Måling av blodplatehemning under behandling med clopidogrel: Sammenligning av klassisk ADP-stimulert lystransmisjonsaggregometri (Born) med ulike hurtigtestmetoder
Fast platelet function tests can identify weak clopidogrel responders, but data on variability over time in clopidogrel responsiveness in several clinical settings are lacking. We wanted to explore long term variability of Multiple Electrode Aggregometry (MEA) measurements and the agreement between MEA and Light Transmissions Aggregometry (LTA) in patients with non-ST elevation myocardial infarction (NSTEMI) treated with aspirin and clopidogrel.
Parallel MEA and LTA were performed at baseline and after six and 12 weeks in 31 patients treated with percutaneous coronary intervention after NSTEMI. Parallel testings in both arterial and venous blood were performed at baseline. MEA and LTA cut-off levels were applied to discriminate aggregation values suggesting presence or absence of high platelet reactivity (HPR).
Arterial and venous MEA and LTA aggregation were similar. Within-subject variability in both MEA and LTA aggregation throughout the study was moderate. Of 93 parallell MEA/LTA observations, 81 (87.1%) gave the same HPR classification. MEA vs. LTA agreement at baseline was slightly inferior to that obtained after 12 weeks.
MEA and LTA aggregation in arterial and venous blood seem similar. Within-subject variability over time was moderate, and the agreement between LTA and MEA was good, and stable in most patients.
Platelet inhibition induced by clopidogrel can probably be monitored safely and efficiently by using fast Multiple Electrode Aggregometry.
Platelet aggregometry in patients on clopidogrel and aspirin
The aim of the study is to explore aspects of residual platelet reactivity in patients with coronary heart disease treated with aspirin and clopidogrel.
Two papers have so far been published, and the third and final paper has recently been accepted for publication.
Previous studies seemed to indicate that some patients treated with aspirin were "resistant" to the drug and therefore at increased risk of thrombosis. In the first paper we report that - based in vitro testing with arachidonic acid stimulated light transmission aggregometry (LTA), no case of aspirin resistance (AR) was found among 270 patients with stable coronary heart disease treated with aspirin - suggesting that "AR" may be mainly caused by lacking drug adherence.
In contrast to aspirin, between-subject variability in responses to clopidogrel therapy may be substantial - a fact that is clinically challenging. In the second study - based on ADP-stimulated LTA among 79 patients treated with percutaneous coronary intervention (PCI) and dual antiplatelet therapy with aspirin and clopidogrel, such between-subject variability was confirmed, and we also found within-subject variations in clopidogrel responses over time - indicating that prediction of aggregometry responses to clopidogrel therapy based on single tests may be unreliable. Our data also indicated that comparisons of aggregometry responses should be performed with caution unless ADP concentrations are standardized.
Although ADP-stimulated LTA might potentially identify patients with percieved inadequate response to clopidogrel, such testing takes hours and can not be implemented in standard clinical settings. Among several much faster tests, Multiple Electrode Aggregometry (MEA) might on the other hand be used clinically, and we therefore wanted to study the agreement between LTA (the "gold standard") and MEA. We also wanted to explore whether aggregation in venous and arterial blood is similar - since arterial blood is the main target of antiplatelet therapy, whereas venous blood is used for testing. In the third and final study we report that MEA and LTA aggregation in arterial and venous blood were similar, and that the agreement between LTA and MEA was good - and stable over time in patients.
Måling av platehemning med hurtigtest vs. klassisk test
Fordi den platehemmende effekten av clopidogrel varierer fra pasient til pasient, er det behov for utvikling av hurtigtester som kan vise hvilke pasienter som har for dårlig effekt. Dette prosjektet undersøker i hvilken grad det er samsvar mellom klassisk Born plateaggregometri (langsom, men nøyaktig test) og en ny hurtigtest (Multiplate).
Prosjektet har til nå resultert i følgende to publikasjoner:
1. Meen O, Brosstad F, Khiabani H, Gjertsen E, Lauritsen ME, Pedersen TM, et al. No case of COX-1-related aspirin resistance found in 289 patients with symptoms of stable CHD remitted for coronary angiography. Scand J Clin Lab Invest 2007 Oct 11;1-10.
2. Meen O, Brosstad F, Bjornsen S, Pedersen TM, Erikssen G. Variability in aggregometry response before and after initiation of clopidogrel therapy. Scand J Clin Lab Invest 2009 May 29;1-7.
En tredje (og siste) publikasjon:
Meen Ø, Brosstad F, Kunszt G, Liestøl K, Bendz B, Wettergreen M, Schjelderup NM, Andreassen T, Erikssen G. Repeated, parallel ADP-stimulated Born and Multiplate aggregometry in patients taking clopidogrel after non ST-elevation myocardial infarction
er i ferd med å bli ferdigstilt.
Undersøkelsen som denne artikkelen bygger på startet i desember 2009, og ble avsluttet i juni 2010.
Det er i 2010 søkt om å få overført midlene fra 2010 til 2011 og 2012, og denne søknaden er innvilget. Utestående utgifter på ca. kr. 140 000,- til Koagulasjonslaboratoriet (2009-2010) er utestående. Resten av beløpet skal brukes av stipendiaten i løpet av 2011 og 2012.
Den siste artikkelen i doktorgradsarbeidet forventes å være klar til første innsending med tanke på publisering senest innen utgangen av mars 2011. Selve doktoravhandlingen planlegges innlevert innen utgangen av 2011.
Doktorgradsarbeidet er blitt noe forsinket i forhold til de opprinnelig oppsatte planer.
Sequential ADP-stimulated light transmission and multiple electrode aggregometry in patients taking aspirin and clopidogrel after non ST-elevation myocardial infarction.
Scand J Clin Lab Invest 2012 Jul;72(4):318-25.
PMID: 22724626 - Inngår i doktorgradsavhandlingen