Download PDF
Am J Perinatol 2001; 18(6): 335-344
DOI: 10.1055/s-2001-17858
ORIGINAL ARTICLES

Copyright © 2001 by Thieme Medical Publishers, Inc., 333 Seventh Avenue, New York, NY 10001, USA. Tel.: +1(212) 584-4662

Concentrations of Thrombopoietin and Interleukin-11 in the Umbilical Cord Blood of Patients with Fetal Alloimmune Thrombocytopenia

Christof Dame1 , Malte Cremer1 , Matthias Ballmaier3 , Peter Bartmann1 , Rainer Bald4 , Ralf L. Schild2 , Hubert Fahnenstich5
  • 1Department of Neonatology, University of Bonn, Germany
  • 2Department of Fetal Diagnosis and Therapy, University of Bonn, Germany
  • 3Department of Pediatric Hematology and Oncology, Medical School Hannover, Germany
  • 4Department of Fetal Diagnosis and Therapy, University of Cologne, Germany
  • 5Department of Neonatology, University Children's Hospital, Basel, Switzerland
Further Information

Publication History

Publication Date:
17 October 2001 (online)

    Permissions and Reprints

ABSTRACT

The objective of this study is to determine whether the fetus compensates for fetal alloimmune thrombocytopenia (FAITP) by increasing serum concentrations of thrombopoietin (TPO) and interleukin-11 (IL-11). TPO and IL-11 concentrations were measured in cord blood sera of 12 neonates with FAITP, and 35 preterm and 25 term controls. TPO concentrations in the 12 patients (median 129 pg/mL, range 73 to 325 pg/mL) were similar to those of 35 healthy preterm neonates (median 183 pg/mL, range 71 to 290 pg/mL) and the 25 term controls (median 180 pg/mL, range 93 to 302 pg/mL), although the platelet counts were significantly lower in FAITP. TPO concentrations did not correlate with the platelet counts, platelet nadir after birth, or time to recovery of normal platelet count. IL-11 reached detectable concentrations only in four patients with FAITP (median 54 pg/mL). After birth, these patients had a more rapid recovery of the platelet count. Cord blood serum concentrations of TPO are not significantly elevated in FAITP and do not predict the severity of the thrombocytopenia. Elevated IL-11 may signal a more rapid platelet recovery in FAITP.

