Platelet Inhibition and Anticoagulation in Endovascular Neurosurgery

SummaryAfter incubation of platelet-rich plasma with labelled adenosine or ADP, platelet incorporation of radioactivity was assessed. Platelets were rapidly separated for counting by filtration through cellulose acetate Millipore. Inulin-H3 served as a plasma marker, and triple isotope techniques permitted simultaneous assessment of the behavior of the adenine and phosphate moieties of ADP without washing of platelets. In other experiments, electron microscopic radioautography was employed to trace the label after platelet incorporation.The results were consistent with previous reports that ADP is dephosphorylated in plasma and is incorporated by platelets only as a dephosphorylated residue, probably adenosine. The label crossed the platelet membrane and entered the platelet, where it was distributed in platelet granules and the agranular cell sap. Concentration within granules occurred to a minor degree.The results support the hypothesis that platelet aggregation by ADP occurs without a persistent bond of ADP to the platelet. Inhibition of aggregation by adenosine probably depends on a metabolic or transport process rather than on competition between adenosine and ADP for platelet binding sites.

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Combined Thrombin and Platelet Inhibition Treatment for HIT Patients

Hämostaseologie ◽

10.1055/s-0038-1660400 ◽

1999 ◽

Vol 19 (03) ◽

pp. 128-133 ◽

Cited By ~ 1

Author(s):

B.E. Lewis ◽

W. P. Jeske ◽

F. Leya ◽

Diane Wallis ◽

M. Bakhos ◽

...

Keyword(s):

Standard Dose ◽

Combined Therapy ◽

Platelet Inhibition ◽

Thrombin Inhibitors ◽

Thrombin Inhibitor ◽

Heparin Induced Thrombocytopenia ◽

Acute Thrombosis ◽

Anti Platelet Drug ◽

Receptor Inhibitor

SummaryDespite the use of potent anticoagulants such as r-hirudin and argatroban, the morbidity and mortality in heparin-induced thrombocytopenia (HIT) patients remains unacceptable. Data from our in vitro investigations show that thrombin inhibitors do not block platelet activation induced by heparin antibodies and heparin but that GPIIb/IIIa receptor inhibitors do block this process. We have treated four HIT positive patients with a combined therapy of thrombin inhibitor and GPIIb/IIIa receptor inhibitor when treatment with thrombin inhibitor alone failed to alleviate acute thrombosis. Combination therapies included r-hirudin (Refludan®) with tirofiban (Aggrastat®) and argatroban (Novastan®) with abciximab (ReoPro®). A reduced dose of the thrombin inhibitor was used with the standard dose of the anti-platelet drug. In all cases, there was no overt bleeding which required intervention, and all patients exhibited clinical improvement or full recovery. These case studies suggest that treatment of active thrombosis in HIT patients with adjunct GPIIb/IIIa receptor inhibitor therapy may be more effective than thrombin inhibitor treatment alone.

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Hybrid Coronary Revascularization: An Overview of Options for Anticoagulation and Platelet Inhibition

The Heart Surgery Forum ◽

10.1532/hsf98.20101157 ◽

2010 ◽

Vol 13 (6) ◽

pp. E405-E408 ◽

Cited By ~ 2

Author(s):

David Zimrin ◽

Johannes Bonatti ◽

Mark R. Vesely ◽

Eric J. Lehr

Keyword(s):

Coronary Revascularization ◽

Platelet Inhibition ◽

Hybrid Coronary Revascularization

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High-Dose Clopidogrel Loading in Percutaneous Coronary Intervention

Annals of Pharmacotherapy ◽

10.1345/aph.1e463 ◽

2005 ◽

Vol 39 (5) ◽

pp. 918-922 ◽

Cited By ~ 5

Author(s):

Kristen L Longstreth ◽

James R Wertz

Keyword(s):

