Clinical Research Article | Published:

Impaired platelet activity and hypercoagulation in healthy term and moderately preterm newborns during the early neonatal period



Preterm newborns are at thrombohemorrhagic risk during the early neonatal period. Taking into account the lack of informative tools for the laboratory diagnosis of hemostasis disorders in newborns, our goal was to determine the baseline values of thrombodynamics and platelet functional activity in healthy term and moderately preterm newborns during the early neonatal period future potential clinical use of these tests.


Coagulation was assessed using an integral assay of thrombodynamics and standard coagulation assays, and platelet functional activity was estimated by flow cytometry.


Hypercoagulation of newborns, represented by a significantly higher clot growth velocity and the presence of spontaneous clots in the thrombodynamics, was combined with platelet hypoactivity. Granule release, phosphatidylserine exposure, and the ability to change shape upon activation were decreased in the platelets of moderately preterm newborns. The platelet function remained at the same level over the first four days of life, whereas the hypercoagulation became less pronounced.


The hemostasis of newborns is characterized by hypercoagulation combined with reduced platelet functional activity. Moderately preterm and term newborns do not differ in the parameters of coagulation, while some of the functional responses of platelets are lower in moderately preterm newborns than in term.

Access optionsAccess options

Rent or Buy article

Get time limited or full article access on ReadCube.


All prices are NET prices.

Additional information

Publisher's note: Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.


  1. 1.

    Szpecht, D., Szymankiewicz, M., Nowak, I. & Gadzinowski, J. Intraventricular hemorrhage in neonates born before 32 weeks of gestation-retrospective analysis of risk factors. Childs Nerv. Syst. 32, 1399–1404 (2016).

  2. 2.

    Bhat, R. & Monagle, P. The preterm infant with thrombosis. Arch. Dis. Child Fetal Neonatal Ed. 97, F423–F428 (2012).

  3. 3.

    Yum, S. K. et al. Risk factor profile of massive pulmonary haemorrhage in neonates: the impact on survival studied in a tertiary care centre. J. Matern. Fetal Neonatal Med. 29, 338–343 (2016).

  4. 4.

    van Elteren, H. A. et al. Management and outcome in 32 neonates with thrombotic events. Int. J. Pediatr. 2011;217564. Epub 2011 Aug 11

  5. 5.

    Tavil, B. et al. Foetal and neonatal intracranial haemorrhage in term newborn infants: Hacettepe University experience. Blood Coagul. Fibrinolysis 27, 163–168 (2016).

  6. 6.

    Ziegler, B., Solomon, C., Cadamuro, J. & Jones, N. Thromboelastometric monitoring of the hemostatic effect of platelet concentrates transfusion in thrombocytopenic children undergoing chemotherapy. Clin. Appl. Thromb. Hemost. 21, 558–564 (2015).

  7. 7.

    Deschmann, E., Sola-Visner, M. & Saxonhouse, M. A. Primary hemostasis in neonates with thrombocytopenia. J. Pediatr. 164, 167–172 (2014).

  8. 8.

    Panteleev, M. A. & Hemker, H. C. Global/integral assays in hemostasis diagnostics: promises, successes, problems and prospects. Thromb. J. 13, 5 (2015).

  9. 9.

    Gracheva, M. A. et al. Thromboelastography, thrombin generation test and thrombodynamics reveal hypercoagulability in patients with multiple myeloma. Leuk. Lymphoma 56, 3418–3425 (2015).

  10. 10.

    Seregina, E. A. et al. Laboratory tests for coagulation system monitoring in a patient with β-thalassemia. Int J. Hematol. 99, 588–596 (2014).

  11. 11.

    Sinauridze, E. I. et al. Thrombodynamics, a new global coagulation test: measurement of heparin efficiency. Talanta 180, 282–291 (2018).

  12. 12.

    Sinauridze, E. I. et al. Hypercoagulation, caused by the dilution of plasma by volume expanders. Technol. Living Syst. 5, 3–14 (2008).

  13. 13.

    Gracheva, M. A., Balandina, A. N., Ataullakhanov, F. I. & Roitman, E. V. Comparison of responses of integrated and screening tests for hemostasis assessment to various coagulation statesin models in vitro. Thromb. Haemost. Rheol. 4, 64–71 (2016).

  14. 14.

    Koltsova, E. M. et al. The laboratory control of anticoagulant thromboprophylaxis during the early postpartum period after cesarean delivery. J. Perinat. Med 46, 251–260 (2018).

  15. 15.

    Lipets, E. et al. Circulating contact-pathway-activating microparticles together with factors IXa and XIa induce spontaneous clotting in plasma of hematology and cardiologic patients. PLoS ONE 9, e87692 (2014).

  16. 16.

    Suntsova, E. V. et al. Bleeding tendency and platelet function during treatment with romiplostim in children with severe immune thrombocytopenic purpura. Int J. Hematol. 105, 1–8 (2017).

  17. 17.

    Ignatova, A. A., Karpova, O. V., Trakhtman, P. E., Rumiantsev, S. A. & Panteleev, M. A. Functional characteristics and clinical effectiveness of platelet concentrates treated with riboflavin and ultraviolet light in plasma and in platelet additive solution. Vox Sang. 110, 244–252 (2016).

  18. 18.

