Summary:Purpose: Valproic acid (VPA) is an antiepileptic drug (AED) commonly used for generalized and focal epilepsies. The clinical relevance of coagulopathies, known as side effects of VPA therapy, especially thrombocytopenia, von Willebrand disease, and a decrease of factor XIII, is still unclear.Methods: In our institute, we noticed a high incidence of clinically relevant coagulation problems related to VPA in eight patients within 1 year only and a further seven children with significant coagulopathy were identified in the context of planned surgery. Results:We provide an overview of these patients and all six VPA-induced coagulopathies.Conclusions: At this time, it cannot be recommended to control all hemostatic parameters in every patient. Whenever an increased bleeding tendency is observed, or before surgical procedures, a platelet count, thrombelastography, prothrombin time, activated partial thromboplastin time, TT, fibrinogen, von Willibrand factor, and factor XIII should be examined. With 385 VPAtreated patients per year and 15 cases of coagulation disorders in this period, we estimate the incidence of coagulation disorders related to VPA in children to be nearly 4%.

The difference between 90 patients reported worldwide from 1979 to 2005 and the 16 new documented cases from only Germany over 10 years corroborates that the occurrence of this severe side effect is under reported.

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Acute hemorrhagic edema of infancy (AHEI) is a cutaneous leukocytoclastic vasculitis that usually occurs in children younger than 2 years of age. It is a rare disease characterized by mild fever, a violent onset of hemorrhagic skin lesions, and edema usually followed by a spontaneous and complete recovery. Although the etiology is unknown, AHEI often follows infections, drug treatment, or vaccination. In the present report, the authors describe 4 cases of AHEI and review the relevant literature.