Introduction: Patients with coronary artery disease (CAD) are treated with aspirin and a P2Y12 antagonist to prevent myocardial infarction or stent thrombosis. Variable clinical response to both types of agents has been reported. Existing assays to identify sub-optimal response to anti-platelet therapy do not meet reported medical needs.

Aim: To characterize the utility of a synthetic collagen (SynC) to monitor platelet function in patients on dual-antiplatelet therapy.

Methods: Blood samples from healthy individuals (n=5) and CAD patients treated with clopidogrel (75-600 mg) with or without aspirin (75-325 mg) (n=51) were centrifuged to produce plasmas for aggregometry studies (PAP 8E, Bio/Data Corp. Horsham, PA). The aggregation response to 20 µM ADP, 500 µg/ml arachidonic acid and 190 µg/ml Type 1 biologic collagen was compared to that induced by SynC (2-200 ng/ml; JNC Corp., Yokohama, Japan). The aggregation response was characterized in terms of % aggregation, slope and AUC.

Results: The average age of the enrolled patients was 65.8 years (range: 48-83 years); 35 were male and 16 were female. CAD patients exhibited the common co-morbidities of hypertension (65%), hypercholesterolemia (55%), diabetes (37.3%) and obesity (10%) and as such received concomitant treatment with β-blockers (73%), ACE inhibitors (25%), calcium channel blockers (22%), statins (84%) and anti-diabetics (47%). Using plasmas from healthy individuals and CAD patients, two lots of SynC produced a concentration-dependent aggregation response over a concentration range of 16 to 128 ng/ml. Patients treated with 81 mg aspirin and 75 mg clopidogrel (33 of 51 patients) were stratified into two groups based on their % aggregation response to SynC, using the median % aggregation as the cut point. While the two groups had a distinct response to SynC, the median responses to ADP, arachidonic acid and biologic collagen were nearly the same and there was a strong overlap between the responses to these agonists in the two sub-groups. This is most evident at the lower concentrations of SynC.

Conclusions: SynC-induced platelet aggregation may identify sub-groups of patients with sub-optimal response to dual antiplatelet therapy that go undetected with traditional platelet agonists. Studies to clarify why biologic and synthetic collagens have different sensitivities to aspirin and clopidogrel are warranted.

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Disclosures

No relevant conflicts of interest to declare.

Topics:
collagen, dual anti-platelet therapy, platelet function, obesity, aspirin, clopidogrel, agonists, arachidonic acid, diabetes mellitus, angiotensin-converting enzyme inhibitors

Author notes

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Asterisk with author names denotes non-ASH members.

© 2017 by The American Society of Hematology
2017
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