Skip to main content
SpringerLink
Log in

Coumarin embryopathy in an extremely low birth weight infant associated with neonatal hepatitis and ocular malformations

  • Original Paper
  • Published:
European Journal of Pediatrics Aims and scope Submit manuscript

Abstract

Coumarin embryopathy (CE) is a well-documented sequelae of prenatal exposure to vitamin K antagonists. We report on a female premature infant (25 weeks' gestation) born to a mother who had received phenprocoumon during pregnancy following mechanical heart valve replacement. The infant presented with impaired coagulation, intraventricular and minor parenchymal cerebral haemorrhages and midface hypoplasia typical of CE. In addition, there was hepatopathy with conjugated hyperbilirubinemia, elevated liver enzymes and repeated episodes of hypoglycemia upon attempts to discontinue glucose supplementation, all lasting for 4 months. There was corneal opacity with anterior segment dygenesis in the left eye, and persistent pupillary membrane, cataract and persistent hyperplastic primary vitreous in the right eye. While liver disease is an uncommon but serious side effect of vitamin K antagonists, this is the first report describing neonatal hepatopathy as part of CE. In anticoagulation of pregnant women with mechanical heart valves, vitamin K antagonists should be used with utmost restraint.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

Abbreviations

CE:

Coumarin embryopathy

INR:

International normalised ratio

References

  1. ACOG committee opinion (1999) Anticoagulation with low molecular weight heparin during pregnancy. Int J Gyn Obstet 65:89–90

    Article  Google Scholar 

  2. Bates SM, Greer IA, Hirsh J, Ginsberg JS (2004) Use of antithrombotic agents during pregnancy: the seventh ACCP conference on antithrombotic and thrombolytic therapy. Evidence based guidelines. Chest 126:627S–644S

    Article  PubMed  CAS  Google Scholar 

  3. Cauli C, Fenu L, Perra A, Marongiu F (2004) Amoxicillin-clavulanic acid and oral anticoagulants: a possible dangerous association. Ann Ital Med Int 19:276–279

    PubMed  Google Scholar 

  4. Chan WS, Anand S, Ginsberg JS (2000) Anticoagulation of pregnant women with mechanical heart valves a systematic review of the literature. Arch Intern Med 160:191–196

    Article  PubMed  CAS  Google Scholar 

  5. de Man RA (1993) Phenprocoumon-induced liver failure. Neth J Med 43:91

    PubMed  Google Scholar 

  6. de Man RA, Wilson JPH, Schalm SW, ten Kate FJW, Van Leer E (1990) Phenprocoumon-induced hepatits mimicking non-A, non-B hepatitis. J Hepatol 11:318–321

    Article  PubMed  Google Scholar 

  7. DiSaia PJ (1966) Pregnancy and delivery of a patient with a Starr-Edwards mitral valve prosthesis. Obstet Gynecol 28:469–472

    Google Scholar 

  8. Ginsberg JS (1999) Thromboembolism and pregnancy. Throm Haemost 82:620–625

    CAS  Google Scholar 

  9. Ginsberg JS, Kowalchuk G, Hirsh J (1989) Risk to the fetus of anticoagulant therapy during pregnancy. Arch Intern Med 149:2233–2236

    Article  PubMed  CAS  Google Scholar 

  10. Gresser U (2001) Amoxicillin-clavulanic acid therapy may be associated with severe side effects – review of the literature. Eur J Med Res 6:139–149

    PubMed  CAS  Google Scholar 

  11. Hautekeete M, Holvoet J, Hubens H (1995) Cytolytic hepatitis related to the oral anticoagulant phenprocoumon. Gastroenterol Clin Biol 19:223–224

    PubMed  CAS  Google Scholar 

  12. Höhler T, Schnütgen M, Helmreich-Becker I, Mayet WJ, Mayer zum Bueschenfelde KH (1994) Drug-induced hepatitis: a rare complication of oral anticoagulants. J Hepatol 21:447–449

    Article  PubMed  Google Scholar 

  13. Kaplan LC (1985) Congenital Dandy Walker malformation associated with first trimester warfarin: a case report and literature review. Teratology 32:333–337

    Article  PubMed  CAS  Google Scholar 

  14. Lee WM (1995) Drug-induced hepatotoxicity. N Engl J Med 333:1118–1127

    Article  PubMed  CAS  Google Scholar 

  15. Montalescot G, Polle V, Collet JP (2000) Low-molecular-weight heparin after mechanical heart valve replacement. Circulation 101:1083–8106

    PubMed  CAS  Google Scholar 

  16. Mix H, Wagner S, Böker K, Gloger S, Oldhafer KJ, Behrend M, Flemming P, Mann MP (1999) Subacute liver failure induced by phenprocoumon treatment. Digestion 60:579–582

    Article  PubMed  CAS  Google Scholar 

  17. Sanson BJ, Lensing AWA, Prins MH (1999) The use of low-molecular-weight heparin in pregnancy. Thromb Haemost 81:668–672

    PubMed  CAS  Google Scholar 

  18. Schimanski CC, Burg J, Möhler K, Höhler T, Kanzler S, Otto G, Galle PR, Lohse AW (2004) Phenprocoumon-induced liver diseases range from mild acute hepatitis to (sub-) acute liver failure. J Hepatol 41:67–74

    Article  PubMed  CAS  Google Scholar 

  19. Slagboom G, Loeliger EA (1980) Coumarin-associated hepatitis. Arch Intern Med 140:1028–1029

    Article  PubMed  CAS  Google Scholar 

  20. Task Force on the Management of Cardiovascular Diseases During Pregnancy of the European Society of Cardiology (2003) Expert consensus document on management of cardiovascular diseases during pregnancy. Eur Heart J 24:761–781

    Article  Google Scholar 

  21. Van Driel D, Wesseling J, Sauer PJJ, Touwen BCL, Van Der Veer E, Heymans HSA (2002) Teratogen update: fetal effects after, in utero exposure to coumarins, overview of cases, follow-up findings, and pathogenesis. Teratology 66:127–140

    Article  PubMed  Google Scholar 

  22. Vitale N, De Feo M, De Santo LS, Pollice A, Tedesco N, Cotrufo M (1999) Dose-dependent fetal complications of warfarin in pregnant women with mechanical heart valves. J Am Coll Cardiol 33:1637–1641

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Neonatology, University Children’s Hospital, Basel, Switzerland

    Patrick G. Hetzel, René Glanzmann & Christoph Bührer

  2. Department of Ophthalmology, University Hospital, Basel, Switzerland

    Pascal W. Hasler

  3. University Women’s Hospital, Basel, Switzerland

    Ariane Ladewick

  4. Universitäts-Kinderspital beider Basel, CH-4005, Basel, Switzerland

    Patrick G. Hetzel

Authors
  1. Patrick G. Hetzel
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. René Glanzmann
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Pascal W. Hasler
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Ariane Ladewick
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Christoph Bührer
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Patrick G. Hetzel.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Hetzel, P.G., Glanzmann, R., Hasler, P.W. et al. Coumarin embryopathy in an extremely low birth weight infant associated with neonatal hepatitis and ocular malformations. Eur J Pediatr 165, 358–360 (2006). https://doi.org/10.1007/s00431-005-0064-1

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00431-005-0064-1

Keywords

Search

Navigation