title: Effects of chronic administration of valproic acid to epileptic patients on coagulation tests and primary hemostasis.
abstract: Valproic acid (VPA) is an antiepileptic drug that has been associated with impaired hemostasis and increased risk for postsurgical bleeding. However, the published reports provide controversial results. We measured parameters of primary hemostasis in VPA-treated patients with epilepsy, focusing on adenosine nucleotide-dependent platelet responses, which play a central role in primary hemostasis. We enrolled 20 cases (epileptic patients receiving treatment with VPA) and 20 controls (12 epileptic patients receiving treatment with drugs different from VPA and 8 healthy subjects). Measurements included prothrombin time (PT), activated partial thromboplastin time (APTT), platelet count, platelet function analyzer (PFA)-100 closure times, plasma von Willebrand factor levels, platelet content of ADP, ATP, and serotonin (all stored in platelet dense granules), and platelet shape change and aggregation induced by ADP and other platelet agonists, including the ATP analog α,β-methylene-ATP. The plasma concentration of VPA was in the therapeutic range in 17 patients and slightly above the upper limit in 3 patients. There were no statistically significant differences in any of the studied parameters in cases versus controls. Our thorough controlled study failed to show that chronic treatment with VPA induces significant abnormalities of coagulation and primary hemostasis. Therefore, VPA, when present in the circulation in the therapeutic range, does not impair hemostasis.
authors.affiliation: Medicine Unit 3, San Paolo Hospital, Milan, Italy.
authors.forename: Maddalena L
authors.initials: ML
authors.lastname: Zighetti
authors.affiliation: Medicine Unit 3, San Paolo Hospital, Milan, Italy.
authors.forename: Gessica
authors.initials: G
authors.lastname: Fontana
authors.affiliation: Medicine Unit 3, San Paolo Hospital, Milan, Italy.
authors.forename: Federico
authors.initials: F
authors.lastname: Lussana
authors.affiliation: Neurology Unit 2, Epilepsy Center, San Paolo Hospital, Milan, Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: Chiesa
authors.affiliation: Neurology Unit 2, Epilepsy Center, San Paolo Hospital, Milan, Italy.|Department of Health Sciences, University of Milan, Milan, Italy.
authors.forename: Aglaia
authors.initials: A
authors.lastname: Vignoli
authors.affiliation: Neurology Unit 2, Epilepsy Center, San Paolo Hospital, Milan, Italy.|Department of Health Sciences, University of Milan, Milan, Italy.
authors.forename: Maria Paola
authors.initials: MP
authors.lastname: Canevini
authors.affiliation: Medicine Unit 3, San Paolo Hospital, Milan, Italy.|Department of Health Sciences, University of Milan, Milan, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Cattaneo
mesh_terms: D000244:Adenosine Diphosphate / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000293:Adolescent; D000328:Adult; D000927:Anticonvulsants / Q000009:adverse effects*; D001778:Blood Coagulation Disorders / Q000139:chemically induced*; D016022:Case-Control Studies; D002648:Child; D004334:Drug Administration Schedule; D004827:Epilepsy / Q000188:drug therapy*; D005260:Female; D006487:Hemostasis / Q000187:drug effects*; D006801:Humans; D008297:Male; D010979:Platelet Function Tests; D011516:Prothrombin / Q000378:metabolism; D012701:Serotonin / Q000097:blood; D013925:Thromboplastin / Q000378:metabolism; D013997:Time Factors; D014635:Valproic Acid / Q000009:adverse effects*; D055815:Young Adult
chemical_list: D000927:Anticonvulsants; D012701:Serotonin; D014635:Valproic Acid; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D011516:Prothrombin; D013925:Thromboplastin
keywords: Antiepileptic drugs; Case-control studies; Platelet function; Thrombocytopenia; von Willebrand factor