KEYWORD

Thrombopoietin - interleukin-11 - megakaryopoiesis - neonate

REFERENCES

  • 1 Müller-Eckhardt C, Kiefel V, Grubert A. 348 cases of suspected neonatal alloimmune thrombocytopenia.  Lancet . 1989;  1 363-366
    PubMedGoogle Scholar
  • 2 Taaning E, Skibsted L. The frequency of platelet alloantibodies in pregnant women and the occurrence and management in neonatal alloimmune thrombocytopenic purpura.  Obstet Gynecol Surv . 1990;  45 521-525
    PubMedGoogle Scholar
  • 3 Warwick R M, Vaughan J, Murray N, Lubenko A, Roberts I. In vitro culture of colony forming unit-megakaryocyte (CFU-MK) in fetal alloimmune thrombocytopenia.  Br J Haematol . 1994;  88 874-877
    PubMedGoogle Scholar
  • 4 Kaushansky K. Thrombopoietin: the primary regulator of platelet production.  Blood . 1995;  86 419-431
    PubMedGoogle Scholar
  • 5 Wolber E-M, Dame C, Fahnenstich H. Expression of the thrombopoietin gene in human fetal and neonatal tissues.  Blood . 1999;  94 97-105
    PubMedGoogle Scholar
  • 6 Fielder P J, Gurney A L, Stefanich E. Regulation of thrombopoietin levels by c-mpl-mediated binding to platelets.  Blood . 1996;  87 2154-2161
    PubMedGoogle Scholar
  • 7 Nagata Y, Shozaki Y, Nagahisa H, Nagasawa T, Abe T, Todokoro K. Serum thrombopoietin level is not regulated by transcription but by the total counts of both megakaryocytes and platelets during thrombocytopenia and thrombocytosis.  Thromb Haemost . 1997;  77 808-814
    PubMedGoogle Scholar
  • 8 Stoffel R, Wiestner A, Skoda R C. Thrombopoietin in thrombocytopenic mice: evidence against regulation at the mRNA level and for a direct regulatory role of platelets.  Blood . 1996;  87 567-573
    PubMedGoogle Scholar
  • 9 Sungaran R, Chisholm O T, Markovic B, Khachigian L M, Tanaka Y, Chong B H. The role of platelet alpha-granular proteins in the regulation of thrombopoietin messenger RNA expression in human bone marrow stromal cells.  Blood . 2000;  95 3094-3101
    PubMedGoogle Scholar
  • 10 Du X, Williams D A. Interleukin-11: review of molecular, cell biology, and clinical use.  Blood . 1997;  89 3897-3908
    PubMedGoogle Scholar
  • 11 Weich N S, Wang A, Fitzgerald M. Recombinant interleukin-11 directly promotes megakaryopoiesis in vitro.  Blood . 1997;  90 3893-3902
    PubMedGoogle Scholar
  • 12 Broudy V C, Lin N L, Kaushansky K. Thrombopoietin (c-mpl ligand) acts synergistically with erythropoietin, stem cell factor, and interleukin-11 to enhance murine megakaryocyte colony growth and increases megakaryocyte ploidy in vitro.  Blood . 1995;  85 1719-1726
    PubMedGoogle Scholar
  • 13 Wu X, Adamson J W. Interleukin (IL)-11 upregulates thrombopoietin (Tpo) gene expression and Tpo release by the human stromal cell line, HS27A.  Blood . 2000 (suppl 1/2);  96 (541b)
    PubMedGoogle Scholar
  • 14 Mandelbrot L, Daffos F, Forestier F, MacAleese J, Descombey D. Assessment of fetal blood volume for computer assisted management of in utero transfusion.  Fetal Ther . 1988;  3 60-66
    PubMedGoogle Scholar
  • 15 Dame C, Fahnenstich H, Schaaff F, Schild R L, Bartmann P. Longitudinal determinations of fetal thrombopoietin concentrations in severe Rhesus hemolytic disease.  Pediatr Res . 2000 (suppl 2);  47 (332A)
    PubMedGoogle Scholar
  • 16 Murray N A, Watts T L, Roberts I AG. Endogenous thrombopoietin levels and effect of recombinant human thrombopoietin on megakaryocyte precursors in term and preterm babies.  Pediatr Res . 1998;  43 148-151
    PubMedGoogle Scholar
  • 17 Sainio S, Javela K, Kekomäki R, Teramo K. Thrombopoietin levels in cord blood plasma and amniotic fluid in fetuses with alloimmune thrombocytopenia and healthy controls.  Br J Haematol . 2000;  109 330-335
    CrossrefPubMedGoogle Scholar
  • 18 Walka M M, Sonntag J, Dudenhausen J W, Obladen M. Thrombopoietin concentration in umbilical cord blood of healthy term newborns is higher than in adult controls.  Biol Neonate . 1999;  75 54-58
