Platelet Function Measurement–Based Strategy to Reduce Bleeding and Waiting Time in Clopidogrel-Treated Patients Undergoing Coronary Artery Bypass Graft Surgery

Abstract

Background Our understanding of the natural history of idiopathic Parkinson's disease (PD) remains limited. In the era of potential disease modifying therapies, there is an urgent need for studies assessing the natural evolution of treated PD from onset so that relevant outcome measures can be identified for clinical trials. No previous studies have charted progression in unselected patients followed from the point of diagnosis. Methods A representative cohort of 132 PD patients was followed from diagnosis for up to 7.9 years (mean 5.2 years). Comprehensive clinical and neuropsychological evaluations were performed every 18 months. Disease progression was evaluated using well validated clinical measures (motor progression and development of dyskinesia on the Unified PD Rating Scale and HoehneYahr scale, dementia onset according to DSM-IV criteria). Multi-level linear modelling was used to chart the nature and rate of progression in parkinsonian symptoms and signs over time. The prognostic importance of baseline demogr'aphic, clinical and genetic variables was evaluated using survival analysis.Results Axial (gait and postural) symptoms evolve more rapidly than other motor features of PD and appear to be the best index of disease progression. Conversely, conventional outcome measures are relatively insensitive to change over time. Earlier onset of postural instability (HoehneYahr stage 3) is strongly associated with increased age at disease onset and has a significant impact on quality of life. Conclusions Dementia risk is associated with increased age, impaired baseline semantic fluency and the MAPT H1/H1 genotype. The efficacy of disease modifying therapies may be more meaningfully assessed in terms of their effects in delaying the major milestones of PD, such as postural instability and dementia, since it is these that have the greatest impact on patients.

Management of Antiplatelet Therapy in Patients With Coronary Artery Disease Requiring Cardiac and Noncardiac Surgery

“…119,120 In the The Timing Based on Platelet Function Strategy to Reduce Clopidogrel-Associated Bleeding Related to CABG (TARGET-CABG) study, 180 patients on aspirin with or without clopidogrel therapy underwent thromboelastography before planned on-pump CABG to assess clopidogrel responsiveness and guide the timing of surgery. 121 This strategy resulted in an overall 46% shortening of the guideline-recommended waiting period for clopidogreltreated patients and was associated with the same amount of bleeding observed in clopidogrel-naïve patients. The US Society of Thoracic Surgeons has recently recognized the high negative predictive value of preoperative point-of-care testing in identifying patients with residual platelet reactivity and assigned specific classes of recommendation for platelet function testing as a tool for assessing bleeding risk, limiting blood transfusion, and optimizing antiplatelet therapy of patients undergoing cardiac surgery 122 (Table 3).…”

How I use laboratory monitoring of antiplatelet therapy

“…on May 10, 2018. by guest www.bloodjournal.org From obligated to wait the requisite number of days listed in the drug labeling or guidelines. [80][81][82] CYP2C19*2 single nucleotide polymorphism. Clopidogrel is metabolized through the cytochrome P-450 family of enzymes to generate the active metabolite required for inhibition of the platelet ADP receptor P2Y 12 .…”

2014 ESC/ESA Guidelines on Non-cardiac Surgery: Cardiovascular Assessment and Management

“…74 In contrast, other guidelines recommend using platelet function tests for optimal timing of surgery, as discussed in a recent publication. 134,135 However, the guidelines do not provide the 'ideal' platelet function assay or a 'bleeding cut-off', and more research in this area is needed.…”