Shear-Induced Platelet Activation is Sensitive to Age and Calcium Availability: A Comparison of Adult and Cord Blood



Antiplatelet therapy for neonates and infants is often extrapolated from the adult experience, based on limited observation of agonist-induced neonatal platelet hypoactivity and poor understanding of flow shear-mediated platelet activation. Therefore, thrombotic events due to device-associated disturbed flow are inadequately mitigated in critically ill neonates with indwelling umbilical catheters and infants receiving cardiovascular implants.


Whole blood (WB), platelet-rich plasma (PRP), and gel-filtered platelets (GFP) were prepared from umbilical cord and adult blood, and exposed to biochemical agonists or pathological shear stress of 70 dyne/cm2. We evaluated α-granule release, phosphatidylserine (PS) scrambling, and procoagulant response using P-selectin expression, Annexin V binding, and thrombin generation (PAS), respectively. Activation modulation due to depletion of intracellular and extracellular calcium, requisite second messengers, was also examined.


Similar P-selectin expression was observed for sheared adult and cord platelets, with concordant inhibition due to intracellular and extracellular calcium depletion. Sheared cord platelet Annexin V binding and PAS activity was similar to adult values in GFP, but lower in PRP and WB. Annexin V on sheared cord platelets was calcium-independent, with PAS slightly reduced by intracellular calcium depletion.


Increased PS activity on purified sheared cord platelets suggest that their intrinsic function under pathological flow conditions is suppressed by cell-cell or plasmatic components. Although secretory functions of adult and cord platelets retain comparable calcium-dependence, PS exposure in sheared cord platelets is uniquely calcium-independent and distinct from adults. Identification of calcium-regulated developmental disparities in shear-mediated platelet function may provide novel targets for age-specific antiplatelet therapy.

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Figure 6



1,2-Bis(o-aminophenoxy)ethane-N,N,N′,N′-tetraacetic acid

\({\text{Ca}}_{\text{int}}^{2 + }\) :

Intracellular calcium-depleted

\({\text{Ca}}_{\text{ext}}^{2 + }\) :

Extracellular calcium-depleted


Integrin αIIb, GPIIb




Gel-filtered platelets


Hemodynamic shearing device


Neonatal intensive care unit


Platelet activation state, a measure of normalized thrombin generation


Platelet-rich plasma




von Willebrand Factor


Whole blood


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The authors gratefully acknowledge Brianne Polehinke for her assistance with the experiments. This work was supported by the National Heart, Lung, and Blood Institute of the National Institutes of Health Grants U01 HL131052 (D. Bluestein) and R01 HL119096 (W.F. Bahou).

Conflict of interest

Jawaad Sheriff, Lisa E. Malone, Cecilia Avila, Amanda Zigomalas, Danny Bluestein, and Wadie F. Bahou declare that they have no conflicts of interest.

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Sheriff, J., Malone, L.E., Avila, C. et al. Shear-Induced Platelet Activation is Sensitive to Age and Calcium Availability: A Comparison of Adult and Cord Blood. Cel. Mol. Bioeng. (2020).

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  • Phosphatidylserine
  • α-Granule release
  • Umbilical cord platelets
  • Thrombosis
  • Shear stress