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

Abstract

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.

This is a preview of subscription content, log in to check access.

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5
Figure 6

Abbreviations

BAPTA:

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

CD41a:

Integrin αIIb, GPIIb

CD62P:

P-selectin

GFP:

Gel-filtered platelets

HSD:

Hemodynamic shearing device

NICU:

Neonatal intensive care unit

PAS:

Platelet activation state, a measure of normalized thrombin generation

PRP:

Platelet-rich plasma

PS:

Phosphatidylserine

vWF:

von Willebrand Factor

WB:

Whole blood

References

  1. 1.

    Antithrombotic Trialists, C., C. Baigent, L. Blackwell, R. Collins, J. Emberson, J. Godwin, R. Peto, J. Buring, C. Hennekens, P. Kearney, T. Meade, C. Patrono, M. C. Roncaglioni, and A. Zanchetti. Aspirin in the primary and secondary prevention of vascular disease: collaborative meta-analysis of individual participant data from randomised trials. Lancet 373:1849–1860, 2009.

    Google Scholar 

  2. 2.

    Arachiche, A., D. Kerbiriou-Nabias, I. Garcin, T. Letellier, and J. Dachary-Prigent. Rapid procoagulant phosphatidylserine exposure relies on high cytosolic calcium rather than on mitochondrial depolarization. Arterioscler. Thromb. Vasc. Biol. 29:1883–1889, 2009.

    Google Scholar 

  3. 3.

    Baker-Groberg, S. M., S. Lattimore, M. Recht, O. J. McCarty, and K. M. Haley. Assessment of neonatal platelet adhesion, activation, and aggregation. J. Thromb. Haemost. 14:815–827, 2016.

    Google Scholar 

  4. 4.

    Bernhard, H., A. Rosenkranz, M. Novak, B. Leschnik, M. Petritsch, T. Rehak, H. Kofeler, D. Ulrich, and W. Muntean. No differences in support of thrombin generation by neonatal or adult platelets. Hamostaseologie 29(Suppl 1):S94–S97, 2009.

    Google Scholar 

  5. 5.

    Bernhard, H., A. Rosenkranz, M. Petritsch, H. Kofeler, T. Rehak, M. Novak, and W. Muntean. Phospholipid content, expression and support of thrombin generation of neonatal platelets. Acta Paediatr. 98:251–255, 2009.

    Google Scholar 

  6. 6.

    Bevers, E. M., P. Comfurius, and R. F. Zwaal. Changes in membrane phospholipid distribution during platelet activation. Biochim. Biophys. Acta 736:57–66, 1983.

    Google Scholar 

  7. 7.

    Bevers, E. M., and P. L. Williamson. Getting to the outer leaflet: physiology of phosphatidylserine exposure at the plasma membrane. Physiol. Rev. 96:605–645, 2016.

    Google Scholar 

  8. 8.

    Caparros-Perez, E., R. Teruel-Montoya, M. J. Lopez-Andreo, M. C. Llanos, J. Rivera, V. Palma-Barqueros, J. E. Blanco, V. Vicente, C. Martinez, and F. Ferrer-Marin. Comprehensive comparison of neonate and adult human platelet transcriptomes. PLoS ONE 12:e0183042, 2017.

    Google Scholar 

  9. 9.

    Caparros-Perez, E., R. Teruel-Montoya, V. Palma-Barquero, J. M. Torregrosa, J. E. Blanco, J. L. Delgado, M. L. Lozano, V. Vicente, M. Sola-Visner, J. Rivera, C. Martinez, and F. Ferrer-Marin. Down regulation of the Munc18b-syntaxin-11 complex and beta1-tubulin impairs secretion and spreading in neonatal platelets. Thromb. Haemost. 117:2079–2091, 2017.

    Google Scholar 

  10. 10.

    Casa, L. D. C., S. E. Gillespie, S. L. Meeks, and D. N. Ku. Relative contributions of von willebrand factor and platelets in high shear thrombosis. J. Hematol. Thromboembolic Dis. 4:1–8, 2016.

