Download PDF
Thromb Haemost 2004; 92(04): 682-687
DOI: 10.1160/TH04-05-0270
Theme Issue Article
Schattauer GmbH

Increased shear stress- and ristocetin-induced binding of von Willebrand factor to platelets in cord compared with adult plasma

Thomas Rehak
1   Ludwig Boltzmann Research Institute for Pediatric Hemostasis and Thrombosis, Graz, Austria
2   Department of Pediatrics, Medical University of Graz, Graz, Austria
,
Gerhard Cvirn
3   Institute of Medical Chemistry and Pregl Laboratory, Medical University of Graz, Graz, Austria
,
Siegfried Gallistl
1   Ludwig Boltzmann Research Institute for Pediatric Hemostasis and Thrombosis, Graz, Austria
2   Department of Pediatrics, Medical University of Graz, Graz, Austria
,
Bettina Leschnik
1   Ludwig Boltzmann Research Institute for Pediatric Hemostasis and Thrombosis, Graz, Austria
,
Martin Köstenberger
1   Ludwig Boltzmann Research Institute for Pediatric Hemostasis and Thrombosis, Graz, Austria
2   Department of Pediatrics, Medical University of Graz, Graz, Austria
,
Helga Katzer
4   Institute of Chemistry, Colloid Science and Rheology, Karl Franzens University of Graz, Graz, Austria
,
Volker Ribitsch
4   Institute of Chemistry, Colloid Science and Rheology, Karl Franzens University of Graz, Graz, Austria
,
Wolfgang Muntean
1   Ludwig Boltzmann Research Institute for Pediatric Hemostasis and Thrombosis, Graz, Austria
2   Department of Pediatrics, Medical University of Graz, Graz, Austria
› Author Affiliations
Further Information

Publication History

Received 03 May 2004

Accepted after revision 08 August 2004

Publication Date:
06 December 2017 (online)

    Permissions and Reprints

Summary

Multiple indications do exist that the extensive neonatal platelet adhesion and aggregation, and the shorter closure time of neonatal compared with adult whole blood in the platelet function analyzer 100 are attributable to the physiological high plasma concentrations and high concentrations of unusually large von Willebrand factor (vWf) multimers in neonates. However, to date the direct experimental evidence is lacking. Therefore, we compared in the present study the ability of neonatal vWf to bind to platelets to that of adult vWf. Platelet-poor plasma of neonatal or adult origin, containing antibody-stained vWf, was incubated with neonatal or adult platelet suspension. Subsequently, vWf-platelet interaction was induced by exposing the mixture to shear stress by means of a cone/plate measuring system or by incubating the mixture with ristocetin. Finally, samples were analyzed in a FAC Scan flow cytometer. Detected fluorescence intensities directly correlate with the amount of vWf attached to the platelet surface. We found that significantly higher amounts of neonatal vWf were attached to platelets in the presence of shear stress or ristocetin.This efficient neonatal vWf-platelet interaction is an effect intrinsic to the neonatal vWf, and not to the neonatal platelet: the amount of neonatal vWf attached to neonatal platelets was not different from the amount of neonatal vWf attached to adult platelets. Furthermore, decreasing the vWf content in cord plasma to adult level resulted in significantly suppressed vWf-platelet attachment in the presence of ristocetin, indicating that the high neonatal vWf level contributes to the efficient vWf-platelet binding in neonates.

Keywords

Neonatal and adult platelets - von Willebrand factor - flow cytometry - shear stress
 

