Platelet P-Selectin Levels in Relation to Plasma Soluble P-Selectin and β-Thromboglobulin Levels in Atrial Fibrillation

Abstract

Background and Purpose-The increased risk of stroke and thromboembolism in atrial fibrillation (AF) may be related to a prothrombotic or hypercoagulable state, with abnormalities of hemostasis and platelet activation. To investigate the role of platelets in AF and the influence of antithrombotic therapy, we developed and then applied a new assay to detect the absolute amount of P-selectin per platelet (pP-selectin) based on cell lysis. Thus, pP-selectin in AF patients was compared with that of healthy controls and also with plasma soluble P-selectin (sP-selectin) and ␤-thromboglobulin as established indices of platelet activation. Methods-We studied 122 patients (mean [SD] age, 71 [9] years; 65 men) with chronic AF of Ͼ6 weeks' duration: 34 were not on antithrombotic therapy, 30 were taking aspirin (75 to 300 mg/d), and 58 were fully anticoagulated with warfarin. pP-selectin was compared with sP-selectin and plasma ␤-thromboglobulin levels (enzyme-linked immunosorbent assay). Results were compared with those of 23 healthy controls (mean [SD] age, 74 [9] years; 7 men) in sinus rhythm. Results-pP-selectin was significantly lower in AF patients on no antithrombotic therapy (Pϭ0.03) than in healthy controls, but sP-selectin and ␤-thromboglobulin levels were not significantly different and did not differ in patients taking aspirin or warfarin. However, pP-selectin was lower in patients with AF on aspirin than in those on warfarin (PϽ0.05). pP-selectin/sP-selectin correlated significantly in healthy controls (rϭ0.47, Pϭ0.03) but inversely (rϭϪ0.43, Pϭ0.03) in AF patients on no antithrombotic therapy. Conclusions-Lower levels of pP-selectin may represent a depletion of pP-selectin after platelet activation in AF. Aspirin further decreases pP-selectin levels compared with warfarin. On the basis of the principle of platelet lysis, we demonstrate that it is possible to determine the amount of P-selectin per platelet, which may be regulated in the megakaryocyte through a cyclooxygenase-dependent pathway.

Platelet indexes in relation to target organ damage in high-risk hypertensive patients

“…The lower limit of sensitivity of the assay was 0.8 ng/ml. Levels of pP-sel were measured by a lysate technique, as previously described in detail (20). Briefly, platelet-rich plasma was obtained by centrifugation of venous blood at 200g for 10 min.…”

“…However, the amount of P-selectin in a particular platelet (pP-sel) has not been extensively studied in hypertension, because, until recently, the main method of estimating expression of P-selectin has been by flow cytometry (14) or whole platelet enzyme-linked immunosorbent assay (ELISA) (15). We have recently reported a novel method of quantifying total pP-sel levels by lysing a set number of platelets with the detergent Triton X-100 and measuring P-selectin by ELISA in the resultant lysate (16). Finally, advances in flow cytometry have enabled the development of additional measures of platelet biology, not only mean platelet volume (MPV), but also platelet mass and component/granularity, and although the precise pathophysiologic implications of these three indexes is unclear, they may have a role in unstable angina and acute MI (17).…”

Impairment of the Vasodilatation Capability of the Brachial Artery in Patients with Idiopathic Venous Thrombosis

“…There are also contradictory data on the influence of warfarin treatment on selectin levels. Kamath and colleagues found no difference in soluble P-selectin levels in patients with atrial fibrillation but not on therapy compared to those treated with aspirin or warfarin 39) . Therefore, it seems unlikely that the difference in levels of P-selectin between controls and patients with idiopathic VT in our study could be influenced by treatment with warfarin.…”

Determinants of Infarction Patterns in Cardioembolic Stroke

“…Platelet-associated intrinsic procoagulant activities are relevant during this phase [16]. Previous work has shown that platelet activity was lowest among patients who reported prior use of aspirin [17]. This suggests that the roles of platelet-associated intrinsic procoagulant activities during the formation and growth of the thrombus in the cardiac chamber may explain why small or fragmented thrombi were more frequent among patients with a prior history of use of antiplatelet medication.…”