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Platelet Interactions with Von Willebrand Factor Differ Between Acute and Stable Coronary Syndromes

March 10, 2017-Hong Kong, China — Despite nominal response to dualantiplatelet therapy as measured by light transmittance platelet aggregometry, the profileof dynamic platelet behaviour measured by novel platelet function parameters has beenfound to differ remarkably in patients with acute coronary syndrome vs stable coronaryartery disease.

This finding of a comparative study of platelet function in patients with acute coronarysyndromes vs those with stable coronary artery disease was reported at the 58th AnnualMeeting of the American Society of Hematology, from December 3 – 6.

Eimear Dunne, MSc, of the Royal College of Surgeons in Ireland, Dublin, explained thatin unstable coronary syndromes, von Willebrand factor adheres to exposedsubendothelial matrix. Initial platelet interaction with immobilised von Willebrand factoris rapidly reversible, shear-dependent, and includes characteristic start-stop translocationof platelets.

Platelets tether to bound von Willebrand factor via the glycoprotein Ib receptor andinitiate a complex signaling cascade, ultimately activating the integrin αIIb β3 receptorthat crosslinks fibrinogen and causes platelet arrest.

Ms Dunne and colleagues have developed a microfluidic assay utilising videomicroscopyto accurately measure dynamic platelet behaviour in microliters of blood perfused acrossvon Willebrand factor at arterial shear rates (1500 s-1).

Dermot Kenny, MD, who participated in the study, said, “Unstable coronary syndromesare associated with adverse prognosis. A number of clinical trials using guided antiplatelet therapy have failed to show benefit.”

Tracking multiple individual platelets from frame to frame with unique motion analysissoftware, the assay measures the total number of platelets that:

  1. Interact with von Willebrand factor
  2. Translocate across von Willebrand factor (glycoprotein Ib - dependent)
  3. Stably adhere to the surface (αIIb β3-dependent)

The following were also determined using motion analysis software:

  1. The development rate of thrombi
  2. The percent surface coverage at 17 s (the end of the assay)

Variations in platelet function associated with acute coronary syndromes and stablecoronary artery disease are poorly understood. Ms Dunne and coinvestigatorshypothesised that platelet function would differ between normal donors, patients with
stable coronary artery disease taking aspirin, and patients with acute coronary syndromeson dual antiplatelet therapy.

They characterised dynamic platelet function in 66 healthy donors, 67 patients with stablecoronary artery disease on long-term aspirin alone, and 85 patients recruited within 3days of a cardiac event who were receiving dual antiplatelet therapy (acute coronarysyndromes group).

All patients responded appropriately to either aspirin alone or dual antiplatelet therapy asdefined by consensus guidelines using light transmission aggregometry in response to500 mg/mL arachidonic acid and 20 mM adenosine diphosphate.

Compared to healthy controls and despite an adequate light transmission aggregometricresponse to dual antiplatelet therapy, patients with acute coronary syndromes exhibitedsignificantly more platelets interacting with von Willebrand factor (mean 534 ± 281 vs424 ± 198, p² = .01), stably adhered platelets (237 ± 118 vs 189 ± 69, p² = .01),translocating platelets (365 ± 186 vs 303 ± 141, p² = .04), and final surface coverage (12.8 ± 3.7% vs 11.2 ± 2.7%, p² = .002).

Differences observed between patients with coronary artery disease taking aspirin aloneand those with acute coronary syndromes were even more striking: Patients withcoronary artery disease taking aspirin long-term harboured fewer stably adhered (181 ±83 vs 237 ± 118, p² = .002) and translocating platelets (271 ± 141 vs 365 ± 186, p² =.0006).

Both the rate of thrombus growth (9.8 ± 2.7 vs 8.6 ± 2.7, p² = .005) and percent surfacecoverage (12.8 ± 3.7% vs 10.8 ± 3.4%, p² = .0007) were significantly greater in patientswith acute coronary syndromes.

Ms Dunne concluded that, despite nominal response to dual antiplatelet therapy asmeasured by light transmission aggregometry, the profile of dynamic platelet behaviourmeasured by novel platelet function parameters was found to differ remarkably inpatients with acute coronary syndromes vs those with stable coronary artery disease.

Platelets from patients with acute coronary syndromes interact more with von Willebrandfactor than those from healthy controls and patients with stable coronary artery disease.The dynamic platelet function assay describes novel platelet interactions with vonWillebrand factor for the first time, and suggests a new way to guide antiplatelet therapy.

Dr Kenny said, “The data presented here using a novel diagnostic assay suggests that newdevices may enable more accurate patient characterisation, and hence, personalisedtherapy.”


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