  • References

  • 1 Rajasekhar D, Kestin AS, Bednarek FJ. et al. Neonatal platelets are less reactive than adult platelets to physiological agonists in whole blood. Thromb Haemost 1994; 72: 957-63.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 2 Israels SJ, Daniels M, McMillan EM. Deficient collagen-induced activation in the newborn platelet. Pediatr Res 1990; 27: 337-43.
    CrossrefPubMedGoogle Scholar
  • 3 Michelson AD. Platelet function in the newborn. Semin Thromb Hemost 1998; 24: 507-10.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 4 Mankin P, Maragos J, Akhand M. et al. Impaired platelet-dense granule release in neonates. J Pediatr Hematol Oncol 2000; 22: 143-7.
    CrossrefPubMedGoogle Scholar
  • 5 Israels SJ, Cheang T, Robertson C. et al. Impaired signal transduction in neonatal platelets. Pediatr Res 1999; 45: 687-91.
    CrossrefPubMedGoogle Scholar
  • 6 Gelman B, Setty BN, Chen D. et al. Impaired mobilization of intracellular calcium in neonatal platelets. Pediatr Res 1996; 39: 692-6.
    CrossrefPubMedGoogle Scholar
  • 7 Lethagen S, Kling S. New bleeding time devices with retractable blades evaluated in children, healthy volunteers and patients with prolonged bleeding time. Thromb Haemost 1993; 70: 595-7.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 8 Del Vecchio A. Use of the bleeding time in the neonatal intensive care unit. Acta Paediatr Suppl 2002; 91: 82-6.
    PubMedGoogle Scholar
  • 9 Shenkman B, Linder N, Savion N. et al. Increased neonatal platelet deposition on subendothelium under flow conditions: the role of plasma von Willebrand factor. Pediatr Res 1999; 45: 270-5.
    CrossrefPubMedGoogle Scholar
  • 10 Weinstein MJ, Blanchard R, Moake JL. et al. Fetal and neonatal von Willebrand factor (vWF) is unusually large and similar to the vWF in patients with thrombotic thrombocytopenic purpura. Br J Haematol 1989; 72: 68-72.
    CrossrefPubMedGoogle Scholar
  • 11 Thomas KB, Sutor AH, Altinkaya N. et al. Von Willebrand factor-collagen binding activity is increased in newborns and infants. Acta Paediatr 1995; 84: 697-9.
    CrossrefPubMedGoogle Scholar
  • 12 Fischer BE, Kramer G, Mitterer A. et al. Effect of multimerization of human and recombinant von Willebrand factor on platelet aggregation, binding to collagen and binding of coagulation factor VIII. Thromb Res 1996; 84: 55-66.
    CrossrefPubMedGoogle Scholar
  • 13 Tsai HM, Sarode R, Downes KA. Ultralarge von Willebrand factor multimers and normal ADAMTS13 activity in the umbilical cord blood. Thromb Res 2003; 108: 121-5.
    PubMedGoogle Scholar
  • 14 Borzini P, Lazzaro A, Mazzucco L. et al. The in-vitro bleeding time for the screening of platelet function in the newborn: assessment of a normal reference range. Eur J Pediatr 2001; 160: 199-200.
    CrossrefPubMedGoogle Scholar
  • 15 Roschitz B, Sudi K, Koestenberger M. et al. Shorter PFA-100 closure times in neonates than in adults: role of red cells, white cells, platelets and von Willebrand factor. Acta Paediatr 2001; 90: 664-70.
    PubMedGoogle Scholar
  • 16 Pareti FI, Lattuada A, Bressi C. et al. Proteolysis of von Willebrand factor and shear stress-induced platelet aggregation in patients with aortic valve stenosis. Circulation 2000; 102: 1290-5.
    CrossrefPubMedGoogle Scholar
  • 17 Michelson AD, Ellis PA, Barnard MR. et al. Downregulation of the platelet surface glycoprotein Ib-IX complex in whole blood stimulated by thrombin, adenosine diphosphate, or an in vivo wound. Blood 1991; 77: 770-9.
    PubMedGoogle Scholar
  • 18 Michelson AD. Flow cytometry: a clinical test of platelet function. Blood 1996; 87: 4925-36.
    PubMedGoogle Scholar
  • 19 Hrodek O. Blood platelets in the newborn: their function in hemostasis and hemocoagulation. Acta Univ Carolina 1966; 22: 133-44.
    PubMedGoogle Scholar
  • 20 Mull MM, Hathaway WE. Altered platelet function in newborns. Pediatr Res 1970; 04: 229-37.
    CrossrefPubMedGoogle Scholar
  • 21 Isreals SJ, Rand ML, Michelson AD. Neonatal platelet function. Semin Thromb Hemost 2003; 29: 363-72.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 22 Israels SJ, Odaibo FS, Robertson C. et al. Deficient thromboxane synthesis and response in platelets from premature infants. Pediatr Res 1997; 41: 218-23.
    PubMedGoogle Scholar
  • 23 Stuart MJ, Dusse J, Clark DA. et al. Differences in thromboxane produktion between neonatal and adult platelets in response to arachidonic acid and epinephrine. Ped Res 1984; 18: 823-6.
    CrossrefPubMedGoogle Scholar
  • 24 Corby DG, Zuck TF. Newborn platelet dysfunction: a storage pool and release defect. Thromb Haemost 1976; 36: 200-7.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 25 Ruggeri ZM. Structure and function of von Willebrand factor. Thromb Haemost 1999; 82: 576-84.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 26 Goto S, Ikeda Y, Saldivar E. et al. Distinct mechanisms of platelet aggregation as a consequence of different shearing flow conditions. J Clin Invest 1998; 101: 479-86.
    CrossrefPubMedGoogle Scholar
  • 27 Goto S, Salomon DR, Ikeda Y. et al. Characterization of the unique mechanism mediating the shear-dependent binding of soluble von Willebrand factor to platelets. J Biol Chem 1995; 270: 23352-61.
    CrossrefPubMedGoogle Scholar
  • 28 McCrary JK, Nolasco LH, Hellums JD. et al. Direct demonstration of radiolabeled von Willebrand factor binding to platelet glycoprotein Ib and IIb-IIIa in the presence of shear stress. Ann Biomed Eng 1995; 23: 787-93.
    CrossrefPubMedGoogle Scholar
  • 29 Ruggeri ZM, Ware J. The structure and function of von Willebrand factor. Thromb Haemost 1992; 67: 594-9.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 30 Furlan M. Von Willebrand factor: molecular size and functional activity. Ann Hematol 1996; 72: 341-8.
    CrossrefPubMedGoogle Scholar
  • 31 Boudewijns M, Raes M, Peeters V. et al. Evaluation of platelet function on cord blood in 80 healthy term neonates using the Platelet Function Analyser (PFA-100); shorter in vitro bleeding times in neonates than adults. Eur J Pediatr 2003; 162: 212-3.
    CrossrefPubMedGoogle Scholar
  • 32 Tsai HM, Sussman II, Nagel RL. Shear stress enhances the proteolysis of von Willebrand factor in normal plasma. Blood 1994; 83: 2171-9.
    PubMedGoogle Scholar
  • 33 Mannucci PM, Canciani MT, Forza I. et al. Changes in health and disease of the metalloprotease that cleaves von Willebrand factor. Blood 2001; 98: 2730-5.
    CrossrefPubMedGoogle Scholar