High Platelet Reactivity Despite Taking Adenosine Diphosphate Receptor Inhibitors: Do We Need to Care?

2021 ◽  
Author(s):  
Håkan N. Pärsson
Keyword(s):  
Platelet Reactivity ◽  
Adenosine Diphosphate ◽  
High Platelet Reactivity

scholarly journals Does the VerifyNow P2Y12 assay overestimate “therapeutic response” to clopidogrel?

2014 ◽  
Vol 111 (06) ◽  
pp. 1150-1159 ◽  
Author(s):  
Vikram Khanna ◽  
Alex Hobson ◽  
Rand Mikael ◽  
Nalyaka Sambu ◽  
Nicola Englyst ◽  
...  
Keyword(s):  
Platelet Aggregation ◽  
Healthy Volunteers ◽  
Prostaglandin E1 ◽  
Therapeutic Response ◽  
Platelet Reactivity ◽  
Adenosine Diphosphate ◽  
Therapeutic Effects ◽  
P2y12 Inhibitors ◽  
High Platelet Reactivity

SummaryIn contrast to short thrombelastography (s-TEG) which utilises adenosine diphosphate (ADP) alone, the VerifyNow P2Y12 assay (VN-P2Y12) additionally uses prostaglandin E1 (PGE1) as agonist to assess response to P2Y12 inhibitors. Based upon previous observations, we hypothesised that VN-P2Y12 overestimates the therapeutic effects of clopidogrel. Simultaneous assay with s-TEG and VN-P2Y12 was performed in 43 healthy volunteers and 170 patients either on or off clopidogrel. Furthermore, in 27 patients on clopidogrel 75 mg we compared the effects of adding 22 nM PGE1 to ADP on platelet aggregation in s-TEG to ADP alone. A higher proportion of individuals had a result indicating high platelet reactivity (HPR) with s-TEG than VN-P2Y12 in (i) 43 clopidogrel naïve volunteers (95.3% vs 81.4%, p = NS); (ii) 28 volunteers loaded with clopidogrel 600 mg (39.3% vs 10.7 %, p = < 0.01); (iii) 123 clopidogrel naïve patients (93.5% vs 78%, p = < 0.0001); (iv) 47 patients on clopidogrel 75 mg (42.6% vs 4.3%, p = < 0.0001). In 59 patients loaded with clopidogrel 600 mg/900 mg, a greater proportion had a “therapeutic response” with VN-P2Y12 compared to s-TEG, regardless of the threshold for defining HPR with VN-PY12 (P2Y12 reaction units ≥ 230 or 208). Furthermore, adding PGE1 to ADP in s-TEG potentiated the anti-aggregatory effects of clopidogrel compared with ADP alone. In conclusion, VN-P2Y12 overestimates the functional effects of clopidogrel in some individuals, possibly because it utilises PGE1 in addition to ADP. This could have implications for the ability of VN-P2Y12 to stratify patients as “responders” or “non-responders” to clopidogrel.

Platelet Behaviour in Non-Insulin-Dependent Diabetes -Influence of Vascular Complications, Treatment and Metabolic Control

1986 ◽  
Vol 55 (03) ◽  
pp. 361-365 ◽  
Author(s):  
I Peacock ◽  
M Hawkins ◽  
S Heptinstall
Keyword(s):  
Blood Glucose ◽  
Metabolic Control ◽  
Platelet Reactivity ◽  
Platelet Rich Plasma ◽  
Vascular Complications ◽  
Adenosine Diphosphate ◽  
Glycosylated Haemoglobin ◽  
Insulin Dependent Diabetes ◽  
Lipid Levels ◽  
Insulin Dependent

SummaryPlatelet-rich plasma was prepared from 47 patients with noninsulin-dependent diabetes treated with glibenclamide and metformin, and 21 controls. The release of radio-labelled 5-hydroxy-tryptamine in response to aggregating agents (adenosine diphosphate, adrenaline and sodium arachidonate), and the effects on release of a selective thromboxane inhibitor (UK-34787) were investigated. Subsequently, 20 of the diabetic subjects were chosen at random for treatment with insulin; the remainder continued to take tablets. Platelet studies were then repeated, in all patients, after 4 and 6 months.The results showed an association between platelet behaviour and the presence of vascular complications, and were consistent with previous observations of reduced platelet reactivity in patients taking sulphonylureas. There was no correlation of platelet reactivity with blood glucose, glycosylated haemoglobin or lipid levels.

