Download PDF
Thromb Haemost 1998; 79(06): 1092-1095
DOI: 10.1055/s-0037-1615021
Rapid Communication
Schattauer GmbH

Predictive Value of Plasma Thrombomodulin in Preeclampsia and Gestational Hypertension

Marie-Claire Boffa
1   From the INSERM Unité 353, Hôpital Saint-Louis, Paris, France
,
Luca Valsecchi
2   From the Cattedra di Ostetricia e Ginecologia, Milano, Italy
,
Alfonso Fausto
2   From the Cattedra di Ostetricia e Ginecologia, Milano, Italy
,
Danielle Gozin
1   From the INSERM Unité 353, Hôpital Saint-Louis, Paris, France
,
Silvana Vigano’ D’Angelo
3   From the Servizio di Coagulazione, Istituto Scientifico H S. Raffaele, Milano, Italy
,
Omid Safa
3   From the Servizio di Coagulazione, Istituto Scientifico H S. Raffaele, Milano, Italy
,
Maria Teresa Castiglioni
2   From the Cattedra di Ostetricia e Ginecologia, Milano, Italy
,
Jean Amiral
4   From the Serbio, Gennevilliers, France
,
Armando D’Angelo
3   From the Servizio di Coagulazione, Istituto Scientifico H S. Raffaele, Milano, Italy
› Author Affiliations
Further Information

Publication History

Received 16 July 1997

Accepted after resubmission 04 February 1998

Publication Date:
07 December 2017 (online)

Also available at
    Permissions and Reprints

Summary

In a prospective longitudinal study, 130 primigravidae at risk for preeclampsia were examined and plasma sampling performed in 45 of them. Plasma thrombomodulin (pTM) was sequentially measured at weeks 12, 24 and 32 of gestation and after delivery in 20 primigravidae who developed either mild preeclampsia (n = 8) or gestational hyper-tension (n = 12) between weeks 32 and 39 of gestation and in 25 (age-matched) primigravidae who had uneventful pregnancies. pTM elevations were not observed until week 32 in uneventful pregnancies, but were present by week 24 (p = 0.002) in patients who later developed hypertensive complications. A net individual pTM increase ≥4.2 ng/ml between weeks 12 and 24 (more than 8 times that of normotensive primigravidae) and/or pTM level ≥47.5 ng/ml at week 32 predicted the development of hypertensive complications with 80% accuracy. Serial pTM determinations can be useful to select pregnancies who may benefit from early pharmacological intervention.

 

