Plasma and whole blood clot strength measured by thrombelastography in patients treated with clopidogrel during acute coronary syndromes.
BACKGROUND
Treatment with clopidogrel, a selective platelet P2Y12 receptor antagonist, reduces risk of recurrent ischemic events in patients with acute coronary syndrome (ACS), by limiting platelet aggregation and activation. Stable whole blood clot formation requires activation of platelets, generation of fibrin and final fibrin crosslinks. In this study we intended to compare plasma and whole blood thrombelastography (TEG) measurements in patients during ACS.


METHODS
Whole blood and plasma samples from 32 patients with non-ST segment elevation myocardial infarction (NSTEMI) were collected after administration of clopidogrel. Whole blood and plasma fibrin clot strength (MA) were determined by TEG. Platelet aggregation was determined by light transmittance aggregometry (LTA) using adenosine 5'-diphosphate (ADP), thrombin receptor activation peptide (TRAP), or collagen as agonists. Fibrinogen and C-reactive protein (CRP) concentrations were measured by ELISA.


RESULTS
Heightened plasma fibrin clot strength was associated with increased platelet reactivity stimulated by ADP (ρ=0.536; p=0.002), TRAP (ρ=0.481; p=0.007), and collagen (ρ=0.538; p=0.01). In contrast to plasma fibrin MA, whole blood MA did not correlate with platelet aggregation. Platelet count was the primary contributor to the difference in thrombin induced whole blood MA and plasma fibrin MA. Increasing levels of CRP were associated with increased plasma fibrin clot strength and platelet reactivity.


CONCLUSIONS
Our data suggest that inflammation is associated with increased plasma fibrin clot strength and lower platelet inhibition by clopidogrel during ACS. Platelet count is a main contributor to additional contractile force of whole blood TEG as compared to plasma TEG during treatment with clopidogrel.
Division of Clinical Pharmacology, Indiana University School of Medicine, Indianapolis, IN 46202, USA.
Deshun
D
Lu
Janelle
J
Owens
Rolf P
RP
Kreutz
D054058:Acute Coronary Syndrome / Q000097:blood* / Q000188:drug therapy* / Q000473:pathology; D002097:C-Reactive Protein / Q000378:metabolism; D000077144:Clopidogrel; D005260:Female; D005340:Fibrinogen / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010974:Platelet Aggregation / Q000187:drug effects; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use*; D010979:Platelet Function Tests; D013916:Thrombelastography / Q000379:methods; D013988:Ticlopidine / Q000031:analogs & derivatives* / Q000627:therapeutic use
D010975:Platelet Aggregation Inhibitors; D005340:Fibrinogen; D002097:C-Reactive Protein; D000077144:Clopidogrel; D013988:Ticlopidine
ACS; ADP; C-reactive protein; CRP; Clopidogrel; Coagulation; G; K; LTA; MA; NSTEMI; PPP; PRP; Platelet; R; TRAP; Thrombelastography; acute coronary syndrome; adenosine 5’-diphosphate; angle constant; clot formation time; diff; difference; light transmittance aggregometry; maximum amplitude; maximum clot strength; non-ST segment elevation myocardial infarction; platelet poor plasma; platelet rich plasma; thrombin receptor activation peptide; time to fibrin formation; α