Thromb Haemost 2010; 103(05): 1016-1021
DOI: 10.1160/TH09-03-0148
Platelets and Blood Cells
Schattauer GmbH

Immature platelet values indicate impaired megakaryopoietic activity in neonatal early-onset thrombocytopenia

Malte Cremer*
1   Department of Neonatology, Charité – Universitätsmedizin Berlin, Berlin, Germany
,
Andreas Weimann*
2   Central Institute for Laboratory Medicine and Pathobiochemistry, Charité – Universitätsmedizin Berlin, Berlin, Germany
,
Hannes Hammer
1   Department of Neonatology, Charité – Universitätsmedizin Berlin, Berlin, Germany
,
Christoph Bührer
1   Department of Neonatology, Charité – Universitätsmedizin Berlin, Berlin, Germany
,
Christof Dame
1   Department of Neonatology, Charité – Universitätsmedizin Berlin, Berlin, Germany
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Publikationsverlauf

Received: 06. März 2009

Accepted after major revision: 05. Januar 2010

Publikationsdatum:
22. November 2017 (online)

Summary

Newly released platelets, referred to as immature platelets, can be reliably quantified based on their RNA content by flow cytometry in an automated blood analyser. The absolute number of immature platelets (IPF#) and the immature platelet fraction (IPF%) reflect megakaryopoietic activity. We aimed to analyse the implication of these parameters in analysing the pathomechanism of early-onset neonatal thrombocytopenia. Platelet counts and IPF were determined at day 1 to 3 (d1 to d3) in 857 neonates admitted to intensive care. In thrombocytopenic patients (platelet counts<150 x 109/l, n=129), IPF# was significantly lower (8.5 ± 2.7 x 109/l), than in non-thrombocytopenic neonates (9.5 ± 3.6 x 109/l, n=682, p<0.05). IPF% was significantly higher in thrombocytopenic (9.3 ± 7.9%) vs. non-thrombocytopenic neonates (4.1 ± 1.8%, p<0.001). While neonates with early-onset infection (n=134) had lower platelet counts (199 ± 75 x 109/l) compared to controls (230 ± 68 x 109/l, n=574, p<0.01), there were no differences in IPF# or IPF%. Likewise, “small for gestational age” infants (SGA, n=149) had lower platelet counts at d1 (199 ± 75 x 109/l, p<0.001) than controls, but no differences in IPF. A trend towards lower IPF# was detected if SGA infants with platelet counts <100 x 109/l (5.4 ± 3.9 x 109/l, n=11) and thrombocytopenic neonates with infection (9.9 ± 7.3 x 109/l, n=10, p=0.11) were compared. The evaluation of IPF# indicates that thrombocytopenia in neonates is likely due to a combination of increased platelet consumption and inadequate megakaryopoietic response by the neonatal bone marrow. Furthermore, SGA neonates with moderate and severe thrombocytopenia might have a pronounced suppression of megakaryopoiesis compared to neonates with infection.

* These authors contributed equally to the study.


