Pro- and Anticoagulatory Factors under Sodium Valproate-Therapy in Children

Abstract

Objective

To evaluate sodium valproate-induced hemostatic side effects in children.

Methods

A variety of both pro- and anticoagulatory parameters were longitudinally investigated in 80 children before therapy and up to 720 days after initiation of sodium valproate (VPA) therapy.

Results

VPA caused a significant reduction in platelet count (309 000/µl ± 122 000 before treatment to 261 000/µl ± 150 000 under VPA therapy, p = 0.007). However platelet function was not impaired. While vWF antigen was reduced during VPA therapy (1.05 U/ml ± 0.4 U/ml before therapy, 0.95 ± 0.4 U/ml under VPA therapy), the in vivo activity of vWF (ratio between function and antigen concentration) increased significantly (1.06 ± 0.2 before therapy, 1.36 ± 0.3 under VPA therapy, p = 0.01). Both procoagulatory and anticoagulatory factors were significantly reduced (fibrinogen: 264.5 ± 64.5 mg/dl before therapy, 221.4 ± 47.5 mg/dl under therapy, p = 0.001; protein C: 81.3 % ± 18 before therapy, 65.6 % ± 21.4 under VPA therapy, p = 0.005, antithrombin: 122.7 % ± 23.7 before therapy, 101.7 % ± 18 under VPA therapy, p = 0.04). With the exception of fibrinogen, these effects were identical in children treated either with monotherapy or with polytherapy.

Conclusions

Besides already known alterations of a variety of procoagulatory parameters, a relevant influence of VPA on the anticoagulatory system is demonstrated. We hypothesize that this additional alteration of anticoagulatory parameters might reduce the absolute bleeding risk of children treated with VPA.

Key words

Antithrombin - Platelets - Protein C - von Willebrand Factor

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