Download PDF
Neuropediatrics 2007; 38(1): 42-45
DOI: 10.1055/s-2007-981448
Short Communication

© Georg Thieme Verlag KG Stuttgart · New York

Severe Bleeding Complications during Antiepileptic Treatment with Valproic Acid in Children[*]

E. Cannizzaro 1 , M. Albisetti 1 , G. Wohlrab 1 , M. Schmugge 1
  • 1Division of Haematology and Neurology, University Children's Hospital, Zurich, Switzerland
Further Information

Publication History

received 9. 11. 2006

accepted 27. 3. 2007

Publication Date:
02 July 2007 (online)

    Permissions and Reprints

Abstract

Valproic acid (VPA) is an antiepileptic drug frequently used in children. Although VPA can cause a variety of laboratory abnormalities affecting haemostasis, controversy exists about the clinical relevance of such haematological abnormalities. We report on 4 children with severe bleeding complications while on VPA therapy; two presented with intracranial bleeding, while two suffered from severe bleeding postoperatively. Diagnostic and therapeutic measures are discussed that help to avoid severe bleeding complications in children with VPA treatment.

Key words

Epilepsy - valproic acid - von Willebrand factor - platelets - coagulation

1 Presented in part at the 47nd annual meeting of the American Society of Haematology, Atlanta, Georgia, December 2005.

References

  • 1 Anderson GD, Temkin NR, Chandler WL, Winn HR. Effect of valproate on haemostatic function in patients with traumatic brain injury.  Epilepsy research. 2003;  57 111-119
    CrossrefPubMedGoogle Scholar
  • 2 Argyriou AA, Tsota I, Solomou E, Marangos M, Kalogeropoulou C, Petsas T. et al . Intracerebral haemorrhage as a rare complication of HSV-1 meningoencephalitis: Case report and review of the literature.  Scand J Infect Dis. 2006;  38 63-66
    PubMedGoogle Scholar
  • 3 Banerjea MC, Diener W, Kutschke G, Schneble HJ, Korinthenberg R, Sutor AH. Pro- and anticoagulatory factors under sodium valproate therapy in children.  Neuropaediatrics. 2002;  33 215-220
    Article in Thieme ConnectPubMedGoogle Scholar
  • 4 Chambers HG, Weinstein CH, Mubarak SJ, Wenger DR, Silva PD. The effect of valproic acid on blood loss in patients with cerebral palsy.  J Paediatr Orthop. 1999;  19 792-795
    PubMedGoogle Scholar
  • 5 Gerstner T, Teich M, Bell N, Longin E, Dempfle C, Brand J. et al . Valproate-associated coagulopathies are frequent and variable in children.  Epilepsia. 2006;  47 1136-1143
    CrossrefPubMedGoogle Scholar
  • 6 Gidal B, Spencer N, Maly M, Pitterle M, Williams E, Collins M. et al . Valproate-mediated disturbances of haemostasis.  Neurology. 1994;  44 1418-1422
    PubMedGoogle Scholar
  • 7 Harrison P. The role of PFA-100 testing in the investigation and management of haemostatic defects in children and adults.  B J Haematol. 2005;  130 3-10
    CrossrefPubMedGoogle Scholar
  • 8 Konig S, Scheffner D, Rauterberg-Ruland I, Kochen W, Hofmann WJ, Wokittel E. et al . Fatal hepatic failure in a normally developed 5-year-old boy by VPA monotherapy.  Monatsschr Kinderheilkd. 1987;  135 310-313
    PubMedGoogle Scholar
  • 9 Kreuz W, Linde R, Funk M, Meyer-Schrod R, Föll E, Nowak-Göttl U. et al . Valproate therapy induces von Willebrand disease type I.  Epilepsia. 1992;  33 178-184
    PubMedGoogle Scholar
  • 10 Kuendgen A, Strupp C, Aivado M, Bernhardt A, Hildebrandt B, Haas R. et al . Treatment of myelodysplastic syndromes with valproic acid alone or in combination with all-trans-retinoic acid.  Blood. 2004;  104 1266-1269
    CrossrefPubMedGoogle Scholar
  • 11 Larkin D, Murphy D, Reilly DF, Cahill M, Sattler E, Harriott P. et al . ICln, a novel integrin αIIbβ3-associated protein, functionally regulates platelet activation.  J Biol Chem. 2004;  279 27286-27293
    CrossrefPubMedGoogle Scholar
  • 12 Perucca E. Pharmacological and therapeutic properties of valproate: a summary after 35 years of clinical experience.  CNS Drugs. 2002;  16 695-714
    CrossrefPubMedGoogle Scholar
  • 13 Peterson GM, Naunton M. Valproate: a simple chemical with so much to offer.  J Clinical Pharmacy and Therapeutics. 2005;  30 417-421
    PubMedGoogle Scholar
  • 14 Pohlmann-Eden B, Peters CAN, Wennberg R, Dempfle CE. Valproate induces reversible factor XIII deficiency with risk of perioperative bleeding.  Acta Neurol Scand. 2003;  108 142-145
    CrossrefPubMedGoogle Scholar
  • 15 Rosenberg HK, Ortega W. Haemorrhagic pancraetitis in a young child following valproic acid therapy. Clinical and ultrasonic assessment.  Clin Paediatr (Phila). 1987;  26 98-101
    PubMedGoogle Scholar
  • 16 Sleiman C, Raffy O, Roué C, Mal H. Fatal pulmonary haemorrhage during high-dose valproate monotherapy [letter].  Chest. 2000;  117 613
    CrossrefPubMedGoogle Scholar
  • 17 Verrotti A, Greco R, Matera V, Altobelli E, Morgese G, Chiarelli F. Platelet count and function in children receiving sodium valproate.  Paediatr Neurol. 1999;  21 611-614
    CrossrefPubMedGoogle Scholar
  • 18 Zeller JA, Schlesinger S, Runge U, Kessler C. Influence of valproate monotherapy on platelet activation and hematologic values.  Epilepsia. 1999;  40 186-189
    CrossrefPubMedGoogle Scholar

1 Presented in part at the 47nd annual meeting of the American Society of Haematology, Atlanta, Georgia, December 2005.

Correspondence

M. Schmugge

Division of Haematology

University Children's Hospital Zürich

Steinwiesstrasse 75

8032 Zürich

Switzerland

Phone: +41/44/266 71 11

Fax: +41/44/266 71 71

Email: markus.schmugge@kispi.unizh.ch

      >