Factor VII deficiency associated with valproate treatment

It has long been known that the anti-epileptic, valproate (VPA), which is used widely in the treatments of generalized and focal seizures, may cause subclinical alterations in both intrinsic and extrinsic coagulation pathways. These changes include thrombocyte dysfunction, thrombocytopenia, von Willebrand disease type I, deficiency of vitamin K-dependent coagulation factors 11, VII, IX, and X and reduction in serum fibrinogen, protein C and protein S concentrations. In addition macrocytosis, erythrocytopenia, neutropenia, reduction in hemoglobin and hematocrit counts and bone marrow suppression are reported to accompany VPA treatment. The incidence of these disturbances is higher in children than in adults.(1) These side-effects of VPA may either be dose related, or idiosyncratic, but life-threatening hemorrhage in such cases is rare. The aforementioned hernatological disturbances are generally identified following chronic VPA treatment and when VPA blood concentrations are >100 mu/mL;(2) they can be recurring, temporary or permanent