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Published on: November 8, 2024
Impact of Timing on the Functional Recovery Achieved With Platelet Supplementation After Treatment With Ticagrelor
M Urooj Zafar1, Donald A Smith1, Usman Baber1
1From the Cardiovascular Institute, Icahn School of Medicine at Mount Sinai, New York, NY (M.U.Z., D.A.S., U.B., S.S., K.C., D.W.L., C.A.L.-K., J.R.-M., G.J.B., V.F., J.J.B.); and Department of Hematopathology, Hospital Clinic, Barcelona, Spain (G.E.).
Insights
Platelet transfusion can restore antiplatelet effects in ticagrelor-treated patients, with function returning to baseline levels within 48 hours. This finding may inform surgical timing for acute coronary syndrome patients on dual antiplatelet therapy.
Area of Science:
- Cardiology
- Hematology
- Pharmacology
Background:
- Current guidelines recommend a 5-7 day waiting period after P2Y12 inhibitor therapy for surgery in acute coronary syndrome (ACS) patients.
- Platelet transfusion is a common strategy to restore hemostasis, but its efficacy and optimal timing post-ticagrelor are not well-defined.
Purpose of the Study:
- To investigate the functional recovery of platelets after ticagrelor therapy with platelet supplementation.
- To determine the influence of timing on the effectiveness of platelet supplementation in restoring platelet function.
Main Methods:
- 20 cardiovascular disease patients received dual antiplatelet therapy (ticagrelor and aspirin).
- Blood samples were supplemented in vitro with concentrated platelets at varying percentages (0-75%) at 4, 6, 24, and 48 hours post-dosing.
- Platelet function was assessed using Multiplate Analyzer and VerifyNow assays.
Main Results:
- Platelet reactivity significantly improved (P<0.05) in supplemented samples compared to controls across various time points.
- Platelet aggregation reached 59-79% of baseline at 24 hours and returned to baseline levels by 48 hours post-dosing.
- Results were consistent for both loading and maintenance phases of ticagrelor therapy.
Conclusions:
- In vitro platelet supplementation can restore platelet function in ticagrelor-treated patients in a time-dependent manner.
- While significant improvements are seen by 6 hours, approximately 24 hours may be required for clinically meaningful platelet function restoration.
Background:
American College of Cardiology/American Heart Association guidelines advise waiting 5 to 7 days before operating on P2Y12 inhibitor-treated acute coronary syndrome 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 of dual antiplatelet therapy with ticagrelor and the influence of timing on this strategy.
Methods And Results:
After baseline platelet testing (Multiplate Analyzer and VerifyNow), cardiovascular disease patients (n=20; 56.9±7.9 years; 65% men; 75% diabetic) received dual antiplatelet therapy as a single loading dose (ticagrelor 180 mg plus aspirin 325 mg) and as daily/maintenance treatment for 5 to 7 days (maintenance therapy: ticagrelor 90 mg BID plus aspirin 81 mg QD). 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% (unsupplemented control), 25%, 50%, and 75%, and the function retested. Reactivity in supplemented samples was compared with respective 0% sample and with the pretreatment baseline. Results under loading dose and maintenance therapy regimens were nearly identical. Platelet reactivity was higher (P<0.05) in nearly all supplemented samples versus respective controls. Aggregations with supplementation were 59% to 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, ≥24 hours maybe needed for clinically meaningful restoration in platelet function.
Clinical Trial Registration:
URL: https://clinicaltrials.gov. Unique identifier: NCT02201394.
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