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Updated: Nov 27, 2025
A Uniform Shear Assay for Human Platelet and Cell Surface Receptors via Cone-plate Viscometry
Published on: June 5, 2019
Shear-Induced Platelet Activation is Sensitive to Age and Calcium Availability: A Comparison of Adult and Cord Blood
Jawaad Sheriff1, Lisa E Malone2, Cecilia Avila3
1Department of Biomedical Engineering, T08-50 Health Sciences Center, Stony Brook University, Stony Brook, NY 11794-8084 USA.
Insights
Neonatal platelets show distinct calcium-independent phosphatidylserine exposure under shear stress compared to adults. This difference in platelet activation may inform age-specific antiplatelet therapies for infants.
Area of Science:
- Hematology
- Pediatric Thrombosis
- Platelet Physiology
Background:
- Current antiplatelet therapy for neonates and infants relies on adult data, overlooking developmental differences in platelet function.
- Critically ill neonates and infants with medical devices face inadequate mitigation of thrombotic events due to disturbed flow.
Purpose of the Study:
- To investigate shear-mediated platelet activation in neonates versus adults.
- To understand the role of calcium in neonatal platelet responses to pathological flow.
- To identify potential targets for age-specific antiplatelet strategies.
Main Methods:
- Prepared whole blood (WB), platelet-rich plasma (PRP), and gel-filtered platelets (GFP) from umbilical cord and adult blood.
- Exposed platelets to agonists or shear stress (70 dyne/cm²).
- Assessed α-granule release, phosphatidylserine (PS) scrambling, and procoagulant response (PAS) via P-selectin expression and Annexin V binding, examining calcium's role.
Main Results:
- Sheared adult and cord platelets showed similar P-selectin expression, both inhibited by calcium depletion.
- Annexin V binding and PAS activity in sheared cord platelets were lower in WB and PRP compared to adults, but similar in GFP.
- Annexin V exposure on sheared cord platelets was calcium-independent, unlike adults.
Conclusions:
- Neonatal platelet function under pathological flow is suppressed by plasma or cell-cell interactions.
- While secretory functions are calcium-dependent in both groups, PS exposure in sheared neonatal platelets is uniquely calcium-independent.
- Developmental disparities in calcium-regulated shear-mediated platelet function offer novel targets for infant-specific antiplatelet therapy.
Introduction:
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.
Methods:
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.
Results:
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.
Conclusions:
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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