A study of platelet activation in atrial fibrillation and the effects of antithrombotic therapy.
BACKGROUND
Platelet function may be abnormal in patients with atrial fibrillation (AF) and could be related to abnormal thrombogenesis. The aim of this cross-sectional study was to investigate new aspects of platelet biology in AF, predominantly focusing on platelet activation and the effects of concomitant antiplatelet and anticoagulant therapy.


METHODS
The study group of 238 patients were (i). 93 patients on no antithrombotic therapy, (ii). 60 patients taking 75-325 mg aspirin/day, and (iii). 85 patients on dose-adjusted warfarin (International Normalised Ratio [INR] range 2.0-3.0). Results were compared with those from 50 age- and sex-matched normal subjects. Platelet markers (plasma beta-thromboglobulin, soluble glycoprotein V [both ELISA]), coagulation markers (fibrin D-dimer [ELISA] and fibrinogen [Clauss]), and platelet aggregation in response to standard platelet agonists were studied.


RESULTS
beta-thromboglobulin (P=0.01), soluble glycoprotein V (P<0.001) and fibrin D-dimer (P=0.002) were higher in untreated AF patients compared to healthy controls. AF patients on warfarin had lower fibrin D-dimer (P<0.001) when compared to AF patients on no therapy. Plasma fibrinogen and platelet aggregation was no different between patients with AF and healthy controls. Aspirin use was associated with reduced platelet aggregation response to epinephrine (P=0.01), whilst patients established on warfarin had significantly lower plasma fibrin D-dimer levels.


CONCLUSIONS
AF patients exhibit changes in plasma markers of platelet function but no significant abnormalities of platelet aggregation. However, treatment with warfarin or aspirin failed to demonstrate any significant benefit on platelet activation, although warfarin use was associated with reduced thrombogenesis (fibrin D-dimer). We suggest that platelet activation may not play an important role in the pathogenesis of thromboembolism in AF.
Kamath
S
S
Haemostasis Thrombosis and Vascular Biology Unit, University Department of Medicine, City Hospital, Birmingham, UK.
Blann
A D
AD
Chin
B S P
BS
Lanza
F
F
Aleil
B
B
Cazenave
J P
JP
Lip
G Y H
GY
D000368:Aged; D000925:Anticoagulants / Q000627:therapeutic use*; D001241:Aspirin / Q000627:therapeutic use*; D001281:Atrial Fibrillation / Q000188:drug therapy* / Q000503:physiopathology; D003430:Cross-Sectional Studies; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005260:Female; D005338:Fibrin Fibrinogen Degradation Products / Q000032:analysis; D006023:Glycoproteins / Q000032:analysis; D006801:Humans; D008297:Male; D015999:Multivariate Analysis; D015539:Platelet Activation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use*; D014859:Warfarin / Q000627:therapeutic use*; D001620:beta-Thromboglobulin / Q000032:analysis
D000925:Anticoagulants; D005338:Fibrin Fibrinogen Degradation Products; D006023:Glycoproteins; D010975:Platelet Aggregation Inhibitors; D001620:beta-Thromboglobulin; C036309:fibrin fragment D; D014859:Warfarin; D001241:Aspirin