  • References

  • 1 Aznar J, Gilalbert J, Estellés A, España F. Fibrinolytic activity and protein C in preeclampsia.. Thromb Haemost 1986; 55: 314-7.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 2 Perry KG, Martin Jr. JN. Abnormal hemostasis and coagulopathy in preeclampsia and eclampsia.. Clin Obstet Gynecol 1992; 35: 338-50.
    CrossrefPubMedGoogle Scholar
  • 3 Hustin J, Foldart JM, Lambotte R. Maternal vascular lesions in preeclampsia and intrauterine growth retardation: light microscopy and immunofluorescence.. Obstet Gynecol Survey 1985; 40: 145-9.
    CrossrefPubMedGoogle Scholar
  • 4 Esmon CT, Schwarz HP. An update on clinical and basic aspects of the protein C anticoagulant pathway.. Trends Cardiovasc Med 1995; 5: 141-8.
    CrossrefPubMedGoogle Scholar
  • 5 Maruyama I, Bell CE, Majerus PW. Thrombomodulin is found on endothelium of arteries, veins, capillaries and lymphatics, and on syncytiotropho-blast of human placenta.. J Cell Biol 1985; 101: 363-71.
    CrossrefPubMedGoogle Scholar
  • 6 Pruna A, Peyri N, Berard M, Boffa M-C. Thrombomodulin is synthesized by human mesangial cells.. Kidney Int 1997; 51: 687-93.
    CrossrefPubMedGoogle Scholar
  • 7 Boffa M-C. Considering cellular thrombomodulin distribution and its modulating factors can facilitate the use of plasma thrombomodulin as a reliable endothelial marker.. Haemostasis 1996; 26 (04) 233-43.
    PubMedGoogle Scholar
  • 8 Minakami H, Takahashi T, Izumi A, Tamada T. Increased levels of plasma thrombomodulin in preeclampsia.. Gynecol Obstet Invest 1993; 36: 208-10.
    CrossrefPubMedGoogle Scholar
  • 9 Hsu CD, Iriye B, Johnson TR, Witter FR, Hong SF, Chan DW. Elevated circulating thrombomodulin in severe preeclampsia.. Am J Obstet Gynecol 1993; 169: 148-9.
    CrossrefPubMedGoogle Scholar
  • 10 Bontis J, Vavilis D, Agorastos T, Zournatzi V, Konstantinidis T, Tagou K. Maternal plasma level of thrombomodulin is increased in mild preeclampsia.. Eur J Obstet Gynecol 1995; 60: 139-41.
    CrossrefPubMedGoogle Scholar
  • 11 Labarrere CA, Faulk WP. Microvascular perturbations in human allografts: analogies in preeclamptic placentae.. Am J Reproduc Immunol 1992; 27: 109-16.
    PubMedGoogle Scholar
  • 12 Davey DA, McGillvray J. The classification and definition of the hypertensive disorders of pregnancy.. Am J Obstet Gynecol 1988; 158: 592.
    PubMedGoogle Scholar
  • 13 ACOG.. Management of preeclampsia.. Washington DC: American College of Obstetricians and Gynecologists; 1986. (Technical Bulletin n 91).
    Google Scholar
  • 14 Amiral J, Adam M, Mimilla F, Larrivaz I, Chambrette B, Boffa M-C. Design and validation of a new immunoassay for soluble forms of thrombomodulin and studies on plasma.. Hybridoma 1994; 13: 205-13.
    CrossrefPubMedGoogle Scholar
  • 15 Metz CE. Basic principles of ROC analysis.. Semin Nucl Med 1978; 8: 283-98.
    CrossrefPubMedGoogle Scholar
  • 16 Goldman L. Quantitative aspects of clinical reasoning.. In: “Harrison’s Principles of Internal Medicine”.. Wilson JD, Braunwald E, Isselbacher KJ, Petersdorf RG, Martin JB, Fauci AS, Root RK. eds. New York: McGraw-Hill; 1991: 5-11.
    Google Scholar
  • 17 Boffa M-C, Aurousseau MH, Wiesel ML, Grunebaum L, Cazenave JP. Variations of thrombomodulin levels due to age and sex.. Blood 1991; S1 (78) 221 (Abst).
    PubMedGoogle Scholar
  • 18 Hsu CD, Lucas RB, Johnson TR, Hong SF, Chan DW. Elevated urine thrombomodulin/creatinine ratio in severely preeclamptic pregnancies.. Am J Obstet Gynecol 1994; 171: 854-6.
    CrossrefPubMedGoogle Scholar
  • 19 Hsu CD, Copel JA, Hong SF, Chan DW. Thrombomodulin levels in preeclampsia, gestational hypertension and chronic hypertension.. Obstet Gynecol 1995; 86: 897-9.
    CrossrefPubMedGoogle Scholar
  • 20 Beaufils M, Uzan S, Donsimoni R, Colau JC. Prevention of preeclampsia by early anti-platelet therapy.. Lancet 1985; 1: 840-4.
    PubMedGoogle Scholar
  • 21 Wallemburg HCS, Dekker GA, Makowitz JW, Rotmans P. Low-dose aspirin prevents pregnancy-induced hypertension and preeclampsia in angiotensin-sensitive primigravidae.. Lancet 1986; 1: 1-6.
    PubMedGoogle Scholar
  • 22 Italian Study of aspirin in pregnancy.. Low dose aspirin in prevention and treatment of intrauterine growth retardation and pregnancy-induced hyper-tension.. Lancet 1993; 341: 396-400.
    PubMedGoogle Scholar
  • 23 CLASP: a randomized trial of low-dose aspirin fro the prevention and treatment of preeclampsia among 9364 pregnant women.. Lancet 1994; 343: 619-29.
    CrossrefPubMedGoogle Scholar
  • 24 Collins E, Turner G. Maternal effects of regular salicylate ingestion in pregnancy.. Lancet 1975; 2: 335-8.
    PubMedGoogle Scholar
  • 25 Sibai BM, Caritis SN, Thom E, Klebanoff M, McNallis D, Rocco L, Paul RH, Romero R, Witter F, Rosen M, Depp R. The National Institute of Child Health, and the Human Development Network of Maternal-Fetal Medicine Units.. Prevention of preeclampsia with low-dose aspirin in healthy nulliparous pregnant women.. New Engl J Med 1993; 329: 1213-8.
    CrossrefPubMedGoogle Scholar
  • 26 Halligan A, Bonnar J, Sheppard B, Darling M, Walsh J. Haemostatic, fibrinolytic and endothelial variables in normal pregnancies and preeclampsia.. Br J Obstet Gynecol 1994; 101: 488-92.
    CrossrefPubMedGoogle Scholar
  • 27 Alessi MC, Boffa M-C, Menart C, Aillaud MF, Parrot G, Juhan Vague I. Venous occlusion does not induce the release of thrombomodulin from endothelial cells in patients with thromboembolic disease.. Thromb Haemost 1992; 68: 483-4.
    Article in Thieme ConnectPubMedGoogle Scholar
  • 28 Abe H, Okajima K, Okabe H, Takatsuki K, Binder BR. Granulocyte pro-teases and hydrogen peroxide synergistically inactivate thrombomodulin of endothelial cells in vitro.. J Lab Clin Med 1994; 123: 874-81.
    PubMedGoogle Scholar
  • 29 Boehme MWJ, Deng Y, Raeth U, Bierhaus A, Ziegler R, Stremmel W, Nawroth PP. Release of thrombomodulin from endothelial cells by concerted action of TNF-alpha and neutrophils: in vivo and in vitro studies.. Immunology 1996; 87: 134-40.
    PubMedGoogle Scholar
  • 30 Greer IA, Dawes J, Johnston TA, Calder AA. Neutrophil activation is confined to the maternal circulation in pregnancy-induced hypertension.. Obstet Gynecol 1991; 78: 28-32.
    PubMedGoogle Scholar
  • 31 Tsukimori K, Maeda H, Ishida K, Nagata H, Koyanagi T, Nakano H. The superoxide generation of neutrophils in normal and preeclamptic pregnancies.. Obstet Gynecol 1993; 81: 536-40.
    PubMedGoogle Scholar
  • 32 Asakura H, Jokaji H, Saito M, Uotani C, Kumabashiri I, Morishita E, Yamazaki M, Matsuda T. Plasma levels of soluble thrombomodulin increase in cases of disseminated intravascular coagulation with organ failure.. Am J Hematol 1991; 38: 281-7.
    CrossrefPubMedGoogle Scholar