ticagrelor and Blood-Coagulation-Disorders

Acute ischemic stroke (AIS) due to cerebral artery occlusion is often treated by thrombolytics or antithrombotic drugs. Thromboelastography (TEG) is a noninvasive test that provides a dynamic overview of the coagulation process. TEG may help guide thrombolytic and antithrombotic therapy in AIS. This article aims to highlight the potential use of TEG in AIS patients by reviewing available studies. We conducted a literature review, including PubMed and Cochrane library databases. The following keywords were used to find relevant studies: thromboelastography, TEG, acute ischemic stroke, stroke, coagulopathy, antiplatelet, and anticoagulant treatment. We identified 142 papers and after abstract review, we included 24 studies in this report. TEG identified a hypercoagulable state in AIS patients represented by short R, K, and greater α: angle in all papers included. Modification of TEG parameters induced by intravenous thrombolysis was inconsistent but prolonged lysis (increased LY30) and weaker clots (lower maximum amplitude) were most frequent. TEG detected hypo-coagulopathy induced by dual antiplatelet therapy as well as antiplatelet drug resistance, with ticagrelor and aspirin having greater inhibition of platelet activity. A prolonged R-value seems to be the most reliable TEG parameter in detecting the anticoagulant effect of factor Xa inhibitor treatment. TEG might represent a useful point-of-care test for emergency decision-making in AIS patients and a tool for individualized treatment options. This hypothesis needs validation in a large cohort of prospectively studied AIS patients.

Topics: Aspirin; Blood Coagulation Disorders; Factor Xa Inhibitors; Fibrinolytic Agents; Humans; Ischemic Stroke; Platelet Aggregation Inhibitors; Thrombelastography; Ticagrelor

A therapeutic window in antiplatelet treatment has been associated with concurrent lowering of bleeding and ischemic risks. Prasugrel and ticagrelor provide potent platelet inhibition, but may increase bleeding. No study has evaluated a personalized therapy with selective use of novel P2Y12 inhibitory agents compared to empiric ticagrelor use. The objective of this study was to compare a personalized anti-platelet therapy strategy to empiric ticagrelor in achieving a therapeutic window.. Using the CAPITAL registry, we performed a retrospective analysis to evaluate a personalized anti-platelet therapy (PAT) strategy, using a pharmacogenetic approach, and compared it to empiric ticagrelor. In the PAT group, carriers of CYP2C19*2 received prasugrel and non-carriers received clopidogrel. The primary outcome was the proportion of patients within a validated therapeutic window, after a steady state treatment (≥48h) of antiplatelet therapy, as measured by a P2Y12 reaction unit (PRU) >85 and <208.. Of 199 patients with platelet function measurements, 150 received PAT, while 49 received ticagrelor. Significantly more patients on PAT achieved the primary outcome (50.0% vs. 4.1%, p<0.0001). This was predominantly driven by an increase in low on-treatment reactivity with ticagrelor (95.9% vs. 37.3%, p<0.0001). Multivariable analysis demonstrated PAT to be the strongest predictor of achieving PRU values within the therapeutic window (odds ratio 20.27; 95% CI: 4.33-94.82, p=0.0001).. Patients treated with PAT were more likely to achieve a therapeutic window compared to a strategy of ticagrelor. Future prospective evaluation of novel PAT strategies will be required to prove clinical utility.

Topics: Adenosine; Adult; Aged; Blood Coagulation Disorders; Blood Platelets; Female; Humans; Male; Middle Aged; Pharmacogenetics; Platelet Aggregation Inhibitors; Platelet Function Tests; Precision Medicine; Purinergic P2Y Receptor Antagonists; Registries; Retrospective Studies; Ticagrelor; Treatment Outcome