Interactions Between Blood Platelets and Vascular Endothelium in vitro Studies

1979 ◽  
Author(s):  
M.A. Gimbrone ◽  
K.D. Curwen ◽  
R. I. Handin
Keyword(s):  
Platelet Aggregation ◽  
Vascular Endothelium ◽  
Potent Inhibitor ◽  
Platelet Reactivity ◽  
Blood Platelets ◽  
Primary Cultures ◽  
Adenosine Diphosphate ◽  
Human Platelets ◽  
Platelet Adherence

Endothelial cells (EC) can actively influence the hemostatic response at sites of vascular injury through multiple mechanisms. For example, EC can degrade adenosine diphosphate, release plasminogen activator, and synthesize prostacyclin (PGI2), a potent inhibitor of platelet aggregation. We have examined whether PGI2 also might account for the normal lack of platelet adherence to the uninjured EC surface. In a monolayer adherence assay, radiolabeled human platelets in citrated plasma showed minimal interaction with primary cultures of human EC (<1 platelet adhering per cell). Platelets from aspirin-treated and untreated donors behaved similarly. However, aspirin pretreatment of EC consistently resulted in ~2-fold increases in platelet adherence which could be completely abolished by exogenous PGI2 (0.5–1.0 μg/ml). SV40-transformed human EC (SVHEC), which are deficient in PGI2 production compared to primary EC, showed 10-30 times more platelet adherence. Exogenous PGI2 produced a dose - related (.001-1.0 μg/ml) decrease in platelet adherence to SVHEC but did not result in the basal levels observed with normal EC monolayers. These data suggest that : 1) In addition to its effects on platelet aggregation, PGI2 can influence platelet endothelial cell interactions; 2) The increased platelet reactivity of transformed EC is associated with, but not completely attributable, to decreased PGI2 production; and 3) Factors other than PGI2 may play a role in the thromboresistance of normal vascular endothelium.

scholarly journals Clinical outcomes in patients treated for coronary in-stent restenosis with drug-eluting balloons: Impact of high platelet reactivity

PLoS ONE ◽  
2017 ◽  
Vol 12 (12) ◽  
pp. e0188493 ◽  
Author(s):  
Adrienn Tornyos ◽  
Dániel Aradi ◽  
Iván G. Horváth ◽  
Attila Kónyi ◽  
Balázs Magyari ◽  
...  
Keyword(s):  
Clinical Outcomes ◽  
Platelet Reactivity ◽  
High Platelet Reactivity ◽  
Stent Restenosis ◽  
Drug Eluting ◽  
In Stent Restenosis

scholarly journals How to react to high platelet reactivity?

2008 ◽  
Vol 29 (11) ◽  
pp. 1471-1471
Author(s):  
N. Clappers ◽  
M. A. Brouwer ◽  
F. W.A. Verheugt
Keyword(s):  
Platelet Reactivity ◽  
High Platelet Reactivity

Abstract 3472: The Prediction of Ischemic Events After Percutaneous Coronary Intervention by Platelet Reactivity to Adenosine Diphosphate: First Evidence for an Oral Antiplatelet Therapeutic Target Determined by an Ex Vivo Test of Platelet Function.

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Paul Gurbel ◽  
Kevin P Bliden ◽  
Joseph Dichiara ◽  
Mark J Antonino ◽  
Thomas A Suarez ◽  
...  
Keyword(s):  
Percutaneous Coronary Intervention ◽  
Risk Factor ◽  
Antiplatelet Therapy ◽  
Therapeutic Target ◽  
Ex Vivo ◽  
Platelet Reactivity ◽  
Adenosine Diphosphate ◽  
Coronary Intervention ◽  
Percutaneous Coronary ◽  
Ischemic Events

Background: High on-treatment platelet reactivity to adenosine diphosphate (HPR-ADP) may be a risk factor for ischemic events after percutaneous coronary intervention (PCI). We determined whether a cutpoint of HPR-ADP, similar to the INR used to guide anticoagulant therapy, could predict ischemic event occurrence after PCI. Methods : Post-procedural platelet reactivity to ADP was measured by conventional aggregometry in 352 consecutive patients undergoing non-emergent PCI followed for up to 2 years for post-discharge ischemic events. All patients had received clopidogrel and aspirin therapy at the time of aggregation measurements. Results: Eighty-two patients (23%) suffered ischemic events and had higher 5 and 20 μM ADP-induced aggregation compared to patients without ischemic events (46 ± 14% and 60 ± 13% versus 30 ± 17% and 43 ± 19%, respectively, p<0.0001 for both measurements). Using a combined receiver operator curve analysis, HPR-ADP cutpoints of 46% aggregation following 5μM ADP stimulation and 59% aggregation following 20μM ADP stimulation were associated with 63% and 74% of ischemic events, respectively. Multivariate Cox regression demonstrated significance between events and post-procedural HPR-ADP cutpoints (20μM ADP, OR=8.6, p<0.0001; and 5μM ADP, OR=2.9, p=0.01). Conclusions: High on-treatment platelet reactivity to ADP is an independent risk factor for ischemic events within 2 years of non-emergent PCI. These data are the first to support a therapeutic target for antiplatelet therapy based on an ex vivo platelet function test, similar to the INR used for anticoagulant therapy. The study is a step towards a personalized medicine approach to guide the intensity of antiplatelet therapy.

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