Platelet P-selectin levels in relation to plasma soluble P-selectin and beta-thromboglobulin levels in atrial fibrillation.
OBJECTIVE
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 beta-thromboglobulin as established indices of platelet activation. METHODSMDSAH: We studied 122 patients (mean [SD] age, 71 [9] years; 65 men) with chronic AF of >6 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 beta-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 (P=0.03) than in healthy controls, but sP-selectin and beta-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 (P<0.05). pP-selectin/sP-selectin correlated significantly in healthy controls (r=0.47, P=0.03) but inversely (r=-0.43, P=0.03) 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.
Kamath
Sridhar
S
Haemostasis, Thrombosis, and Vascular Biology Unit, University Department of Medicine, City Hospital, Birmingham, UK.
Blann
Andrew D
AD
Caine
Graham J
GJ
Gurney
David
D
Chin
Bernard S P
BS
Lip
Gregory Y H
GY
D000368:Aged; D000925:Anticoagulants / Q000627:therapeutic use; D001241:Aspirin / Q000627:therapeutic use; D001281:Atrial Fibrillation / Q000097:blood / Q000188:drug therapy / Q000378:metabolism*; D001792:Blood Platelets / Q000737:chemistry / Q000378:metabolism*; D002452:Cell Count; D002908:Chronic Disease; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D008297:Male; D017830:Octoxynol / Q000737:chemistry; D019007:P-Selectin / Q000032:analysis / Q000097:blood / Q000378:metabolism*; D011237:Predictive Value of Tests; D012016:Reference Values; D014859:Warfarin / Q000627:therapeutic use; D001620:beta-Thromboglobulin / Q000032:analysis / Q000378:metabolism*
D000925:Anticoagulants; D019007:P-Selectin; D001620:beta-Thromboglobulin; D014859:Warfarin; D017830:Octoxynol; D001241:Aspirin