    Morton, L. F., Hargreaves, P. G., Farndale, R. W., Young, R. D. & Barnes, M. J. Integrin alpha 2 beta 1-independent activation of platelets by simple collagen-like peptides: collagen tertiary (triple-helical) and quaternary (polymeric) structures are sufficient alone for alpha 2 beta 1-independent platelet reactivity. Biochem. J. 306, 337–344 (1995).

  19. 19.

    Ovanesov, M. V., Ananyeva, N. M., Panteleev, M. A., Ataullakhanov, F. I. & Saenko, E. L. Initiation and propagation of coagulation from tissue factor-bearing cell monolayers to plasma: Initiator cells do not regulate spatial growth rate. J. Thromb. Haemost. 3, 321–331 (2005).

  20. 20.

    Andrew, M. et al. Development of the human coagulation system in the full-term infant. Blood 70, 165–172 (1987).

  21. 21.

    Andrew, M. et al. Development of the human coagulation system in the healthy premature infant. Blood 72, 1651–1657 (1988).

  22. 22.

    Murtha, A. P., Boggess, K. A., Jimmerson, C. E., Greig, P. C. & Herbert, W. N. Umbilical venous D-dimer concentrations with and without labor. Obstet. Gynecol. 92, 184–186 (1998).

  23. 23.

    Hudson, I. R. et al. Increased concentrations of D-dimers in newborn infants. Arch. Dis. Child 65, 383–384 (1990).

  24. 24.

    Tripodi, A. et al. Normal thrombin generation in neonates in spite of prolonged conventional coagulation tests. Haematologica 93, 1256–1259 (2008).

  25. 25.

    Sewell, E. K. et al. Thromboelastography in term neonates: an alternative approach to evaluating coagulopathy. Arch. Dis. Child Fetal Neonatal Ed. 102, F79–F84 (2017).

  26. 26.

    Kettner, S. C. et al. Heparinase-modified thrombelastography in term and preterm neonates. Anesth. Analg. 98, 1650–1652 (2004).

  27. 27.

    Tay, S. P., Cheong, S. K. & Boo, N. Y. Circulating tissue factor, tissue factor pathway inhibitor and D-dimer in umbilical cord blood of normal term neonates and adult plasma. Blood Coagul. Fibrinolysis 14, 125–129 (2003).

  28. 28.

    Soshitova, N. P. et al. Predicting prothrombotic tendencies in sepsis using spatial clot growth dynamics. Blood Coagul. Fibrinolysis 23, 498–507 (2012).

  29. 29.

    Sitaru, A. G. et al. Neonatal platelets from cord blood and peripheral blood. Platelets 16, 203–210 (2005).

  30. 30.

    Urban, D. et al. Decreased numbers of dense granules in fetal and neonatal platelets. Haematologica 102, e36–8 (2017).

  31. 31.

    Mankin, P., Maragos, J., Akhand, M. & Saving, K. L. Imparied platelet-dense granule release in neonates. J. Pediatr. Hematol. Oncol. 22, 143–147 (2000).

  32. 32.

    Del Vecchio, A., Motta, M. & Romagnoli, C. Neonatal platelet function. Clin. Perinatol. 42, 625–638 (2015).

  33. 33.

    Canpolat, F. E., Yurdakök, M., Armangil, D. & Yiit, Ş. Mean platelet volume in neonatal respiratory distress syndrome. Pediatr. Int 51, 314–316 (2009).

  34. 34.

    Wiedmeier, S. E., Henry, E., Sola-Visner, M. C. & Christensen, R. D. Platelet reference ranges for neonates, defined using data from over 47 000 patients in a multihospital healthcare system. J. Perinatol. 29, 130–136 (2009).

  35. 35.

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

  36. 36.

    Monagle, P. et al. Developmental haemostasis. Impact for clinical haemostasis laboratories. Thromb. Haemost. 95, 362–372 (2006).

  37. 37.

    Al Dieri, R. et al. The thrombogram in rare inherited coagulation disorders: Its relation to clinical bleeding. Thromb. Haemost. 88, 576–582 (2002).

  38. 38.

    Mann, K., Brummel, K. & Butenal, S. What is all that thrombin for? Thromb. Haemost. 1, 1504–1514 (2003).

  39. 39.

    Bauman, M. E., Cheung, P. Y. & Massicotte, M. P. Hemostasis and platelet dysfunction in asphyxiated neonates. J. Pediatr. 158, e35–e39 (2011).

Download references



This work was supported by a grant from the Russian Science Foundation (17-74-10224) to A.N.B.

Author information

E.M.K., E.N.B., M.A.P., and A.N.B. designed the study. E.N.B., O.V.I., A.R.K., A.A.L., L.A.T., V.V.Z., and D.N.D. recruited the participants and collected the clinical data from the participants. E.M.K. and A.D.K. performed the thrombodynamics assay, A.A.I. and D.M.P performed the platelet functional testing, and A.V.P. performed the other coagulation assays. E.M.K. performed the statistical analysis. E.M.K. wrote the manuscript, which was critically revised by A.N.B., E.N.B., and M.A.P. and finally approved by G.T.S. and F.I.A.

Competing interests

F.I.A. is former employee and founder of HemaCore LLC, which holds several patents and patent applications that are related to the diagnostic use of spatial clot growth and has developed an assay under the trade name of Thrombodynamics®.

Correspondence to Ekaterina M. Koltsova.

Electronic supplementary material

Supplementary Figures and Tables

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark
Fig. 1
Fig. 2
Fig. 3
Fig. 4