Percutaneous Coronary Intervention ◽

Coronary Intervention ◽

Drug Manufacturer ◽

Platelet Inhibition ◽

High Dose ◽

Loading Dose ◽

Percutaneous Coronary ◽

Safety Studies ◽

Risk Patients ◽

Time Required

OBJECTIVE: To review the use of a 600-mg clopidogrel loading dose in patients undergoing percutaneous coronary intervention (PCI). DATA SOURCES: Human clinical trials and platelet studies available through PubMed (1966–March 2005), bibliographies of pertinent articles, and citations supplied by the drug manufacturer were accessed. DATA SYNTHESIS: The administration of a 600-mg loading dose of clopidogrel can decrease the time required for maximum platelet inhibition to 2 hours compared with ⩾6 hours achieved with 300 mg. This higher loading dose has been investigated in multiple platelet studies and one observational report. Several randomized controlled trials have used a 600-mg loading dose; however, these studies were not designed to evaluate the efficacy and safety of this loading regimen. To date, only one randomized trial has compared the 600-mg loading dose with a 300-mg loading dose. CONCLUSIONS: When compared with a conventional loading regimen of 300 mg in lower-risk patients, pretreatment with clopidogrel 600 mg was shown to be more effective in reducing periprocedural events and demonstrated similar safety. Studies are needed to clarify the use of a 600-mg loading dose in higher-risk patients, with concomitant glycoprotein IIb/IIIa receptor antagonism, or when administration is delayed until immediately before or after PCI.

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Pleiotropic Effects of Acetylsalicylic Acid after Coronary Artery Bypass Grafting—Beyond Platelet Inhibition

Journal of Clinical Medicine ◽

10.3390/jcm10112317 ◽

2021 ◽

Vol 10 (11) ◽

pp. 2317

Author(s):

Dominika Siwik ◽

Magdalena Gajewska ◽

Katarzyna Karoń ◽

Kinga Pluta ◽

Mateusz Wondołkowski ◽

...

Keyword(s):

Coronary Artery ◽

Coronary Artery Bypass Grafting ◽

Acetylsalicylic Acid ◽

Coronary Artery Bypass ◽

Artery Bypass ◽

Platelet Inhibition ◽

Pleiotropic Effects ◽

Bypass Grafting ◽

Graft Occlusion ◽

Artery Bypass Grafting

Acetylsalicylic acid (ASA) is one of the most frequently used medications worldwide. Yet, the main indications for ASA are the atherosclerosis-based cardiovascular diseases, including coronary artery disease (CAD). Despite the increasing number of percutaneous procedures to treat CAD, coronary artery bypass grafting (CABG) remains the treatment of choice in patients with multivessel CAD and intermediate or high anatomical lesion complexity. Taking into account that CABG is a potent activator of inflammation, ASA is an important part in the postoperative therapy, not only due to ASA antiplatelet action, but also as an anti-inflammatory agent. Additional benefits of ASA after CABG include anticancerogenic, hypotensive, antiproliferative, anti-osteoporotic, and neuroprotective effects, which are especially important in patients after CABG, prone to hypertension, graft occlusion, atherosclerosis progression, and cognitive impairment. Here, we discuss the pleiotropic effects of ASA after CABG and provide insights into the mechanisms underlying the benefits of treatment with ASA, beyond platelet inhibition. Since some of ASA pleiotropic effects seem to increase the risk of bleeding, it could be considered a starting point to investigate whether the increase of the intensity of the treatment with ASA after CABG is beneficial for the CABG group of patients.

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P2Y12 inhibitors in neuroendovascular surgery: An opportunity for precision medicine

Interventional Neuroradiology ◽

10.1177/1591019921991394 ◽

2021 ◽

pp. 159101992199139

Author(s):

Axel Rosengart ◽

Malie K Collins ◽

Philipp Hendrix ◽

Ryley Uber ◽

Melissa Sartori ◽

...

