Collagen/Endogenous Thrombin-Induced Platelet Aggregation in Cord versus Adult Whole Blood

Background: In previous studies, neonatal platelets have been shown to be hypoaggregable to various agonists when compared with adult platelets. Objectives: It was the aim of this study to investigate the aggregability of neonatal versus adult platelets when the physiological relevant agonist collagen/endogenous thrombin is used. Methods and Results: Whole blood (WB) aggregation experiments employing the impedance method revealed the same responsiveness of neonatal and adult platelets to collagen/endogenous thrombin. Maximum aggregation (13.5 ± 3.2 vs. 13.6 ± 3.2 Ω; p = 0.94), slope (5.8 ± 1.8 vs. 6.2 ± 2.6 Ω/min; p = 0.79) and lag time until the onset of platelet aggregation (38.7 ± 8.9 vs. 42.6 ± 16.5 s; p = 0.59) were similar in cord and adult WB. However, the rise in serotonin plasma levels due to platelet activation was significantly lower in neonates versus adults (227.57 ± 57.65 vs. 473.34 ± 155.75 ng/ml; p = 0.0001). Furthermore, we found a fast capability of cord plasma to generate (the efficient platelet agonist) endogenous thrombin: thrombin generation started significantly earlier in cord compared with adult plasma (215 ± 19 vs. 247 ± 21 s; p = 0.01). Moreover, thrombelastometry revealed significantly shorter coagulation times in cord versus adult WB activated with collagen/endogenous thrombin (229.8 ± 12.5 vs. 256.3 ± 25.3 s; p = 0.003). Conclusions: The efficient platelet aggregation in cord WB provoked by collagen/endogenous thrombin might help to explain the clinically observed well-functioning primary hemostasis of neonates.

[1]  M. Koestenberger,et al.  Collagen/endogenous thrombin-induced platelet aggregation in whole blood samples , 2007, Blood coagulation & fibrinolysis : an international journal in haemostasis and thrombosis.

[2]  M. Koestenberger,et al.  Effects of β2-glycoprotein-I on platelet aggregation in cord versus adult whole blood , 2007, Platelets.

[3]  T. Lindahl,et al.  Evaluation of platelet function, a method comparison , 2006, Platelets.

[4]  Dougald M Monroe,et al.  What does it take to make the perfect clot? , 2006, Arteriosclerosis, thrombosis, and vascular biology.

[5]  C. Male,et al.  Protein S modulates the anticoagulant action of recombinant human activated protein C: a comparison between neonates and adults , 2005, British journal of pharmacology.

[6]  J. Weitz,et al.  Pharmacology and clinical potential of direct thrombin inhibitors. , 2005, Current pharmaceutical design.

[7]  A. Newman-Tancredi,et al.  Contrasting Contribution of 5-Hydroxytryptamine 1A Receptor Activation to Neurochemical Profile of Novel Antipsychotics: Frontocortical Dopamine and Hippocampal Serotonin Release in Rat Brain , 2005, Journal of Pharmacology and Experimental Therapeutics.

[8]  J. Heemskerk,et al.  Synergistic Effect of Thrombin on Collagen-Induced Platelet Procoagulant Activity Is Mediated Through Protease-Activated Receptor-1 , 2005, Arteriosclerosis, thrombosis, and vascular biology.

[9]  S. Kemahlı,et al.  PLATELET AGGREGATION IN TERM AND PRETERM NEWBORNS , 2005, Pediatric hematology and oncology.

[10]  V. Ribitsch,et al.  Increased shear stress- and ristocetin-induced binding of von Willebrand factor to platelets in cord compared with adult plasma , 2004, Thrombosis and Haemostasis.

[11]  W. Muntean,et al.  Elevated thrombin‐forming capacity of tissue factor‐activated cord compared with adult plasma , 2003, Journal of thrombosis and haemostasis : JTH.

[12]  J. Ingerslev,et al.  Whole blood coagulation thrombelastographic profiles employing minimal tissue factor activation , 2003, Journal of thrombosis and haemostasis : JTH.