    CrossrefPubMedGoogle Scholar
  • 19 Watts T L, Murray N A, Roberts I AG. Thrombopoietin has a primary role in the regulation of platelet production in preterm babies.  Pediatr Res . 1999;  46 28-32
    PubMedGoogle Scholar
  • 20 Albert T SE, Meng G, Simms P, Cohen R L, Phibbs R H. Thrombopoietin in the thrombocytopenic term and preterm newborn.  Pediatrics . 2000;  105 1286-1291
    CrossrefPubMedGoogle Scholar
  • 21 Sola M C, Calhoun D A, Hutson A D, Christensen R D. Plasma thrombopoietin concentrations in thrombocytopenic and non-thrombocytopenic patients in a neonatal intensive care unit.  Br J Haematol . 1999;  104 90-92
    CrossrefPubMedGoogle Scholar
  • 22 Sola M C, Juul S E, Meng Y G. Thrombopoietin (Tpo) in the fetus and neonate: Tpo concentrations in preterm and term neonates, and organ distribution of Tpo and its receptor (c-mpl) during human fetal development.  Early Hum Dev . 1999;  53 239-250
    CrossrefPubMedGoogle Scholar
  • 23 Ishiguro A, Nakahata T, Matsubara K. Age-related changes in thrombopoietin in children: reference interval for serum thrombopoietin levels.  Br J Haematol . 1999;  106 884-888
    CrossrefPubMedGoogle Scholar
  • 24 Kuter D J, Rosenberg R D. The reciprocal relationship of thrombopoietin (c-mpl ligand) to changes in the platelet mass during busulfan-induced thrombocytopenia in the rabbit.  Blood . 1995;  85 2720-2730
    PubMedGoogle Scholar
  • 25 Folman C C, von dem Borne E A, Rensink I H. Sensitive measurement of thrombopoietin by a monoclonal antibody based sandwich enzyme-linked immunosorbent assay.  Thromb Haemost . 1997;  78 1262-1267
    PubMedGoogle Scholar
  • 26 Möller P, Andersson P O, Andersson A C, Wadenvik H. Plasma thrombopoietin concentrations in response to platelet transfusion therapy.  Acta Haematol . 1999;  102 131-134
    CrossrefPubMedGoogle Scholar
  • 27 Weisdorf D J, DeFor T, Nichol J, Panoskaltsis-Mortai A, Blazar B R. Thrombopoietic cytokines in relation to platelet recovery after bone marrow transplantation.  Bone Marrow Transplant . 2000;  25 711-715
    CrossrefPubMedGoogle Scholar
  • 28 Chang M, Suen Y, Meng G. Differential mechanisms in the regulation of endogenous levels of thrombopoietin and interleukin-11 during thrombocytopenia: insight into the regulation of platelet production.  Blood . 1996;  88 3354-3362
    PubMedGoogle Scholar
  • 29 Emmons R VB, Reid D M, Cohen R L. Human thrombopoietin levels are high when thrombocytopenia is due to megakaryocyte deficiency and low when due to increased platelet destruction.  Blood . 1996;  87 4068-4071
    PubMedGoogle Scholar
  • 30 Harker L A, Finch C A. Thrombokinetics in man.  J Clin Invest . 1969;  48 963-974
    PubMedGoogle Scholar
  • 31 Cremer M, Schulze H, Linthorst G. Serum levels of thrombopoietin, IL-11, and IL-6 in pediatric thrombocytopenias.  Ann Hematol . 1999;  78 401-407
    CrossrefPubMedGoogle Scholar
  • 32 Nichol J L. Serum levels of thrombopoietin in health and disease. In: Kuter DJ, Hunt P, Sheridan W, Zucker-Franklin D, eds. Thrombopoiesis and Thrombopoietins: Molecular, Cellular, Preclinical, and Clinical Biology Totowa, NJ: Humana Press 1997: 359-375
    Google Scholar
  • 33 Bruno E, Briddell R A, Cooper R J, Hoffman R. Effects of recombinant interleukin-11 on human megakaryocyte progenitor cells.  Exp Hematol . 1991;  9 378-381
    PubMedGoogle Scholar
  • 34 Barton B E, Shortall J, Jackson J V. Interleukins 6 and 11 protect mice from mortality in a staphylococcal enterotoxin-induced toxic shock model.  Infect Immun . 1996;  64 714-718
    PubMedGoogle Scholar
  • 35 Andersson J. Cytokines in idiopathic thrombocytopenic purpura (ITP).  Acta Paediatr . 1998 (suppl 1);  424 (61-64)
    PubMedGoogle Scholar
  • 36 Wu X, Boccone L. Interleukine-11 (IL-11) administration upregulates thrombopoietin (Tpo) gene expression in mouse bone marrow.  Blood . 1998 (suppl 1);  92 (64a)
    PubMedGoogle Scholar
      >