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Thrombophilic risk factors in epileptic children treated with valproic Acid
Ozlem Unal1, Gülhis Deda, Serap Teber
1Department of Pediatric Neurology, Medicine Faculty, Ankara University, Ankara, Turkey. unalozlem@gmail.com
Insights
Valproic acid treatment in children with epilepsy may alter thrombophilia risk factors, notably increasing lipoprotein(a) and decreasing fibrinogen. Routine screening is not advised unless a child has a history of stroke or thrombotic events.
Area of Science:
- Pediatric Neurology
- Hematology
- Pharmacology
Background:
- Valproic acid is a common antiepileptic drug.
- Limited data exists on valproic acid's association with thrombophilia.
- Thrombophilia involves an increased tendency to form blood clots.
Purpose of the Study:
- To investigate thrombophilic risk factors in children with epilepsy treated with valproic acid.
- To assess changes in specific thrombophilic markers before and after valproic acid therapy.
Main Methods:
- Evaluated 21 children (ages 1-13) with epilepsy on new valproic acid monotherapy.
- Measured homocysteine, lipoprotein(a), factor VIII, factor IX, protein C, protein S, antithrombin III, and activated protein C resistance.
- Assessed thrombosis gene mutations (factor V Leiden, prothrombin G20210A) before treatment.
Main Results:
- Statistically significant increase in lipoprotein(a) levels post-treatment.
- Statistically significant decrease in fibrinogen levels post-treatment.
- Observed, but not statistically significant, reductions in protein C and increases in homocysteine.
Conclusions:
- Valproic acid may increase thrombotic risk by elevating lipoprotein(a) and decreasing fibrinogen.
- No clinical adverse effects were noted despite laboratory changes.
- Routine thrombophilia screening before valproic acid initiation is not generally recommended, but caution is advised for children with prior thrombotic events.
Abstract:
There are few reports on valproic acid related to thrombophilia. Thrombophilic risk factors were investigated in 21 children (age range, 1-13 years) diagnosed with epilepsy and newly treated with valproic acid monotherapy. None of the children had been previously treated with any anticonvulsant agent. Before starting valproic acid therapy, homocysteine, lipoprotein(a), factor VIII, factor IX, protein C, protein S, antithrombin III levels, and activated protein C resistance levels were evaluated in all patients, with repeat evaluation after 9 months or 1 year of the therapy. Thrombosis gene mutations (factor V Leiden and prothrombin G20210A) were also evaluated in all patients before therapy. There was statistically significant elevation in lipoprotein(a) levels and reduction in fibrinogen levels after treatment. Reduction in protein C levels and elevation in homocysteine levels were also observed, but without statistical significance. Before therapy, no thrombotic event had occurred, despite thrombotic risk factors in some patients. Valproic acid can increase lipoprotein(a) and decrease fibrinogen, which may increase the risk of stroke or other thrombotic events. No clinical adverse effects resulted from changes in the levels or activity of thrombophilic factors associated with valproic acid treatment. Thus, routine investigation of factors implicated in thrombosis prior to initiation of valproic acid is not warranted for all patients. Nonetheless, caution is advised when initiating valproic acid treatment in children who have had prior stroke or thrombotic events.
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