Plasma and Whole Blood Clot Strength Measured by Thrombelastography in Patients Treated with Clopidogrel during Acute Coronary Syndromes

Abstract

Introduction 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. Materials and Methods Whole blood and plasma samples from 32 patients with nonST 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 main contributor to additional contractile force of whole blood TEG as compared to plasma TEG during treatment with clopidogrel.

Platelet factor XIIIa release during platelet aggregation and plasma clot strength measured by thrombelastography in patients with coronary artery disease treated with clopidogrel

“…Thus, variability in platelet derived FXIIIa may contribute to differences in prothrombotic phenotypes and risk of recurrent ischemic events. We have previously shown that thrombin induced whole blood TEG-G is predominantly influenced by platelet count, whereas plasma fibrin TEG-G is higher in clopidogrel responders as compared to non-responders [21]. Plasma TEG-G in our study correlated weakly with platelet count, similar to the extent previously published [21].…”

“…We have previously shown that thrombin induced whole blood TEG-G is predominantly influenced by platelet count, whereas plasma fibrin TEG-G is higher in clopidogrel responders as compared to non-responders [21]. Plasma TEG-G in our study correlated weakly with platelet count, similar to the extent previously published [21]. We have previously demonstrated that increased c-reactive protein in patients with coronary artery disease is associated with increased plasma TEG-G [17].…”

Effects of non-vitamin K antagonist oral anticoagulants on fibrin clot and whole blood clot formation, integrity and thrombolysis in patients with atrial fibrillation

“…Nevertheless, our data point to marked differences in the extent to which selected TEG and MPA indices are influenced by warfarin and the NOACs, as are summarised in Table 5 . Some of these differences are likely to reflect whole blood versus fibrin clot formation, as it is established that platelets contribute to a fibrin clot [ 22 , 23 ], although our control group are taking at least 75 mg of aspirin daily, and this drug may also influence lysis by tPA [ 24 ]. Our data also point to marked differences between the effects of the NOACs, suggesting that dabigatran is a more effective agent than apixaban and in one respect, than rivaroxaban.…”

Clopidogrel‐associated genetic variants on inhibition of platelet activity and clinical outcome for acute coronary syndrome patients

“…The MA was classified into the thrombin‐induced maximum coagulation strength (MA thrombin ), the 20 μmol/L ADP‐induced maximum coagulation strength (MA ADP ) and the fibrin‐induced maximum coagulation strength (MA Fibrin ) according to different types of activators added to the blood sample. The ADP‐induced IPA for clopidogrel was calculated by the formula: ADP‐induced IPA (%) = (MA ADP − MA Fibrin )/(MA thrombin − MA Fibrin ) . According to a previous study, the relating IPA <30% induced by 20 μmol/L ADP was defined as clopidogrel high on‐treatment platelet reactivity (HPR) .…”

“…The ADP-induced IPA for clopidogrel was calculated by the formula: ADPinduced IPA (%) = (MA ADP − MA Fibrin )/(MA thrombin − MA Fibrin ). 19 According to a previous study, the relating IPA <30% induced by 20 μmol/L ADP was defined as clopidogrel high on-treatment platelet reactivity (HPR). 20 Aspirin resistance is defined as the occurrence of more than 50% platelet aggregation after stimulation by 1 mmol/L AA as measured by TEG after aspirin therapy.…”