D-dimer and fibrinogen indicate ischemic risk in patients with atrial fibrillation after percutaneous coronary intervention.

BACKGROUND: This study aimed to evaluate the association of antiphospholipid antibodies (aPL) and conventional markers of coagulation with ischemic and bleeding risk in patients with atrial fibrillation (AF) undergoing percutaneous coronary intervention (PCI). METHODS: In this prospective two-center observational cohort study, patients with AF and an indication for oral anticoagulation (OAC) were enrolled after PCI. Blood was drawn on day 1-3 after PCI. Dilute Russell's viper venom time was used to determine lupus anticoagulant (LA) in OAC-free plasma. Anti-cardiolipin (aCL) IgG, IgM, and anti-ß2-Glycoprotein 1 (aß2GP1) IgG were analyzed by enzyme-linked immunosorbent assay (ELISA). Fibrinogen (FIB), d-dimer, and prothrombin fragment 1 and 2 (PF 1 + 2) were measured in citrated plasma. The primary ischemic outcome was time to major adverse cardiovascular events (MACE; death, myocardial infarction, or stroke) assessed at 6 months. Bleeding was defined according to International Society on Thrombosis and Haemostasis. RESULTS: 158 patients were enrolled between May 2020 and May 2021 on day 1-3 after PCI. The median age was 78 years (interquartile range [IQR] 72-82), 111 (70%) were male, and 39 (25%) presented with acute coronary syndrome. D-dimer was elevated in 74 (47%) patients, FIB was increased in 40 (25%) and PF1 + 2 in 68 (43%) patients. 32 (20%) patients had ≥ 1 antiphospholipid antibody elevated (aPL; LA: 19 [12%], aCL: 14 [9%], aß2GP1: 2 [1%]). The presence of aPL was neither significantly associated with MACE (HR 1.46, 95% CI [0.39-5.49], p = 0.579), nor bleeding (HR 1.07 [0.30-3.84], p = 0.917). Elevated d-dimer was significantly associated with higher risk for MACE (HR 5.06 [1.09-23.41], p = 0.038) and major bleeding (HR 7.04 [1.58-31.47], p = 0.011). Elevated D-dimer increased the predictive capacity of HAS-BLED for major bleedings (HAS-BLED: AUC 0.71 [0.60-0.83] vs. HAS-BLED + d-dimer: AUC 0.79 [0.70-0.88]; p = 0.025). Increased levels of FIB were associated with higher risk for MACE (HR 3.65 [1.11-11.96], p = 0.033). CONCLUSION: Biomarkers of coagulation might be suitable to assess ischemic and bleeding risk in patients with AF following PCI.

Low on-clopidogrel ADP- and TRAP-6-induced platelet aggregation in patients with atrial fibrillation undergoing percutaneous coronary intervention: an observational pilot study.

High on-clopidogrel platelet reactivity (HPR) associates with ischemic risk in patients after percutaneous intervention (PCI). This study aimed to evaluate the association of HPR as assessed by multiple electrode aggregometry (MEA) with ischemic, thromboembolic, and bleeding risk in patients with atrial fibrillation (AF) undergoing PCI. Patients with AF and an indication for oral anticoagulation (OAC) were included in this prospective cohort study on day 1-3 after PCI. Platelet aggregation [U] was analyzed by MEA. HPR and low platelet reactivity (LPR) were defined as ADP-induced aggregation ≥ 46 U and ≤ 18 U, respectively. TRAP-6-induced aggregation reference was 94-156 U. The primary outcome was time to all-cause death, myocardial infarction, or stroke at 6 months. The secondary outcome was time to non-major clinically relevant bleedings or major bleedings. 159 patients were enrolled between May 2020 and May 2021. The median age was 78 years (interquartile range 72-82) and 111 (70%) were male. Median ADP- and TRAP-induced aggregation were 12 (6-17) and 49 (35-68) U, respectively. 147 (93%) patients had a low overall aggregability. HPR was detected in 2 patients (1%) and 125 (79%) had LPR. ADP-induced aggregation did not significantly associate with the primary outcome (r = 0.081, p = 0.309) but correlated inversely with bleeding risk (r = - 0.201, p = 0.011). HPR status as assessed by MEA among patients with AF after PCI was rare and overall aggregability was low. Conventional cut-off values for HPR might be inappropriate for these patients. ADP-induced aggregation might be helpful to identify patients at risk for bleeding.

Time from blood draw to multiple electrode aggregometry and association with platelet reactivity.

Results from multiple electrode aggregometry (MEA) may vary according to pre-analytic factors. This study aimed to analyze the association of time from blood draw to MEA in patients undergoing percutaneous coronary intervention (PCI). In this observational single-center cohort study, platelet aggregation (aggregation units, U) was quantified by MEA (Multiplate Analyzer) after stimulation with adenosine diphosphate (ADP; final concentration [Fc] 6.4 µM), thrombin receptor activating peptide (TRAP; Fc 32 µM), or arachidonic acid (AA; Fc 0.5 mM) in patients treated with ASA and clopidogrel following PCI. High on-clopidogrel platelet reactivity (HPR) was defined as ADP-induced platelet aggregation ≥ 46 U. The manufacturer recommends performing the analysis within 30-180 min after blood draw. Patients were grouped according to the time from blood draw to MEA: 30-180 min, < 30 min, or > 180 min. Platelet function of 273 patients with coronary artery disease undergoing PCI with dual antiplatelet therapy was analyzed. The median age was 72 years (interquartile range, IQR 62-79) and 179 (66%) were male. Median ADP-, TRAP-, and AA-induced aggregation was 25 (IQR 18-36) U, 79 (IQR 63-96) U, and 12 (IQR 7-18) U, respectively. For those analyzed within 30-180 min from blood draw, no significant correlation of time from blood draw to MEA was observed 1) ADP (r = - 0.04, p = 0.51); 2) TRAP (r = - 0.06, p = 0.32); 3) AA (r = - 0.03, p = 0.67). In patients undergoing percutaneous coronary intervention and treated with dual antiplatelet therapy, the time from blood draw to multiple electrode aggregometry does not correlate with ADP- induced aggregation when the measurement occurred within the recommended time interval of 30-180 min after blood draw.

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

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.