[13]  W. Muntean,et al.  Low tissue factor pathway inhibitor (TFPI) together with low antithrombin allows sufficient thrombin generation in neonates , 2003, Journal of thrombosis and haemostasis : JTH.

[14]  B. Engelmann,et al.  Intravascular tissue factor pathway – a model for rapid initiation of coagulation within the blood vessel , 2003, Thrombosis and Haemostasis.

[15]  A. Vecchio.  Use of the bleeding time in the neonatal intensive care unit , 2002 .

[16]  A. Del Vecchio.  Use of the bleeding time in the neonatal intensive care unit. , 2002, Acta paediatrica (Oslo, Norway : 1992). Supplement.

[17]  A. Hutson,et al.  The Relationship Between Hematocrit and Bleeding Time in Very Low Birth Weight Infants During the First Week of Life , 2001, Journal of Perinatology.

[18]  K. Saving,et al.  Imparied platelet--dense granule release in neonates. , 2000, Journal of pediatric hematology/oncology.

[19]  K. Mann,et al.  "Normal" thrombin generation. , 1999, Blood.

[20]  S. Israels,et al.  Impaired Signal Transduction in Neonatal Platelets , 1999, Pediatric Research.

[21]  H. Hemker,et al.  Prevention of the influence of fibrin and alpha2-macroglobulin in the continuous measurement of the thrombin potential: implications for an endpoint determination of the optical density. , 1998, Thrombosis research.

[22]  A. Michelson.  Platelet function in the newborn. , 1998, Seminars in thrombosis and hemostasis.

[23]  R. Knöfler,et al.  Platelet Function Tests in Childhood. Measuring Aggregation and Release Reaction in Whole Blood , 1998, Seminars in thrombosis and hemostasis.

[24]  F. Dorner,et al.  Effect of multimerization of human and recombinant von Willebrand factor on platelet aggregation, binding to collagen and binding of coagulation factor VIII. , 1996, Thrombosis research.

[25]  A. Grohmann,et al.  von Willebrand factor‐collagen binding activity is increased in newborns and infants , 1995, Acta paediatrica.

[26]  A. Michelson,et al.  Neonatal Platelets Are Less Reactive than Adult Platelets to Physiological Agonists in Whole Blood , 1994, Thrombosis and Haemostasis.

[27]  S. Lethagen,et al.  New Bleeding Time Devices with Retractable Blades Evaluated in Children, Healthy Volunteers and Patients with Prolonged Bleeding Time , 1993, Thrombosis and Haemostasis.

[28]  H. Hemker,et al.  Continuous Registration of Thrombin Generation in Plasma, Its Use for the Determination of the Thrombin Potential , 1993, Thrombosis and Haemostasis.

[29]  S. Israels,et al.  Deficient Collagen-Induced Activation in the Newborn Platelet , 1990, Pediatric Research.

[30]  P. Powers,et al.  Development of the human coagulation system in the full-term infant. , 1987, Blood.

[31]  D. Cohen,et al.  Determination of serotonin in whole blood, platelet-rich plasma, platelet-poor plasma and plasma ultrafiltrate. , 1987, Life sciences.

[32]  H. Hemker,et al.  A Computer Assisted Method to Obtain the Prothrombin Activation Velocity in Whole Plasma Independent of Thrombin Decay Processes , 1986, Thrombosis and Haemostasis.

[33]  H. Hemker,et al.  On the procoagulant activity of platelets stimulated by collagen and thrombin. , 1984, Thrombosis Research.

[34]  R. Heethaar,et al.  Red blood cell size is important for adherence of blood platelets to artery subendothelium. , 1983, Blood.

[35]  E. Plow,et al.  Inhibition of fibrinogen binding to human platelets by the tetrapeptide glycyl-L-prolyl-L-arginyl-L-proline. , 1982, Proceedings of the National Academy of Sciences of the United States of America.