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.

Association of lipoprotein(a) with intrinsic and on-clopidogrel platelet reactivity.

Lipoprotein(a) [Lp(a)] is an independent, genetically determined, and causal risk factor for cardiovascular disease. Laboratory data have suggested an interaction of Lp(a) with platelet function, potentially caused by its interaction with platelet receptors. So far, the potential association of Lp(a) with platelet activation and reactivity has not been proven in larger clinical cohorts. This study analyzed intrinsic platelet reactivity before loading with clopidogrel 600 mg and on-treatment platelet reactivity tested 24 h following loading in patients undergoing elective coronary angiography. Platelet reactivity was tested by optical aggregometry following stimulation with collagen or adenosine diphosphate as well as by flow cytometry. Lp(a) levels were directly measured in all patients from fresh samples. The present analysis included 1912 patients. Lp(a) levels ranged between 0 and 332 mg/dl. There was a significant association of rising levels of Lp(a) with a higher prevalence of a history of ischemic heart disease (p < 0.001) and more extensive coronary artery disease (p = 0.001). Results for intrinsic (p = 0.80) and on-clopidogrel platelet reactivity (p = 0.81) did not differ between quartiles of Lp(a) levels. Flow cytometry analyses of expression of different platelet surface proteins (CD41, CD62P or PAC-1) confirmed these findings. Correlation analyses of levels of Lp(a) with any of the tested platelet activation markers did not show any correlation. The present data do not support the hypothesis of an interaction of Lp(a) with platelet reactivity.

Clinical and radiographical ten years long-term outcome of microfracture vs. autologous chondrocyte implantation: a matched-pair analysis.

PURPOSE: To compare the clinical and radiographical long-term outcome of microfracture (MFX) and first-generation periosteum-covered autologous chondrocyte implantation (ACI-P). METHODS: All subjects (n = 86) who had been treated with knee joint ACI-P or microfracture (n = 76) with a post-operative follow-up of at least ten years were selected. Clinical pre- and post-operative outcomes were analyzed by numeric analog scale (NAS) for pain, Lysholm, Tegner, IKDC, and KOOS score. Radiographical evaluation was visualized by magnetic resonance imaging (MRI). Assessment of the regenerate quality was performed by the magnetic resonance observation of cartilage repair tissue (MOCART) and modified knee osteoarthritis scoring system (mKOSS). Relaxation time (RT) of T2 maps enabled a microstructural cartilage analysis. RESULTS: MFX and ACI of 44 patients (24 females, 20 males; mean age 38.9 ± 12.1 years) resulted in a good long-term outcome with low pain scores and significant improved clinical scores. The final Lysholm and functional NAS scores were significantly higher in the MFX group (Lysholm: MFX 82 ± 15 vs. ACI-P 71 ± 18 p = 0.027; NAS function: MFX 8.1 ± 3.5 vs. ACI-P 6.0 ± 2.5; p = 0.003). The MOCART score did not show any qualitative differences. KOSS analysis demonstrated that cartilage repair of small defects resulted in a significant better outcome. T2-relaxation times were without difference between groups at the region of the regenerate tissue. CONCLUSION: This study did not demonstrate coherent statistical differences between both cartilage repair procedures. MFX might be superior in the treatment of small cartilage defects.

Impact of On-Clopidogrel Platelet Reactivity on Incidence of Peri-Interventional Bleeding in Patients Undergoing Transcatheter Aortic Valve Implantation.

Dual anti-platelet therapy (DAPT) with clopidogrel and acetylsalicylic acid (ASA) has previously been recommended after transcatheter aortic valve implantation (TAVI) and is still the standard of care in patients who underwent coronary stent placement within 3 months prior to TAVI. This study sought to evaluate whether on-treatment platelet reactivity is a predictor for the occurrence of bleeding events after TAVI. This study enrolled 484 patients undergoing TAVI from November 2013 until April 2018. Patients were either on long-term DAPT with clopidogrel and ASA or received loading doses of both drugs before TAVI, reflecting the standard of care at the time of the patient's enrollment. Platelet reactivity was determined by multi-electrode impedance aggregometry before TAVI, at days 1 and 5 thereafter. Peri-interventional bleeding was assessed up to 5 days following TAVI and coded according to BARC-classification. Bleeding events were seen in 199 (41.1%) patients. The most frequent were BARC 2 bleeding cases (24.2%), followed by BARC 1 (6.0%), BARC 3b (5.2%), and BARC 3a (4.5%) cases. Low on-clopidogrel platelet reactivity before TAVI was present in 243 patients, of which 44.4% had a bleeding event. In contrast, the incidence of bleeding was 30.5% in the 95 patients with high on-clopidogrel platelet reactivity. Multivariate logistic regression analysis identified low/normal/high on-clopidogrel platelet reactivity (OR: 0.533; CI: 0.309-0.917; p = 0.023) and use of oral anticoagulation (OR: 1.766; CI: 1.209-2.581; p = 0.003) as strongest predictors for peri-interventional bleeding events. These findings support current recommendations advocating against the routine use of dual antiplatelet therapy following TAVI.

Reticulated Platelets in Medicine: Current Evidence and Further Perspectives.

Reticulated platelets (RPs) are young thrombocytes, newly released from the bone marrow. The identification and quantification of these cells remained difficult for decades due to a lack of standardized preanalytical and analytical methods. With the introduction of automated hematology analyzers in clinical routine, the determination of RPs, either as a total count or as a fraction, became more reliable, faster and more affordable. Currently, RPs are the focus of research in multiple clinical settings. In cardiovascular medicine, recent studies have focused on the relationship between RPs, coronary artery disease (CAD) and clinical outcomes, as well as the impact of RPs on the effects of antiplatelet therapy. Cohort studies showed increased levels of RPs in patients with acute coronary syndrome (ACS) or cardioembolic stroke. In patients with ACS, increased levels of RPs were also associated with an increased incidence of major ischemic cardiovascular events during follow-up. Further studies showed an association of levels of RPs with the antiplatelet response to less-potent P2Y12 inhibitors. In patients with paroxysmal atrial fibrillation undergoing pulmonary vein isolation, levels of RPs differed significantly depending on the achieved rhythm (sinus rhythm vs. recurrent atrial fibrillation). Levels of RPs appear to also be predictive for bleeding events in patients with various hematological diagnoses. Although no causal relationship has so far been proven, RP values have been associated with a large number of pathologies and clinical scenarios. This review summarizes the current evidence with regard to RPs and their potential diagnostic and prognostic value for noncardiovascular patients and for cardiovascular patients in particular. It describes further perspectives on how the testing of these cells might improve the treatment of cardiovascular patients.