title: Fibrin clot structure and platelet aggregation in patients with aspirin treatment failure.
abstract: BACKGROUND
  Aspirin is a cornerstone in prevention of cardiovascular events and modulates both platelet aggregation and fibrin clot formation. Some patients experience cardiovascular events whilst on aspirin, often termed aspirin treatment failure (ATF). This study evaluated both platelet aggregation and fibrin clot structure in patients with ATF.
  
  
  METHODS
  We included 177 stable coronary artery disease patients on aspirin monotherapy. Among these, 116 (66%) had ATF defined as myocardial infarction (MI) whilst on aspirin. Platelet aggregation was assessed by Multiplate® aggregometry and VerifyNow®, whereas turbidimetric assays and scanning electron microscopy were employed to study fibrin clot characteristics.
  
  
  RESULTS
  Enhanced platelet aggregation was observed in patients with ATF compared with non-MI patients following stimulation with arachidonic acid 1.0 mM (median 161 (IQR 95; 222) vs. 97 (60; 1776) AU*min, p = 0.005) and collagen 1.0 µg/mL (293 (198; 427) vs. 220 (165; 370) AU*min, p = 0.03). Similarly, clot maximum absorbance, a measure of fibrin network density, was increased in patients with ATF (0.48 (0.41; 0.52) vs. 0.42 (0.38; 0.50), p = 0.02), and this was associated with thinner fibres (mean ± SD: 119.7±27.5 vs. 127.8±31.1 nm, p = 0.003) and prolonged lysis time (552 (498; 756) vs. 519 (468; 633) seconds; p = 0.02). Patients with ATF also had increased levels of C-reactive protein (CRP) (1.34 (0.48; 2.94) and 0.88 (0.32; 1.77) mg/L, p = 0.01) compared with the non-MI group. Clot maximum absorbance correlated with platelet aggregation (r = 0.31-0.35, p-values<0.001) and CRP levels (r = 0.60, p<0.001).
  
  
  CONCLUSIONS
  Patients with aspirin treatment failure showed increased platelet aggregation and altered clot structure with impaired fibrinolysis compared with stable CAD patients without previous MI. These findings suggest that an increased risk of aspirin treatment failure may be identified by measuring both platelet function and fibrin clot structure.
authors: Department of Cardiology, Aarhus University Hospital, Aarhus, Denmark ; Division of Cardiovascular and Diabetes Research, Leeds Institute for Genetics, Health and Therapeutics, University of Leeds, Leeds, United Kingdom.
authors: Søs
authors: S
authors: Neergaard-Petersen
authors: Ramzi
authors: R
authors: Ajjan
authors: Anne-Mette
authors: AM
authors: Hvas
authors: Katharina
authors: K
authors: Hess
authors: Sanne Bøjet
authors: SB
authors: Larsen
authors: Steen Dalby
authors: SD
authors: Kristensen
authors: Erik Lerkevang
authors: EL
authors: Grove
mesh_terms: D000368:Aged; D001241:Aspirin / Q000627:therapeutic use*; D001777:Blood Coagulation; D001792:Blood Platelets / Q000378:metabolism / Q000473:pathology*; D002097:C-Reactive Protein / Q000378:metabolism; D003324:Coronary Artery Disease / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D005260:Female; D005337:Fibrin / Q000648:ultrastructure*; D006801:Humans; D008297:Male; D008855:Microscopy, Electron, Scanning; D008875:Middle Aged; D009203:Myocardial Infarction / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D015539:Platelet Activation; D010974:Platelet Aggregation; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use*; D010979:Platelet Function Tests; D017211:Treatment Failure
chemical_list: D010975:Platelet Aggregation Inhibitors; D005337:Fibrin; D002097:C-Reactive Protein; D001241:Aspirin
references: Thromb Res. 2010 Oct;126(4):e318-22
references: 20451957
references: Arterioscler Thromb Vasc Biol. 2009 May;29(5):712-7
references: 19286636
references: Eur Heart J. 2009 Feb;30(4):426-35
references: 19174428
references: J Thromb Haemost. 2007 Sep;5(9):1988-90
references: 17723142
references: J Clin Endocrinol Metab. 2012 May;97(5):1463-73
references: 22378816
references: Arterioscler Thromb Vasc Biol. 2010 Jan;30(1):75-9
references: 19815816
references: J Biol Chem. 2007 Jan 5;282(1):710-20
references: 17090548
references: J Thromb Haemost. 2011 Jan;9(1):185-91
references: 20955349
references: Arterioscler Thromb Vasc Biol. 2004 Sep;24(9):1558-66
references: 15217804
references: Thromb Haemost. 2005 Nov;94(5):1048-53
references: 16363249
references: Diabetologia. 2005 Jun;48(6):1198-206
references: 15864538
references: Arterioscler Thromb Vasc Biol. 2007 Dec;27(12):2783-9
references: 17932316
references: J Thromb Thrombolysis. 2012 May;33(4):349-54
references: 22189756
references: Curr Pharm Des. 2012;18(33):5344-61
references: 22724409
references: Arterioscler Thromb Vasc Biol. 2011 Jul;31(7):1696-702
references: 21617138
references: Curr Pharm Des. 2012;18(33):5197-214
references: 22724408
references: Circulation. 2002 Oct 8;106(15):1938-42
references: 12370216
references: Thromb Haemost. 2012 Jul;108(1):140-7
references: 22534977
references: Blood. 2010 May 13;115(19):3980-8
references: 20228273
references: Thromb Res. 1980 Feb 1-15;17(3-4):317-27
references: 7368167
references: Atherosclerosis. 2006 Jun;186(2):240-59
references: 16343508
references: Arterioscler Thromb Vasc Biol. 2006 Nov;26(11):2567-73
references: 16917107
references: Curr Pharm Des. 2012;18(33):5379-91
references: 22724414
references: Thromb Res. 2012 Jan;129(1):56-61
references: 21917303
references: Pharmacoepidemiol Drug Saf. 2008 Aug;17(8):753-9
references: 18613215
references: Thromb Haemost. 2012 Jun;107(6):1092-9
references: 22476576
references: Atherosclerosis. 2008 Feb;196(2):551-7
references: 17640649
references: Thromb Haemost. 2010 Jun;103(6):1245-53
references: 20352155
references: Eur Heart J. 2011 Dec;32(23):2999-3054
references: 21873419
references: Arterioscler Thromb Vasc Biol. 2000 May;20(5):1354-61
references: 10807754
references: J Cardiovasc Pharmacol. 2009 Jan;53(1):24-9
references: 19129740
references: Nat Clin Pract Cardiovasc Med. 2007 Jan;4(1):42-50
references: 17180149
references: BMJ. 2002 Jan 12;324(7329):71-86
references: 11786451
references: Angiology. 2006 Oct-Nov;57(5):607-14
references: 17067984
references: J Atheroscler Thromb. 2010 Feb;17(1):1-11
references: 20032572
references: Nephrol Dial Transplant. 2008 Jun;23(6):2010-5
references: 18156458
references: BMJ. 2008 Jan 26;336(7637):195-8
references: 18202034
references: Diabetologia. 2006 May;49(5):1071-80
references: 16538489