 
  • References

  • 1 Castle V, Andrew M, Kelton J. et al. Frequency and mechanism of neonatal thrombocytopenia. J Pediatr 1986; 108: 749-755.
  • 2 Mehta P, Vasa R, Neumann L. et al. Thrombocytopenia in the high-risk infant. J Pediatr 1980; 97: 791-794.
  • 3 Christensen RD, Henry E, Wiedmeier SE. et al. Thrombocytopenia among extremely low birth weight neonates: data from a multihospital healthcare system. J Perinatol 2006; 26: 348-353.
  • 4 Sola-Visner M, Saxonhouse MA, Brown RE. Neonatal thrombocytopenia: what we do and don‘t know. Early Hum Dev 2008; 84: 499-506.
  • 5 Ingram M, Coopersmith A. Reticulated platelets following acute blood loss. Br J Haematol 1969; 17: 225-229.
  • 6 Kienast J, Schmitz G. Flow cytometric analysis of thiazole orange uptake by platelets: a diagnostic aid in the evaluation of thrombocytopenic disorders. Blood 1990; 75: 116-121.
  • 7 Peterec SM, Brennan SA, Rinder HM. et al. Reticulated platelet values in normal and thrombocytopenic neonates. J Pediatr 1996; 129: 269-274.
  • 8 Briggs C, Kunka S, Hart D. et al. Assessment of an immature platelet fraction (IPF) in peripheral thrombocytopenia. Brit J Haematol 2004; 126: 93-99.
  • 9 Lerkevang GE, Hvas AM, Dalby KS. Immature platelets in patients with acute coronary syndromes. Thromb Haemost 2009; 101: 151-156.
  • 10 Takami A, Shibayama M, Orito M. et al. Immature platelet fraction for prediction of platelet engraftment after allogeneic stem cell transplantation. Bone Marrow Transplant 2007; 39: 501-507.
  • 11 Zucker ML, Murphy CA, Rachel JM. et al. Immature platelet fraction as a predictor of platelet recovery following hematopoietic progenitor cell transplantation. Lab Hematol 2006; 12: 125-130.
  • 12 Briggs C, Hart D, Kunka S. et al. Immature platelet fraction measurement: a future guide to platelet transfusion requirement after haematopoietic stem cell transplantation. Transfusion Med 2006; 16: 101-109.
  • 13 Abe Y, Wada H, Tomatsu H. et al. A simple technique to determine thrombopoiesis level using immature platelet fraction (IPF). Thromb Res 2006; 118: 463-469.
  • 14 Cremer M, Paetzold J, Schmalisch G. et al. Immature platelet fraction as novel lab-oratory parameter predicting the course of neonatal thrombocytopenia. Brit J Haematol 2009; 144: 619-621.
  • 15 Brown RE, Rimsza LM, Pastos K. et al. Effects of sepsis on neonatal thrombopoiesis. Pediatr Res 2008; 64: 399-404.
  • 16 Murray NA, Roberts IA. Circulating megakaryocytes and their progenitors in early thrombocytopenia in preterm neonates. Pediatr Res 1996; 40: 112-119.
  • 17 Sola MC, Calhoun DA, Hutson AD. et al. Plasma thrombopoietin concentrations in thrombocytopenic and non-thrombocytopenic patients in a neonatal intensive care unit. Brit J Haematol 1999; 104: 90-92.
  • 18 Albanyan A, Murphy MF, Wilcock M. et al. Changes in the immature platelet fraction within ageing platelet concentrates. J Thromb Haemost 2008; 06: 2213-2215.
  • 19 Saxonhouse MA, Sola MC, Pastos KM. et al. Reticulated platelet percentages in term and preterm neonates. J Pediatr Hematol Oncol 2004; 26: 797-802.
  • 20 Joseph MA, Adams D, Maragos J. et al. Flow cytometry of neonatal platelet RNA. J Pediat Hematol Onc 1996; 18: 277-281.
  • 21 Cremer M, Dame C, Schaeffer HJ. et al. Longitudinal thrombopoietin plasma concentrations in fetuses with alloimmune thrombocytopenia treated with intrauterine PLT transfusions. Transfusion 2003; 43: 1216-1222.
  • 22 Dame C, Cremer M, Ballmaier M. et al. Concentrations of thrombopoietin and interleukin-11 in the umbilical cord blood of patients with fetal alloimmune thrombocytopenia. Am J Perinatol 2001; 18: 335-344.
  • 23 Dame C. Developmental biology of thrombopoietin in the human fetus and neonate. Acta Paediatr Suppl 2002; 91: 54-65.
  • 24 Murray NA, Watts TL, Roberts IA. Endogenous thrombopoietin levels and effect of recombinant human thrombopoietin on megakaryocyte precursors in term and preterm babies. Pediatr Res 1998; 43: 148-151.
  • 25 Watts TL, Murray NA, Roberts IA. Thrombopoietin has a primary role in the regulation of platelet production in preterm babies. Pediatr Res 1999; 46: 28-32.
  • 26 Meberg A. Transitory thrombocytopenia in newborn mice after intrauterine hypoxia. Pediatr Res 1980; 14: 1071-1073.