    Google Scholar 

  11. 11.

    Casa, L. D. C., and D. N. Ku. Thrombus formation at high shear rates. Annu. Rev. Biomed. Eng. 19:415–433, 2017.

    Google Scholar 

  12. 12.

    Chen, Z., N. K. Mondal, J. Ding, S. C. Koenig, M. S. Slaughter, B. P. Griffith, and Z. J. Wu. Activation and shedding of platelet glycoprotein IIb/IIIa under non-physiological shear stress. Mol. Cell. Biochem. 409:93–101, 2015.

    Google Scholar 

  13. 13.

    Cvirn, G., S. Gallistl, T. Rehak, G. Jurgens, and W. Muntean. Elevated thrombin-forming capacity of tissue factor-activated cord compared with adult plasma. J. Thromb. Haemost. 1:1785–1790, 2003.

    Google Scholar 

  14. 14.

    Ensor, C. R., C. A. Paciullo, W. D. Cahoon, Jr, and P. E. Nolan, Jr. Pharmacotherapy for mechanical circulatory support: a comprehensive review. Ann. Pharmacother. 45:60–77, 2011.

    Google Scholar 

  15. 15.

    Flaumenhaft, R. Molecular basis of platelet granule secretion. Arterioscler. Thromb. Vasc. Biol. 23:1152–1160, 2003.

    Google Scholar 

  16. 16.

    Flaumenhaft, R., K. Croce, E. Chen, B. Furie, and B. C. Furie. Proteins of the exocytotic core complex mediate platelet alpha-granule secretion: Roles of vesicle-associated membrane protein, SNAP-23, and syntaxin 4. J Biol Chem. 274:2492–2501, 1999.

    Google Scholar 

  17. 17.

    Fritsch, P., G. Cvirn, C. Cimenti, K. Baier, S. Gallistl, M. Koestenberger, B. Roschitz, B. Leschnik, and W. Muntean. Thrombin generation in factor VIII-depleted neonatal plasma: nearly normal because of physiologically low antithrombin and tissue factor pathway inhibitor. J. Thromb. Haemost. 4:1071–1077, 2006.

    Google Scholar 

  18. 18.

    Gelman, B., B. N. Setty, D. Chen, S. Amin-Hanjani, and M. J. Stuart. Impaired mobilization of intracellular calcium in neonatal platelets. Pediatr. Res. 39:692–696, 1996.

    Google Scholar 

  19. 19.

    Girdhar, G., M. Xenos, Y. Alemu, W. C. Chiu, B. E. Lynch, J. Jesty, S. Einav, M. J. Slepian, and D. Bluestein. Device thrombogenicity emulation: a novel method for optimizing mechanical circulatory support device thromboresistance. PLoS ONE 7:e32463, 2012.

    Google Scholar 

  20. 20.

    Goncalves, I., W. S. Nesbitt, Y. Yuan, and S. P. Jackson. Importance of temporal flow gradients and integrin alphaIIbbeta3 mechanotransduction for shear activation of platelets. J. Biol. Chem. 280:15430–15437, 2005.

    Google Scholar 

  21. 21.

    Grinstein, S., and W. Furuya. Binding of 125I-calmodulin to platelet alpha-granules. FEBS Lett. 140:49–52, 1982.

    Google Scholar 

  22. 22.

    Haga, J. H., S. M. Slack, and L. K. Jennings. Comparison of shear stress-induced platelet microparticle formation and phosphatidylserine expression in presence of alphaIIbbeta3 antagonists. J. Cardiovasc. Pharmacol. 41:363–371, 2003.

    Google Scholar 

  23. 23.

    Hellums, J. D. 1993 Whitaker Lecture: biorheology in thrombosis research. Ann. Biomed. Eng. 22:445–455, 1994.

    Google Scholar 

  24. 24.

