Background
ACC/AHA guidelines advise waiting 5-7 days before operating on P2Y12 inhibitor-treated ACS patients, to allow dissipation of its antiplatelet effects. Platelet transfusion is often used to restore hemostasis during operations but its effectiveness and optimal timing are unclear. We investigated the degree of functional gains obtained from platelet-supplementation after loading and maintenance dual antiplatelet therapy [DAPT]with ticagrelor, and the influence of timing on this strategy.
Methods and Results
Following baseline platelet testing (Multiplate® Analyzer and VerifyNow®), CVD patients (n=20, 56.9±7.9 years, 65% male, 75% diabetic) received DAPT as a single loading-dose [LD: ticagrelor 180mg plus aspirin 325mg] and as daily/maintenance treatment for 5-7 days [MT: ticagrelor 90mg b.i.d. plus aspirin 81mg q.d.]. At 4-, 6-, 24- and 48-hours from (last) dosing, patients’ blood samples were supplemented with concentrated platelets from healthy donors in vitro, raising platelet counts by 0% (un-supplemented ‘control’), 25%, 50% and 75%, and the function retested. Reactivity in supplemented samples was compared with respective 0% sample and with the pre-treatment baseline. Results under LD and MT regimens were nearly identical. Platelet reactivity was higher (p<0.05) in nearly all supplemented samples vs. respective controls. Aggregations with supplementation were 59%-79% of baseline at 24-hours, and equal to baseline at 48-hours.
Conclusions
Platelet reactivity of ticagrelor-treated patients can be restored using concentrated platelets after a loading-dose/maintenance-therapy in a time-dependent manner under in vitro testing. Although statistically significant improvements are evident 6 hours after (last) dosing, up to 24 hours maybe needed for clinically meaningful restoration in platelet function.
Type-2 Diabetes Mellitus [T2DM] is associated with increased platelet reactivity and hypo-response to antiplatelet drugs. Ticagrelor, with its faster and more potent antiplatelet effects, was shown to reduce adverse events more than clopidogrel in the overall CAD patient population of PLATO trial, but the benefits did not reach statistical significance in the T2DM subgroup. To better understand these findings, we compared the antithrombotic effects of ticagrelor versus with clopidogrel in T2DM patients with cardiovascular disease. In a randomized, 2 treatment-sequence, crossover-design, T2DM patients (n=20, 57±8 years, 60 % male) received a loading-dose [LD] plus one week of daily-therapy [DT] of clopidogrel or ticagrelor. Treatment effects were assessed by measuring thrombus formation (Badimon Chamber) and platelet aggregation (Multiple Electrode Aggregometry (MEA) Analyzer and VerifyNow®) at 2- and 6-hour post-LD and on Day-7 of DT, in comparison with pre-treatment baseline. After 2 weeks of washout, patients switched to the second treatment under identical testing conditions. Ticagrelor significantly reduced thrombus formation versus baseline at 2- and 6-hour post-LD and Day-7 of DT (33 %, 40 % and 31 %, respectively, p<0.01 for all) whereas thrombus reductions with clopidogrel were much lower and significant only at 6-hour post-LD (16 %, 20 % and 17 %, respectively). Antithrombotic effect of ticagrelor at 6-hour was significantly stronger than clopidogrel (p<0.05). Platelet aggregation (MEA and VerifyNow®) was inhibited by both treatments but effects of ticagrelor were significantly stronger at each time-point. Ticagrelor exhibits a faster and more potent antithrombotic effect than clopidogrel in T2DM patients with cardiovascular disease, supporting its use in this population.
Management of tuberculosis (TB) has witnessed several changes over the past decades. While medical management is now the mainstay of therapy, surgical intervention was once the only treatment option physicians had to offer. We discuss some historical surgical procedures and take a quick glance at the evolution of TB therapy. We note the importance of adequate history-taking and the implications of what seemingly obsolete techniques may have in contemporary practice. We also highlight the re-emergence of surgical options in the modern era with the rise of multidrug-resistance.
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