Monitoring of Aspirin (ASA) Pharmacodynamics with the Platelet Function Analyzer PFA-100®

Homoncik, Monika; Hergovich, Nicole; Stohlawetz, Petra; Panzer, Simon; Speiser, Wolfgang; Jilma, Bernd

doi:10.1055/s-0037-1613805

Cited by 184 publications

(144 citation statements)

References 22 publications

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“…At the individual level, increased CEPI-CT after aspirin intake correlates well with the basal CEPI-CT, indicating that subjects with low basal CEPI-CT may require higher aspirin doses to inhibit platelet plug formation (Homoncik et al, 2000). Our data suggest that inflammation-induced VWF release shortens CTs.…”

Section: Discussionmentioning

confidence: 54%

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Systemic inflammation increases shear stress‐induced platelet plug formation measured by the PFA‐100

et al. 2000

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Summary. The PFA-100 measures platelet plug formation under shear stress and is strongly dependent on von Willebrand Factor (VWF) levels in plasma. We therefore hypothesized that elevated VWF levels, possibly as a result of acute inflammation, adversely influence PFA-100 results. Healthy volunteers received either 2 ng/kg endotoxin or placebo in a randomized controlled trial. Four hours after endotoxin (but not placebo) infusion VWF levels increased by 85%, collagen epinephrine-induced closure time (CT) decreased by 47% and collagen ADP-CT decreased by 38% (P , 0´0001) respectively. In conclusion, systemic inflammation has a major impact on the results obtained by PFA-100 and may confound interpretation of platelet function.

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Section: Discussionmentioning

confidence: 54%

“…von Willebrand disease (VWD)]. It does so by measuring collagen-epinephrine (CEPI)-and collagen-ADP (CADP)-induced platelet plug formation under high shear stress conditions, and is strongly dependent on von Willebrand factor (VWF) levels in plasma (Fressinaud et al, 1999;Harrison et al, 1999;Homoncik et al, 2000).…”

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confidence: 99%

Systemic inflammation increases shear stress‐induced platelet plug formation measured by the PFA‐100

et al. 2000

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“…Further investigations revealed a day-to-day variability of 9 to 12% and a diurnal variation as well, with about 30% longer CEPI-CT values in the afternoon than in the morning [30][31][32].…”

Section: Discussionmentioning

confidence: 99%

Assessment of clopidogrel non-response by the PFA-100® system using the new test cartridge INNOVANCE® PFA P2Y

et al. 2010

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Until now, the PFA-100® system has been considered unsuitable for monitoring clopidogrel efficacy. The authors evaluated platelet function in PAOD (peripheral arterial occlusive disease) patients using a new PFA-100® test cartridge (product name: INNOVANCE® PFA P2Y*) specifically designed for this purpose. Twenty-two stable PAOD patients on antithrombotic therapy with clopidogrel alone (n = 22) and 18 patients undergoing a peripheral catheter intervention, preliminarily treated with 100 mg/d aspirin followed by co-administration of clopidogrel (loading dose 300 mg, maintenance dose 75/d), were enrolled in this study. Defining non-responsiveness to clopidogrel as an aggregation response within the reference range (90% central interval), four (18.2%) non-responders using LTA induced by 5 µM ADP and six (27.3%) non-responders using LTA induced by 2 µM ADP (LateAggr >72.1% and >42.9%, respectively) were identified. INNOVANCE® PFA P2Y* determined six (27.3%) non-responders (CT<87s). Agreement between the two aggregometry assays and INNOVANCE® PFA P2Y* on the definition of clopidogrel response and non-response exceeded 70%. Only three patients were uniformly identified as clopidogrel non-responders by all three assays. When clopidogrel was co-administered with aspirin, two (11.1%) non-responders to clopidogrel were detected with INNOVANCE® PFA P2Y*, whereas ADP-induced LTA found all patients to be responsive. INNOVANCE® PFA P2Y* appears to be suitable for monitoring the effect of clopidogrel on platelet function. Its sensitivity in detecting responsiveness or non-responsiveness to clopidogrel is comparable to ADP-induced LTA. Additional prospective studies are needed to clarify the clinical relevance of the test results and classification obtained with INNOVANCE® PFA P2Y*. Response to Reviewers: FFM, 08/11/2009Dear editor and reviewers, Thank you for your comments on our manuscript. We performed the changes that you asked us to do. The changes are highlighted in blue. You will find a point-by-point response in the following. We hope that we addressed your concerns satisfactorily and that our manuscript is now acceptable for publication. Yours sincerelyDr. Birgit Linnemann, M.D. Ad reviewer 1:Ad 1: The reasons why we used lower ADP concentration in LTA was added. In a previous work we have shown that late aggregation using 2 μM ADP in non-adjusted PRP provides a good discrimination between clopidogrel treated patients and healthy subjects. However, we were also able to show that in platelet count-adjusted PRP, higher concentrations were necessary to differentiate between patients on clopidogrel treatment and subjects without clopidogrel medication. See reference 22.Ad 2: We agree that the figures 1-3 are quite similar. So we decided to remove fig. 1 and 3 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 42 43 44 45 46 47 48 49 50 51 52 53 54 55 56 57 58 59 60 61 62 63 64 65 2 Abstra...