    Ilkan, Z., J. R. Wright, A. H. Goodall, J. M. Gibbins, C. I. Jones, and M. P. Mahaut-Smith. Evidence for shear-mediated Ca(2+) entry through mechanosensitive cation channels in human platelets and a megakaryocytic cell line. J. Biol. Chem. 292:9204–9217, 2017.

    Google Scholar 

  25. 25.

    Israels, S. J., M. L. Rand, and A. D. Michelson. Neonatal platelet function. Semin. Thromb. Hemost. 29:363–372, 2003.

    Google Scholar 

  26. 26.

    Ivetic, N., D. M. Arnold, J. W. Smith, A. Huynh, J. G. Kelton, and I. Nazy. A platelet viability assay (PVA) for the diagnosis of heparin-induced thrombocytopenia. Platelets 30:1017–1021, 2019.

    Google Scholar 

  27. 27.

    Jackson, S. P. Arterial thrombosis—insidious, unpredictable and deadly. Nat. Med. 17:1423–1436, 2011.

    Google Scholar 

  28. 28.

    Jesty, J., and D. Bluestein. Acetylated prothrombin as a substrate in the measurement of the procoagulant activity of platelets: elimination of the feedback activation of platelets by thrombin. Anal. Biochem. 272:64–70, 1999.

    Google Scholar 

  29. 29.

    Jones, C. I. Platelet function and ageing. Mamm. Genome 27:358–366, 2016.

    Google Scholar 

  30. 30.

    Knight, D. E., and M. C. Scrutton. Direct evidence for a role for Ca2+ in amine storage granule secretion by human platelets. Thromb. Res. 20:437–446, 1980.

    Google Scholar 

  31. 31.

    Kroll, M. H., J. D. Hellums, L. V. McIntire, A. I. Schafer, and J. L. Moake. Platelets and shear stress. Blood 88:1525–1541, 1996.

    Google Scholar 

  32. 32.

    Lemons, P. P., D. Chen, and S. W. Whiteheart. Molecular mechanisms of platelet exocytosis: requirements for alpha-granule release. Biochem. Biophys. Res. Commun. 267:875–880, 2000.

    Google Scholar 

  33. 33.

    Levy-Shraga, Y., A. Maayan-Metzger, A. Lubetsky, B. Shenkman, J. Kuint, U. Martinowitz, and G. Kenet. Platelet function of newborns as tested by cone and plate(let) analyzer correlates with gestational age. Acta Haematol. 115:152–156, 2006.

    Google Scholar 

  34. 34.

    Leytin, V., D. J. Allen, S. Mykhaylov, L. Mis, E. V. Lyubimov, B. Garvey, and J. Freedman. Pathologic high shear stress induces apoptosis events in human platelets. Biochem. Biophys. Res. Commun. 320:303–310, 2004.

    Google Scholar 

  35. 35.

    McNeil, J. J., R. L. Woods, M. R. Nelson, C. M. Reid, B. Kirpach, R. Wolfe, E. Storey, R. C. Shah, J. E. Lockery, A. M. Tonkin, A. B. Newman, J. D. Williamson, K. L. Margolis, M. E. Ernst, W. P. Abhayaratna, N. Stocks, S. M. Fitzgerald, S. G. Orchard, R. E. Trevaks, L. J. Beilin, G. A. Donnan, P. Gibbs, C. I. Johnston, J. Ryan, B. Radziszewska, R. Grimm, A. M. Murray, and A.I. Group. Effect of aspirin on disability-free survival in the healthy elderly. N Engl J Med. 379:1499–1508, 2018.

    Google Scholar 

  36. 36.

    Metharom, P., M. C. Berndt, R. I. Baker, and R. K. Andrews. Current state and novel approaches of antiplatelet therapy. Arterioscler. Thromb. Vasc. Biol. 35:1327–1338, 2015.

    Google Scholar 

  37. 37.

    Michelson, A. D., D. Rajasekhar, F. J. Bednarek, and M. R. Barnard. Platelet and platelet-derived microparticle surface factor V/Va binding in whole blood: differences between neonates and adults. Thromb. Haemost. 84:689–694, 2000.

