title: The effect of valproate therapy on thrombin generation determined by calibrated automated thrombography.
abstract: BACKGROUND
  There is some evidence for coagulation disorders, e.g. decreased coagulation factor activity or thrombocytopenia, related to the use of antiepileptic drugs, mainly associated with valproate. The aim of our study was to evaluate the influence of valproate on thrombin generation.
  
  
  METHODS
  Patients with epilepsy receiving multiple anticonvulsant medications either with, or without, valproate were compared. The study group included 90 samples from patients with epilepsy, aged 1.3-20.1 years. Antiepileptic combination therapy without valproate was administered in 50 cases and therapy including valproate in 40 cases. The reference group consisted of 50 non-epileptic patients. Thrombin generation in platelet poor plasma was measured by calibrated automated thrombography.
  
  
  RESULTS
  No differences were measured for thrombin generation parameters between controls and patients without valproate therapy. In epileptic patients with valproate therapy, peak height and lag time were significantly lower in comparison to non-epileptic patients. In comparison to epileptic patients without valproate therapy, significant differences were found for lag time and peak time. Patients with valproate therapy had a significantly lower fibrinogen concentration. Platelet counts were decreased in a dose dependent manner.
  
  
  CONCLUSIONS
  No major differences in thrombin generation were found between children on antiepileptic therapy with and without valproate. The decreased fibrinogen levels result in shorter lag time and peak time.
authors.affiliation: Pediatrics, University of Erlangen, Germany.
authors.forename: H-G
authors.initials: HG
authors.lastname: Topf
authors.forename: G
authors.initials: G
authors.lastname: Lischetzki
authors.forename: R
authors.initials: R
authors.lastname: Trollmann
authors.forename: W
authors.initials: W
authors.lastname: Rascher
authors.forename: M
authors.initials: M
authors.lastname: Rauh
mesh_terms: D000293:Adolescent; D000927:Anticonvulsants / Q000009:adverse effects* / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D004359:Drug Therapy, Combination; D004827:Epilepsy / Q000097:blood* / Q000188:drug therapy*; D005260:Female; D005340:Fibrinogen / Q000378:metabolism; D006801:Humans; D007223:Infant; D008297:Male; D010314:Partial Thromboplastin Time; D010976:Platelet Count; D012016:Reference Values; D013916:Thrombelastography / Q000187:drug effects*; D013917:Thrombin / Q000378:metabolism*; D014635:Valproic Acid / Q000009:adverse effects* / Q000627:therapeutic use; D055815:Young Adult
chemical_list: D000927:Anticonvulsants; D014635:Valproic Acid; D005340:Fibrinogen; D013917:Thrombin