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

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)


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.


  • 1 Müller-Eckhardt C, Kiefel V, Grubert A. 348 cases of suspected neonatal alloimmune thrombocytopenia.  Lancet . 1989;  1 363-366
  • 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
  • 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
  • 4 Kaushansky K. Thrombopoietin: the primary regulator of platelet production.  Blood . 1995;  86 419-431
  • 5 Wolber E-M, Dame C, Fahnenstich H. Expression of the thrombopoietin gene in human fetal and neonatal tissues.  Blood . 1999;  94 97-105
  • 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
  • 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
  • 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
  • 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
  • 10 Du X, Williams D A. Interleukin-11: review of molecular, cell biology, and clinical use.  Blood . 1997;  89 3897-3908
  • 11 Weich N S, Wang A, Fitzgerald M. Recombinant interleukin-11 directly promotes megakaryopoiesis in vitro.  Blood . 1997;  90 3893-3902
  • 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
  • 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)
  • 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
  • 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)
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 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
  • 30 Harker L A, Finch C A. Thrombokinetics in man.  J Clin Invest . 1969;  48 963-974
  • 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
  • 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
  • 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
  • 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
  • 35 Andersson J. Cytokines in idiopathic thrombocytopenic purpura (ITP).  Acta Paediatr . 1998 (suppl 1);  424 (61-64)
  • 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)