    Google Scholar 

  38. 38.

    Monagle, P., A. K. C. Chan, N. A. Goldenberg, R. N. Ichord, J. M. Journeycake, U. Nowak-Gottl, and S. K. Vesely. Antithrombotic therapy in neonates and children: antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest 141:e737S–e801S, 2012.

    Google Scholar 

  39. 39.

    Muntean, W., B. Leschnik, K. Baier, G. Cvirn, and S. Gallistl. In vivo thrombin generation in neonates. J. Thromb. Haemost. 2:2071–2072, 2004.

    Google Scholar 

  40. 40.

    Ngo, A. T. P., J. Sheriff, A. D. Rocheleau, M. Bucher, K. R. Jones, A. I. Sepp, L. E. Malone, A. Zigomalas, A. Maloyan, W. F. Bahou, D. Bluestein, O. J. T. McCarty, and K. M. Haley. Assessment of neonatal, cord, and adult platelet granule trafficking and secretion. Platelets 31:68–78, 2020.

    Google Scholar 

  41. 41.

    Nobili, M., J. Sheriff, U. Morbiducci, A. Redaelli, and D. Bluestein. Platelet activation due to hemodynamic shear stresses: damage accumulation model and comparison to in vitro measurements. ASAIO J. 54:64–72, 2008.

    Google Scholar 

  42. 42.

    Pichler, E., and L. Pichler. The neonatal coagulation system and the vitamin K deficiency bleeding—a mini review. Wien. Med. Wochenschr. 158:385–395, 2008.

    Google Scholar 

  43. 43.

    Qiu, Y., J. Ciciliano, D. R. Myers, R. Tran, and W. A. Lam. Platelets and physics: How platelets “feel” and respond to their mechanical microenvironment. Blood Rev. 29:377–386, 2015.

    Google Scholar 

  44. 44.

    Receveur, N., D. Nechipurenko, Y. Knapp, A. Yakusheva, E. Maurer, C. V. Denis, F. Lanza, M. Panteleev, C. Gachet, and P. H. Mangin. Shear rate gradients promote a bi-phasic thrombus formation on weak adhesive proteins, such as fibrinogen in a VWF-dependent manner. Haematologica 2019. https://doi.org/10.3324/haematol.2019.235754.

  45. 45.

    Rehak, T., G. Cvirn, S. Gallistl, B. Leschnik, M. Kostenberger, H. Katzer, V. Ribitsch, and W. Muntean. Increased shear stress- and ristocetin-induced binding of von Willebrand factor to platelets in cord compared with adult plasma. Thromb. Haemost. 92:682–687, 2004.

    Google Scholar 

  46. 46.

    Rice, N. T., F. Szlam, J. D. Varner, P. S. Bernstein, A. D. Szlam, and K. A. Tanaka. Differential contributions of intrinsic and extrinsic pathways to thrombin generation in adult, maternal and cord plasma samples. PLoS ONE 11:e0154127, 2016.

    Google Scholar 

  47. 47.

    Roka-Moiia, Y., R. Walk, D. E. Palomares, K. R. Ammann, A. Dimasi, J. E. Italiano, J. Sheriff, D. Bluestein, and M. J. Slepian. Platelet activation via shear stress exposure induces a differing pattern of biomarkers of activation versus biochemical agonists. Thromb. Haemost. 120:776–792, 2020.

    Google Scholar 

  48. 48.

    Roschitz, B., K. Sudi, M. Kostenberger, and W. Muntean. Shorter PFA-100 closure times in neonates than in adults: role of red cells, white cells, platelets and von Willebrand factor. Acta Paediatr. 90:664–670, 2001.

    Google Scholar 

  49. 49.

    Ruggeri, Z. M. Von. Willebrand factor: looking back and looking forward. Thromb. Haemost. 98:55–62, 2007.

    Google Scholar 

  50. 50.

    Ruggeri, Z. M., J. N. Orje, R. Habermann, A. B. Federici, and A. J. Reininger. Activation-independent platelet adhesion and aggregation under elevated shear stress. Blood 108:1903–1910, 2006.

