ABSTRACT
BACKGROUND: Despite Antiplatelet therapy (APT), cardiovascular patients undergoing revascularisation remain at high risk for thrombotic events. Individual response to APT varies substantially, resulting in insufficient protection from thrombotic events due to high on-treatment platelet reactivity (HTPR) in ≤40% of patients. Individual variation in platelet response impairs APT guidance on a single patient level. Unfortunately, little is known about individual platelet response to APT over time, timing for accurate residual platelet reactivity measurement, or the optimal test to monitor residual platelet reactivity. AIMS: To investigate residual platelet reactivity variability over time in individual patients undergoing carotid endarterectomy (CEA) treated with clopidogrel. METHODS: Platelet reactivity was determined in patients undergoing CEA in a prospective, single-centre, observational study using the VerifyNow (change in turbidity from ADP-induced binding to fibrinogen-coated beads), the VASP assay (quantification of phosphorylation of vasodilator-stimulated phosphoprotein), and a flow-cytometry-based assay (PACT) at four perioperative time points. Genotyping identified slow (CYP2C19*2 and CYP2C19*3) and fast (CYP2C19*17) metabolisers. RESULTS: Between December 2017 and November 2019, 50 patients undergoing CEA were included. Platelet reactivity measured with the VerifyNow (p = < .001) and VASP (p = .029) changed over time, while the PACT did not. The VerifyNow identified patients changing HTRP status after surgery. The VASP identified patients changing HTPR status after eight weeks (p = .018). CYP2C19 genotyping identified 13 slow metabolisers. CONCLUSION: In patients undergoing CEA, perioperative platelet reactivity measurements fluctuate over time with little agreement between platelet reactivity assays. Consequently, HTPR status of individual patients measured with the VerifyNow and VASP assay changed over time. Therefore, generally used perioperative platelet reactivity measurements seem unreliable for adjusting perioperative APT strategy.
Subject(s)
Blood Platelets , Clopidogrel , Endarterectomy, Carotid , Platelet Aggregation Inhibitors , Humans , Male , Female , Aged , Pilot Projects , Blood Platelets/metabolism , Prospective Studies , Platelet Aggregation Inhibitors/therapeutic use , Platelet Aggregation Inhibitors/pharmacology , Clopidogrel/therapeutic use , Platelet Function Tests/methods , Middle Aged , Perioperative Period , Cytochrome P-450 CYP2C19/genetics , Cytochrome P-450 CYP2C19/metabolism , Vascular Surgical Procedures , Platelet Activation/drug effects , Aged, 80 and over , Cell Adhesion Molecules/metabolism , Cell Adhesion Molecules/blood , Microfilament Proteins/metabolism , Microfilament Proteins/genetics , Microfilament Proteins/bloodABSTRACT
Several studies have investigated aspects of cognitive functioning during late pregnancy or in the period around delivery. The present paper describes a controlled study of neurocognitive functioning in an early phase of pregnancy (14 weeks). Seventy-one pregnant women and 57 control subjects matched for age and education were tested with a cognitive test battery. Intentional learning was tested with the Verbal Learning Test, retrieval from semantic memory with the Fluency Test, and speed of information processing with the Concept Shifting Test, the Stroop test, and the Letter Digit Substitution Test. Results show that performance on tests measuring intentional learning and retrieval from semantic memory were lower in the pregnant group during early pregnancy as compared to a closely matched nonpregnant group. In contrast, speed of information processing was not different between the two groups. The differences observed in memory performance were not large and further research is needed to establish their clinical significance. In addition, the results should be interpreted with care, because our study has a cross-sectional design, which has limitations concerning the fact that preexisting performance differences might be possible. Therefore, longitudinal studies are essential to ascertain clear associations between pregnancy and cognitive performance.
