| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
University of Wisconsin School of Pharmacy (Dr. Gidal, and M. Pitterle and M. Collins), and the Departments of Neurology (Drs. Gidal, Spencer, and Jones, and M. Maly) and Medicine (Dr. Williams), Madison, WI.
Valproic acid (VPA) may cause impaired platelet function, thrombocytopenia and, occasionally, severe bleeding. Controversy exists both as to the mechanism of this alteration in hemostasis and as to whether these adverse effects are either dose-related or idiosyncratic. Previous investigations have focused primarily on pediatric patients who commonly were receiving multiple anticonvulsant medications. We evaluated a cohort of 27 adult patients with epilepsy who were receiving VPA monotherapy and compared them with age-matched controls to determine whether a correlation exists between platelet count, function, bleeding time, levels of von Willebrand's factor antigen, and VPA dose or plasma concentration. VPA patients had significantly lower platelet counts and longer bleeding times than did controls (p < 0.05). Platelet count was inversely correlated to VPA dose and both free and total VPA concentration (p < 0.01). There was no significant difference in levels of von Willebrand's factor antigen between patients and controls. We assessed platelet aggregation by measurement of whole-blood platelet aggregation and release with agonists including adenosine diphosphate, thrombin, collagen, arachidonic acid, and ristocetin. VPA patients had significant decreases in platelet aggregation values compared with controls. There were significant differences in collagen, arachidonic acid, and adenosine diphosphate release and aggregation between groups that correlated to both VPA dose (p < 0.01) and concentration (p < 0.05). Prolongation of bleeding time was significantly correlated to both VPA dose and concentration. Our data suggest a significant relationship between impaired platelet function and both VPA dose and plasma concentration.
Address correspondence and reprint requests to Dr. Barry E. Gidal, University of Wisconsin, School of Pharmacy, 425 N. Charter Street, Madison, WI 53706.
Supported in part by Abbott Laboratories, North Chicago, IL.
Received November 29, 1993. Accepted in final form February 7, 1994.
This article has been cited by other articles:
|
|
 |
|
  J. A. French and T. A. Pedley Initial Management of Epilepsy N. Engl. J. Med., July 10, 2008; 359(2): 166 - 176. [Full Text] [PDF]
|
|
|
|
 |
|
 J. P. Veinot and M. Ruel Valproic Acid and Bleeding: Caution Required Ann. Thorac. Surg., February 1, 2007; 83(2): 725 - 725. [Full Text] [PDF]
|
|
|
|
 |
|
 R. M.A. Hirschfeld, C. L. Bowden, M. J. Gitlin, P. E. Keck, R. H. Perlis, T. Suppes, M. E. Thase, and K. D. Wagner Practice Guideline for the Treatment of Patients With Bipolar Disorder (Revision) Focus, January 1, 2003; 1(1): 64 - 110. [Full Text] [PDF]
|
|
|
|
 |
|
 R. J. Baumann Technical Report: Treatment of the Child With Simple Febrile Seizures Pediatrics, June 1, 1999; 103(6): 86e - 86. [Abstract] [Full Text]
|
|
|
|
 |
|
 R. Selby, E. Nisbet-Brown, R. K. Basran, L. Chang, and N. F. Olivieri Valproic Acid and Augmentation of Fetal Hemoglobin in Individuals With and Without Sickle Cell Disease Blood, July 15, 1997; 90(2): 891 - 892. [Full Text] [PDF]
|
|
|
|
 |
|
 D. A. Tam Jr and E. C. Myer Vitamin K-Dependent Coagulopathy in a Child Receiving Anticonvulsant Therapy J Child Neurol, May 1, 1996; 11(3): 244 - 246. [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