    Google Scholar 

  51. 51.

    Sakariassen, K. S., P. A. Holme, U. Orvim, R. M. Barstad, N. O. Solum, and F. R. Brosstad. Shear-induced platelet activation and platelet microparticle formation in native human blood. Thromb. Res. 92:S33–S41, 1998.

    Google Scholar 

  52. 52.

    Saving, K. L., D. E. Jennings, J. C. Aldag, and R. C. Caughey. Platelet ultrastructure of high-risk premature infants. Thromb. Res. 73:371–384, 1994.

    Google Scholar 

  53. 53.

    Saxonhouse, M. A., R. Garner, L. Mammel, Q. Li, K. E. Muller, J. Greywoode, C. Miller, and M. Sola-Visner. Closure times measured by the platelet function analyzer PFA-100 are longer in neonatal blood compared to cord blood samples. Neonatology 97:242–249, 2010.

    Google Scholar 

  54. 54.

    Schoenwaelder, S. M., Y. Yuan, E. C. Josefsson, M. J. White, Y. Yao, K. D. Mason, L. A. O’Reilly, K. J. Henley, A. Ono, S. Hsiao, A. Willcox, A. W. Roberts, D. C. Huang, H. H. Salem, B. T. Kile, and S. P. Jackson. Two distinct pathways regulate platelet phosphatidylserine exposure and procoagulant function. Blood 114:663–666, 2009.

    Google Scholar 

  55. 55.

    Schulz-Heik, K., J. Ramachandran, D. Bluestein, and J. Jesty. The extent of platelet activation under shear depends on platelet count: differential expression of anionic phospholipid and factor Va. Pathophysiol. Haemost. Thromb. 34:255–262, 2005.

    Google Scholar 

  56. 56.

    Schweintzger, S., A. Schlagenhauf, B. Leschnik, B. Rinner, H. Bernhard, M. Novak, and W. Muntean. Microparticles in newborn cord blood: slight elevation after normal delivery. Thromb. Res. 128:62–67, 2011.

    Google Scholar 

  57. 57.

    Shenkman, B., N. Linder, N. Savion, I. Tamarin, R. Dardik, G. Kennet, B. German, and D. Varon. Increased neonatal platelet deposition on subendothelium under flow conditions: the role of plasma von Willebrand factor. Pediatr. Res. 45:270–275, 1999.

    Google Scholar 

  58. 58.

    Sheriff, J., D. Bluestein, G. Girdhar, and J. Jesty. High-shear stress sensitizes platelets to subsequent low-shear conditions. Ann. Biomed. Eng. 38:1442–1450, 2010.

    Google Scholar 

  59. 59.

    Sheriff, J., J. S. Soares, M. Xenos, J. Jesty, and D. Bluestein. Evaluation of shear-induced platelet activation models under constant and dynamic shear stress loading conditions relevant to devices. Ann. Biomed. Eng. 41:1279–1296, 2013.

    Google Scholar 

  60. 60.

    Sitaru, A. G., S. Holzhauer, C. P. Speer, D. Singer, A. Obergfell, U. Walter, and R. Grossmann. Neonatal platelets from cord blood and peripheral blood. Platelets 16:203–210, 2005.

    Google Scholar 

  61. 61.

    Slepian, M. J., J. Sheriff, M. Hutchinson, P. Tran, N. Bajaj, J. G. N. Garcia, S. Scott Saavedra, and D. Bluestein. Shear-mediated platelet activation in the free flow: Perspectives on the emerging spectrum of cell mechanobiological mechanisms mediating cardiovascular implant thrombosis. J Biomech. 50:20–25, 2017.

    Google Scholar 

  62. 62.

    Sola-Visner, M. Platelets in the neonatal period: developmental differences in platelet production, function, and hemostasis and the potential impact of therapies. Hematol Am Soc Hematol Educ Program. 506–511:2012, 2012.

