a well-known issue, the platelet reactivity assessed prospectively after ischaemic stroke still remains equivocal. The aim of this study was to evaluate the reactivity of platelets in response to stimulation with thrombin receptor-activating peptide (TRAP) at 1, 10 and 90 days after ischaemic stroke and to compare it with results obtained in control groups. We determined the increment in surface expression of CD62P, CD40L and monocyte- and granulocyte-platelet aggregate formation using five-colour flow cytometry in 86 subjects after an ischaemic event, in 62 disease controls, and in 38 healthy volunteers. We assessed the plasma levels of CD62P and CD40L soluble forms. In patients after stroke a significantly lower increment in CD62P surface expression (p < 0.01) and higher increments in both CD40L platelet surface expression (p < 0.01) and monocyte-platelet aggregate percentage (p < 0.01) were found at every studied time point, as compared with the control groups. Plasma levels of soluble CD62P (sCD62P) and soluble CD40L (sCD40L) were increased in stroke subjects in both the acute and the subacute phase of the stroke and they dropped to levels observed in controls at day 90 after the ischaemic incident. In all studied groups a positive correlation was noted between plasma levels of sCD62P and sCD40L. In conclusion, while at 3-month follow-up the levels of soluble forms normalize in stroke patients, the profile of platelet reactivity in response to activation with TRAP differs from that observed in the controls despite the secondary stroke prevention.

Platelets and acute cerebral infarction

“…Ample evidence testifies the effectiveness of aspirin for reducing stroke recurrence [30]. With a few exceptions [6,23], previous work has revealed enhanced reactivity and increased platelet activity in acute stroke [19]. It, therefore, appears that the findings of this study are not consistent with earlier science or with up-to-date clinical practice.…”

“…Conflicting data further exists with respect to circulating P-selectin. In acute stroke, concentrations of the protein appear to increase [6]. Still, other scientists have been unable to demonstrate soluble P-selectin alterations in stroke [25].…”

“…Early aggregation studies show augmented platelet reactivity in acute stroke [15]. Other scientists have demonstrated an absence of alterations or even a decline in platelet reactivity in conjunction with acute cerebral infarction [6]. Obviously, increased platelet size signifying greater reactivity, is a feature of stroke sufferers [16].…”

“…Fibrinogen binds to the latter receptor allowing platelets to aggregate [5]. The inflammatory response is stimulated as well and involves substantial platelet-leukocyte cross talk [6]. Initial interactions between platelets and white cells are attributed primarily to the platelet surface-bound adhesion receptor P-selectin [7].…”

New prognostic biomarkers in patients with ischemic stroke

“…CD154 is released into blood circulation as soluble CD154 (sCD154) [37] . When sCD154 binding to their cell surface receptor then exhibit proinflammatory and procoagulant properties, due that triggers the expression of interleukin (IL)-1, IL-6, IL-12, TNF-alpha, interferon-gamma [38] , tissue factor [39][40][41][42] , and binding to the glycoprotein IIb/IIIa platelet receptor [43,44] .There have been found a higher CD154 expression in platelet of ischemic stroke patients than in controls subjects [45,46] , higher circulating levels of sCD154 in ischemic stroke patients than in controls subjects [47][48][49][50][51][52][53][54] , and a higher CD154 expression in platelet of ischemic stroke patients with poor functional outcome compared with patients with better outcome [55,56] .In a study by our team were found higher serum levels of sCD154 in MMCAI patients than in healthy subjects [57] . In addition, we found an association between circulating levels of sCD154 and severity of stroke assessed by GCS (p = 0.04) for the first time.…”