Keyword(s):

Adverse Events ◽

Precision Medicine ◽

Point Of Care ◽

Indirect Evidence ◽

Cost Benefit ◽

Interventional Cardiology ◽

Platelet Inhibition ◽

Response Monitoring ◽

P2y12 Inhibitor ◽

P2y12 Inhibitors

Introduction Dual antiplatelet therapy (DAPT), primarily the combination of aspirin with a P2Y12 inhibitor, in patients undergoing intravascular stent or flow diverter placement remains the primary strategy to reduce device-related thromboembolic complications. However, selection, timing, and dosing of DAPT is critical and can be challenging given the existing significant inter- and intraindividual response variations to P2Y12 inhibitors. Methods Assessment of indexed, peer-reviewed literature from 2000 to 2020 in interventional cardiology and neuroendovascular therapeutics with critical, peer-reviewed appraisal and extraction of evidence and strategies to utilize DAPT in cardio- and neurovascular patients with endoluminal devices. Results Both geno- and phenotyping for DAPT are rapidly and conveniently available as point-of-care testing at a favorable cost-benefit ratio. Furthermore, systematic inclusion of a quantifying clinical risk score combined with an operator-linked, technical risk assessment for potential adverse events allows a more precise and individualized approach to new P2Y12 inhibitor therapy. Conclusions The latest evidence, primarily obtained from cardiovascular intervention trials, supports that combining patient pharmacogenetics with drug response monitoring, as part of an individually tailored, precision medicine approach, is both predictive and cost-effective in achieving and maintaining individual target platelet inhibition levels. Indirect evidence supports that this gain in optimizing drug responses translates to reducing main adverse events and overall treatment costs in patients undergoing DAPT after intracranial stent or flow diverting treatment.

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Use of Thromboelastography Platelet Mapping for Assessment of Individual Platelet Response Secondary to Oral Antiplatelet Therapy after Percutaneous Coronary Intervention: An Attempt to Start Personalized Antiplatelet Therapy in India

Journal of Cardiac Critical Care TSS ◽

10.1055/s-0041-1724225 ◽

2021 ◽

Author(s):

Suvro Sankha Datta ◽

Dibyendu De ◽

Nadeem Afroz Muslim

Keyword(s):

Percutaneous Coronary Intervention ◽

Antiplatelet Therapy ◽

Platelet Reactivity ◽

Coronary Intervention ◽

Platelet Inhibition ◽

P Value ◽

Platelet Response ◽

Percutaneous Coronary ◽

The Individual ◽

Platelet Functions

AbstractHigh on-treatment platelet reactivity (HPR) with P2Y12 receptor antagonists in patients treated with dual antiplatelet therapy (DAPT) is strongly associated with adverse ischemic events after percutaneous coronary intervention (PCI). This prospective study was conducted to assess individual platelet response and HPR to antiplatelet medications in post-PCI cases by thromboelastography platelet mapping (TEG-PM). Total 82 patients who were on aspirin and on either clopidogrel, prasugrel, or ticagrelor were evaluated. The percentage of platelet inhibition to arachidonic acid (AA) and adenosine disdiphosphate (ADP) was calculated by [100-{(MA ADP/AA–MA Fibrin) / (MA Thrombin–MA Fibrin) × 100}], taking 50% response as cut-off for HPR. HPR to clopidogrel and prasugrel was 14.29 and 12.5%, respectively. No HPR was detected to aspirin and ticagrelor. The mean percentage of platelet inhibition was significantly higher in patients with ticagrelor 82.99, 95% confidence interval (CI) of [77.3, 88.7] as compared with clopidogrel 72.21, 95% CI of [65.3, 79.1] and prasugrel 64.2, 95% CI of [52.5, 75.9] (p-value of 0.041 and 0.003, respectively). Aspirin along with ticagrelor is associated with a higher mean percentage of platelet inhibition, and lower HPR as compared with the usage of aspirin combined with clopidogrel or prasugrel. Additionally, it might also be concluded that TEG-PM could be used effectively to measure the individual platelet functions which would make oral antiplatelet therapy more personalized for cardiac patients.

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