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Thromb Haemost 1999; 81(06): 906-909
DOI: 10.1055/s-0037-1614596
Letters to the Editor
Schattauer GmbH

High Levels of Circulating Thrombomodulin in Human Foetuses and Children

Suzanne Menashi
4   From U353 INSERM, Hôpital Saint Louis, Paris
,
Marie-Hélène Aurousseau
1   Laboratoire d’Hématologie, Hôpital Jean Verdier, Bondy
,
Danielle Gozin
4   From U353 INSERM, Hôpital Saint Louis, Paris
,
Fernand Daffos
2   Service de Médecine et de Biologie Foetales, Institut de Puériculture, Paris, France
,
Armando D’Angelo
3   Service di Coagulazione, IRCCS H S Rafaele, Milano, Italy
,
François Forestier
2   Service de Médecine et de Biologie Foetales, Institut de Puériculture, Paris, France
,
Marie-Claire Boffa
› Author Affiliations
Further Information

Publication History

Received 31 December 1998

Accepted after revision 08 March 1999

Publication Date:
09 December 2017 (online)

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Summary

Thrombomodulin (TM) is an endothelial cell surface proteoglycan with anticoagulant functions, also implicated in cell proliferation, cell-cell adhesion and differentiation. In this study we determined circulating plasma TM (pTM) levels in human foetuses at different stages of pregnancy, at birth and in childhood. TM levels increased with gestational age, the median level reaching a peak of approximately 165 ng/ml between the 23rd and 26th week, thereafter decreasing gradually, reaching a value of 108 ng/ml at birth. pTM continues to decrease progressively during childhood, reaching in the 5-15 years group a median of 56 ng/ml which approaches the adult value. The pTM peak was statistically significant and represents a specific foetal phenomenon as it was independent of the corresponding maternal values. As a whole, the pTM pattern during foetal maturation appears totally different from that of protein C, prothrombin and other coagulation activators and inhibitors and thus, TM may play in the foetus another role in addition to its well-known anticoagulant function.

 