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“…The time taken to occlude the hole is the closure time (CT), a measure of overall platelet-related haemostasis and this interval will be prolonged depending on the platelet activity. The use of two different cartridges with distinct agonists allows to distinguish the platelet function alterations due to intrinsic defects (principally by using CADP cartridge) or to antiplatelet therapy with ASA (CEPI cartridge) [93][94][95][96][97] , whereas the new Innovance cartridge is affected by thienopyridine therapy [98] . In comparison to BT test, this method is revealed more sensitive [27,46] especially for diagnosis of VWD and platelet function defects [25] .…”

Section: Platelet Function Point-of-care Testingmentioning

confidence: 99%

Assessment of platelet function: Laboratory and point-of-care methods

Paniccia¹

2014

WJTM

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In the event of blood vessel damage, human platelets are promptly recruited on the site of injury and, after their adhesion, activation and aggregation, prevent blood loss with the formation of a clot. The consequence of abnormal regulation can be either hemorrhage or the development of thrombosis. Qualitative and/or quantitative defects in platelets promote bleeding, whereas the residual reactivity of platelets, despite antiplatelet therapies, play an important role in promoting arterial thrombotic complications. Platelet function is traditionally assessed to investigate the origin of a bleeding syndrome, to predict the risk of bleeding prior surgery or during pregnancy or to monitor the efficacy of antiplatelet therapy in thrombotic syndromes that, now, can be considered a new discipline. "Old" platelet function laboratory tests such as the evaluation of bleeding time and the platelet aggregation analysis in platelet-rich plasma are traditionally utilized to aid in the diagnosis and management of patients with platelet and hemostatic disorders and used as diagnostic tools both in bleeding and thrombotic diathesis in specialized laboratories. Now, new and renewed automated systems have been introduced to provide a simple, rapid assessment of platelet function including point of care methods. These new methodologies are also suitable for being used in non-specialized laboratories and in critical area for assessing platelet function in whole blood without the requirement of sample processing. Some of these methods are also beginning to be incorporated into routine clinical use and can be utilized as not only as first panel for the diagnosis of platelet dysfunction, but also for monitoring anti-platelet therapy and to potentially assess risk of both bleeding and/or thrombosis.© 2014 Baishideng Publishing Group Inc. All rights reserved.Key words: Platelets; Method; Test; Point of care testing; Laboratory assessment; Bleeding; Thrombosis; Platelet function Core tip: This review discussed the scenario of available platelet function laboratory and point-of-care methods suitable in different clinical setting. As this matter has become of crucial importance in the bleeding management and for monitoring antiplatelet therapies, improved ability to assess platelet function in a timely and efficient manner is essential. Traditional platelet function methods, requiring a fair degree of expertise, have been limited to specialized laboratory. Many efforts have been carried out for improving platelet function assays for centralized laboratory, such as different point-of-care testing methodologies have been developed. Moreover, different guidelines and recommendations for their method standardization are growing.

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Monitoring of Aspirin (ASA) Pharmacodynamics with the Platelet Function Analyzer PFA-100®

Cited by 184 publications

References 22 publications

Systemic inflammation increases shear stress‐induced platelet plug formation measured by the PFA‐100

Systemic inflammation increases shear stress‐induced platelet plug formation measured by the PFA‐100

Assessment of clopidogrel non-response by the PFA-100® system using the new test cartridge INNOVANCE® PFA P2Y

Assessment of platelet function: Laboratory and point-of-care methods

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