Thrombelastography Compared with Multiple Impedance Aggregometry to Assess High On-Clopidogrel Reactivity in Patients with Atrial Fibrillation Undergoing Percutaneous Coronary Intervention

Abstract

Background: High on-clopidogrel platelet reactivity (HPR) following percutaneous coronary intervention (PCI) is associated with increased ischemic risk. It is unclear whether conventional definitions of HPR apply to patients with concomitant oral anticoagulation (OAC). This study aimed to compare the performance of multiple platelet aggregometry (MEA) and thrombelastography (TEG) to detect HPR in patients with atrial fibrillation (AF) and indication for an OAC. Methods: In this observational single-center cohort study, MEA and TEG were performed in patients with AF with an indication for OAC on day 1 to 3 after PCI. The primary outcome was HPR as assessed by MEA (ADP area under the curve ≥ 46 units [U]) or TEG (MAADP ≥ 47 mm), respectively. The secondary exploratory outcomes were a composite of all-cause death, myocardial infarction (MI) or stroke and bleeding, as defined by the International Society on Thrombosis and Hemostasis, at 6 months. Results: Platelet function of 39 patients was analyzed. The median age was 78 (interquartile range [IQR] was 72−82) years. 25 (64%) patients were male, and 19 (49%) presented with acute coronary syndrome. All patients received acetylsalicylic acid and clopidogrel prior to PCI. Median (IQR) ADP-induced aggregation, MAADP, TRAP-induced aggregation, and MAthrombin were 9 (6−15) U, 50 (43−60) mm, 54 (35−77) U and 65 (60−67) mm, respectively. The rate of HPR was significantly higher if assessed by TEG compared with MEA (25 [64%] vs. 1 [3%]; p < 0.001). Within 6 months, four (10%) deaths, one (3%) MI and nine (23%) bleeding events occurred. Conclusion: In patients with AF undergoing PCI, the rates of HPR detected by TEG were significantly higher compared with MEA. Conventional cut-off values for HPR as proposed by consensus documents may need to be re-evaluated for this population at high ischemic and bleeding risk. Further studies are needed to assess the association with outcomes.

Keywords: atrial fibrillation; multiple electrode aggregometry; percutaneous coronary intervention; platelet reactivity; thrombelastography.

Figure 1

Platelet reactivity of patients with atrial fibrillation undergoing percutaneous intervention. (A) ADP- and (C) TRAP-induced aggregation as assessed by MEA and MA_ADP (B) and MA_Thrombin (D) as assessed by TEG. Median and interquartile range are represented by black lines. Red lines indicate conventional cut-off values (ADP AUC ≥ 46 U and MA_ADP ≥ 47 mm) or reference values suggested by the manufacturer (TRAP AUC 94-156 U, MA_Thrombin 53–68 mm), respectively.

Figure 2

Platelet reactivity according to oral anticoagulation. Aggregation values for ADP-induced aggregation as assessed by MEA (A) and MA_ADP as assessed by TEG (B) with and without OAC therapy. Red line represents HPR cut-off and black line median with interquartile range.

Figure 3

Correlation of multiple electrode aggregometry with thrombelastography. ADP AUC with MA_ADP (A) and TRAP AUC with MA_Thrombin (B).