  • References

  • 1 Esmon CT. Thrombomodulin as a model of molecular mechanisms that modulate protease specificity and function at the vessel surface. FASEB J 1995; 9: 946-55.
    CrossrefPubMedGoogle Scholar
  • 2 Sadler JE. Thrombomodulin structure and function. Thromb Haemost 1997; 78: 392-5.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 3 Bajzar L, Morser J, Nesheim M. TAFI, or plasma procarboxypeptidase B, couples the coagulation and fibrinolytic cascades through the thrombinthrombomodulin complex. J Biol Chem 1996; 271: 16603-8.
    CrossrefPubMedGoogle Scholar
  • 4 Lafay M, Laguna R, Le Bonniec BF, Lasne D, Aiach M, Rendu F. Thrombomodulin modulates the mitogenic response to thrombin of human umbilical vein endothelial cells. Thromb Haemost 1998; 79: 848-52.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 5 Zhang Y, Weiler-Guettler H, Chen J, Wilhelm O, Deng Y, Qiu F, Nakagawa K, Klevesath M, Wilhelm S, Bôhrer H, Nakagawa M, Graeff EMartin, Stern DM, Rosenberg RD, Ziegler R, Nawroth PP. Thrombomodulin modulates growth of tumor cells independent of its anticoagulant activity. J Clin Invest 1998; 101: 1301-9.
    CrossrefPubMedGoogle Scholar
  • 6 Mizutani H, Hayashi T, Nouchi N, Ohyanagi S, Hashimoto K, Shimizu M, Suzuki K. Functional and immunoreactive thrombomodulin expressed by keratinocytes. J Invest Dermatol 1994; 103: 825-8.
    CrossrefPubMedGoogle Scholar
  • 7 Raife TJ, Lager DJ, Madison KC, Piette WW, Howard EJ, Sturm MT, Chen Y, Lentz SR. Thrombomodulin expression by human keratinocytes. Induction of cofactor activity during epidermal differentiation. J Clin Invest 1994; 93: 1846-51.
    CrossrefPubMedGoogle Scholar
  • 8 Senet P, Peyri N, Berard M, Dubertret L, Boffa MC. Thrombomodulin, a functional surface protein on human keratinocytes, is regulated by retinoic acid. Arch Dermatol 1997; 289: 151-7.
    CrossrefPubMedGoogle Scholar
  • 9 Matsushita Y, Yoshiie K, Imamura Y, Ogawa H, Imamura H, Takao S, Yonezawa S, Aikou T, Maruyama I, Sato E. A subcloned human esophageal squamous cell carcinoma cell line with low thrombomodulin expression showed increased invasiveness compared with a high thrombomodulin expressing clone-thrombomodulin as a possible candidate for an adhesion molecule of squamous cell carcinoma. Cancer Lett 1998; 127: 195-201.
    CrossrefPubMedGoogle Scholar
  • 10 Rosenberg RD. The absence of the blood clotting regulator thrombomodulin causes embryonic lethality in mice before development of a functional cardiovascular system. Thromb Haemost 1995; 74: 52-7.
    PubMedGoogle Scholar
  • 11 Imada M, Imada S, Iwasaki H, Kume A, Yamaguchi H, Moore EE. Fetomodulin: marker surface protein of fetal development which is modulatable by cyclic AMP. Dev Biol 1987; 122: 483-91.
    CrossrefPubMedGoogle Scholar
  • 12 Imada S, Yamaguchi H, Nagumo M, Katayanagi S, Iwasaki H, Imada M. Identification of fetomodulin, a surface marker protein of fetal development, as thrombomodulin by gene cloning and functional assays. Dev Biol 1990; 140: 113-22.
    CrossrefPubMedGoogle Scholar
  • 13 Forestier F, Daffos F, Rainaut M, Solé Y, Amiral J. Vitamin K dependent proteins in fetal hemostasis at mid trimester of pregnancy. Thromb Haemost 1985; 53: 401-3.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 14 Reverdiau-Moalic P, Delahousse B, Body G, Bardos P, Leroy J, Gruel Y. Evolution of blood coagulation activators and inhibitors in the healthy human fetus. Blood 1996; 88: 900-6.
    PubMedGoogle Scholar
  • 15 Maruyama I, Bell CE, Majerus PW. Thrombomodulin is found on endothelium of arteries, veins, capillaries, and lymphatics, and on syncytiotrophoblast of human placenta. J Cell Biol 1985; 101: 363-71.
    CrossrefPubMedGoogle Scholar
  • 16 Ishii H, Majerus PW. Thrombomodulin is present in human plasma and urine. J Clin Invest 1985; 76: 2178-81.
    CrossrefPubMedGoogle Scholar
  • 17 Boffa MC. Considering cellular thrombomodulin distribution and its modulating factors can facilitate the use of plasma thrombomodulin as a reliable endothelial marker. Haemostasis 1996; 26 (Suppl. 04) 233-43.
    PubMedGoogle Scholar
  • 18 Amiral J, Adam M, Mimilla F, Larrivaz I, Chambrette B, Boffa MC. Design and validation of a new immunoassay for soluble forms of thrombomodulin and studies on plasma. Hybridoma 1994; 13: 205-13.
    CrossrefPubMedGoogle Scholar
  • 19 Tanaka A, Ishii H, Hiraishi S, Kazama M, Maezawa H. Increased thrombomodulin values in plasma of diabetic men with microangiopathy. Clin Chem 1991; 37: 269-72.
    PubMedGoogle Scholar
  • 20 Gando S, Kameue T, Nanzaki S, Nakanishi Y. Cytokines, soluble thrombomodulin and disseminated intravascular coagulation in patients with systemic inflammatory response syndrome. Thromb Res 1995; 80: 519-26.
    CrossrefPubMedGoogle Scholar
  • 21 Wada H, Ohiwa M, Kaneko T, Tamaki S, Tanigawa M, Shirakawa S, Koyama M, Hayashi T, Suzuki K. Plasma thrombomodulin as a marker of vascular disorders in thrombotic thrombocytopenic purpura and disseminated intravascular coagulation. Am J Hematol 1992; 39: 20-4.
    CrossrefPubMedGoogle Scholar
  • 22 Takano S, Kimura S, Ohdama S, Aoki N. Plasma thrombomodulin in health and diseases. Blood 1990; 76: 2024-9.
    PubMedGoogle Scholar
  • 23 Daffos F, Capella-Pavlovski M, Forestier F. Fetal blood sampling during pregnancy with needle guided by ultrasound. A study of 66 consecutive cases. Am J Obstet Gynecol 1985; 153: 655-60.
    CrossrefPubMedGoogle Scholar
  • 24 Nako Y, Tomomasa T, Morikawa A. Plasma thrombomodulin level in newborn infants with and without perinatal asphyxia. Acta Paediatr 1997; 86: 91-5.
    CrossrefPubMedGoogle Scholar
  • 25 Yurdakok M, Yigit S. Plasma thrombomodulin, plasminogen activator and plasminogen activator inhibitor levels in preterm infants with or without respiratory distress syndrome. Acta Pediatr 1977; 86: 1022-3.
    PubMedGoogle Scholar
  • 26 Nako Y, Ohki Y, Harigaya A, Tomomasa T, Morikawa A. Plasma thrombomodulin level in very low birthweight infants at birth. Acta Paediatr 1997; 86: 1105-9.
    CrossrefPubMedGoogle Scholar
  • 27 De Moerloose P, Mermillod N, Amiral J, Reber G. Thrombomodulin levels during normal pregnancy, at delivery and in postpartum: comparison with tissue-type plasminogen activator and plasminogen activator inhibitor-1. Thromb Haemost 1998; 79: 554-6.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 28 Boffa MC, Valsecchi L, Fausto A, Gozin D, Vigano’D’Angelo S, Safa O, Castiglioni MT, Amiral J, D’Angelo A. Predictive value of plasma thrombomodulin in preeclampsia and gestational hypertension. Thromb Haemost 1998; 79: 1092-5.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 29 Andrew M, Vegh P, Johnston M, Bowker J, Ofosu F, Mitchell L. Maturation of the hemostatic system during childhood. Blood 1992; 80: 1998-2005.
    CrossrefPubMedGoogle Scholar
  • 30 Ries M, Klinge J, Rauch R. Age-related reference values for activation markers of the coagulation and fibrinolytic systems in children. Thromb Res 1997; 85: 341-4.
    CrossrefPubMedGoogle Scholar
  • 31 Soifer SJ, Peters KG, O’Keefe J, Coughlin SR. Disparate temporal expression of the prothrombin and thrombin receptor genes during mouse development. Am J Path 1993; 144: 60-9.
    PubMedGoogle Scholar