Valproate-associated coagulopathies in children during short-term treatment

J Child Neurol. 2009 Dec;24(12):1493-8. doi: 10.1177/0883073808331084. Epub 2009 May 28.

Abstract

Valproic acid is one of the most frequently prescribed antiepileptic drugs for the therapy of generalized and focal epilepsies. Valproate induces a variety of hemostatic disorders such as thrombocytopenia, abnormal platelet function, hypofibrinogenemia, and decreased concentrations of von Willebrand factor, and it rarely causes serious bleeding complications. It may also lead to atherosclerosis and thrombosis. However, there is still lack of knowledge about the incidence and occurrence of these particular side effects. In this prospective systematic study, we assessed the early effects of sodium valproate on both pro- and anticoagulatory factors, homocysteine, and lipoprotein (a) in 24 newly diagnosed epileptic children treated with valproate. Valproate causes decreased factor VII levels, platelet count, factor VIII, Protein C, fibrinogen, and increased lipoprotein (a) levels. To the best of our knowledge, our report is the first in the medical literature, which describes that valproate significantly reduces factor VII levels even during short-term therapy.

MeSH terms

  • Adolescent
  • Anticonvulsants / administration & dosage
  • Anticonvulsants / adverse effects*
  • Biomarkers / analysis
  • Biomarkers / blood
  • Blood Coagulation Disorders / chemically induced*
  • Blood Coagulation Disorders / metabolism
  • Blood Coagulation Disorders / physiopathology
  • Blood Coagulation Factors / drug effects*
  • Blood Coagulation Factors / metabolism
  • Blood Protein Disorders / chemically induced*
  • Blood Protein Disorders / metabolism
  • Blood Protein Disorders / physiopathology
  • Child
  • Child, Preschool
  • Down-Regulation / drug effects
  • Down-Regulation / physiology
  • Drug Administration Schedule
  • Epilepsy / drug therapy
  • Factor VII / drug effects
  • Factor VII / metabolism
  • Factor VIII / drug effects
  • Factor VIII / metabolism
  • Female
  • Fibrinogen / drug effects
  • Fibrinogen / metabolism
  • Homocysteine / drug effects
  • Homocysteine / metabolism
  • Humans
  • Lipoprotein(a) / drug effects
  • Lipoprotein(a) / metabolism
  • Male
  • Platelet Count
  • Prospective Studies
  • Protein C / drug effects
  • Protein C / metabolism
  • Valproic Acid / administration & dosage
  • Valproic Acid / adverse effects*

Substances

  • Anticonvulsants
  • Biomarkers
  • Blood Coagulation Factors
  • Lipoprotein(a)
  • Protein C
  • Homocysteine
  • Valproic Acid
  • Factor VII
  • Factor VIII
  • Fibrinogen