    Google Scholar 

  63. 63.

    Stokhuijzen, E., J. M. Koornneef, B. Nota, B. L. van den Eshof, F. P. J. van Alphen, M. van den Biggelaar, C. van der Zwaan, C. Kuijk, K. Mertens, K. Fijnvandraat, and A. B. Meijer. Differences between platelets derived from neonatal cord blood and adult peripheral blood assessed by mass spectrometry. J. Proteome Res. 16:3567–3575, 2017.

    Google Scholar 

  64. 64.

    Suzuki, J., D. P. Denning, E. Imanishi, H. R. Horvitz, and S. Nagata. Xk-related protein 8 and CED-8 promote phosphatidylserine exposure in apoptotic cells. Science 341:403–406, 2013.

    Google Scholar 

  65. 65.

    Suzuki, J., M. Umeda, P. J. Sims, and S. Nagata. Calcium-dependent phospholipid scrambling by TMEM16F. Nature 468:834–838, 2010.

    Google Scholar 

  66. 66.

    Tesfamariam, B. Distinct characteristics of neonatal platelet reactivity. Pharmacol. Res. 123:1–9, 2017.

    Google Scholar 

  67. 67.

    Valerio, L., J. Sheriff, P. L. Tran, W. Brengle, A. Redaelli, G. B. Fiore, F. Pappalardo, D. Bluestein, and M. J. Slepian. Routine clinical anti-platelet agents have limited efficacy in modulating hypershear-mediated platelet activation associated with mechanical circulatory support. Thromb. Res. 163:162–171, 2018.

    Google Scholar 

  68. 68.

    Valerio, L., P. L. Tran, J. Sheriff, W. Brengle, R. Ghosh, W. C. Chiu, A. Redaelli, G. B. Fiore, F. Pappalardo, D. Bluestein, and M. J. Slepian. Aspirin has limited ability to modulate shear-mediated platelet activation associated with elevated shear stress of ventricular assist devices. Thromb. Res. 140:110–117, 2016.

    Google Scholar 

  69. 69.

    van Kruchten, R., N. J. Mattheij, C. Saunders, M. A. Feijge, F. Swieringa, J. L. Wolfs, P. W. Collins, J. W. Heemskerk, and E. M. Bevers. Both TMEM16F-dependent and TMEM16F-independent pathways contribute to phosphatidylserine exposure in platelet apoptosis and platelet activation. Blood 121:1850–1857, 2013.

    Google Scholar 

  70. 70.

    White, J. G. Effects of an ionophore, A23187, on the surface morphology of normal erythrocytes. Am. J. Pathol. 77:507–518, 1974.

    Google Scholar 

  71. 71.

    Will, A. Neonatal haemostasis and the management of neonatal thrombosis. Br. J. Haematol. 169:324–332, 2015.

    Google Scholar 

  72. 72.

    Xenos, M., G. Girdhar, Y. Alemu, J. Jesty, M. Slepian, S. Einav, and D. Bluestein. Device Thrombogenicity Emulator (DTE) - Design optimization methodology for cardiovascular devices: a study in two bileaflet MHV designs. J. Biomech. 43:2400–2409, 2010.

    Google Scholar 

  73. 73.

    Zwaal, R. F., P. Comfurius, and E. M. Bevers. Surface exposure of phosphatidylserine in pathological cells. Cell. Mol. Life Sci. 62:971–988, 2005.

    Google Scholar 

Download references

Acknowledgments

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.

Research Involving Human and Animal Participants

All human studies were carried out in accordance with institutional guidelines and approved by the Stony Brook University Institutional Review Board (2012-4427-FAR and 2016-5886-R1). No animal studies were carried out by the authors for this article.

Informed Consent

Informed consent was obtained from all subjects included in the study.

Author information

Affiliations

Authors

Corresponding author

Correspondence to Jawaad Sheriff.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Associate Editor Judith Cosemans oversaw the review of this article.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

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). https://doi.org/10.1007/s12195-020-00628-x

Download citation

Keywords

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