Riten Kumar1, Jorge Vidaurre2, Satyanarayana Gedela3. 1. Division of Pediatric Hematology/Oncology, Nationwide Children's Hospital, Columbus, Ohio; Department of Pediatrics, The Ohio State University, Columbus, Ohio. 2. Department of Pediatrics, The Ohio State University, Columbus, Ohio; Division of Pediatric Neurology, Nationwide Children's Hospital, Columbus, Ohio. 3. Department of Pediatrics, The Ohio State University, Columbus, Ohio; Division of Pediatric Neurology, Nationwide Children's Hospital, Columbus, Ohio. Electronic address: satyanarayana.gedela@emory.edu.
Abstract
BACKGROUND: Valproic acid is one of the most commonly used antiseizure medications. Multiple hematologic abnormalities have been reported with the use of valproic acid, which may be particularly relevant in the perioperative surgical setting. The incidence of these abnormalities and prevalence of periprocedural hemorrhage vary significantly in the published literature. In this article we analyze the prevalence and possible etiology of coagulopathy and hemorrhage in patients receiving valproic acid. METHODS: A literature search was completed using "VPA," "coagulopathy," and "surgery." The available published data from case reports to large case series were reviewed. RESULTS: Thrombocytopenia was noted to be the most common laboratory abnormality associated with valproic acid. An association between valproic acid and acquired von Willebrand disease has also been suggested. There are case reports describing bleeding in the setting of hypofibrinogenemia and factor XIII deficiency. Perioperative hemorrhage was reported in pediatric studies of orthopedic procedures, but not in adult cohorts undergoing neurosurgical interventions. CONCLUSIONS: VPA use can cause thrombocytopenia and other coagulation abnormalities. Rigorous, prospective trials are needed to better assess the association between valproic acid and clinically significant coagulopathy. Until such data are available, physicians need to be aware of the potential risk of bleeding in patients receiving valproic acid. A hemostatic evaluation should be considered in symptomatic patients, and may be considered for patients taking VPA who are scheduled for surgery. If an abnormality is detected, hematologists should be involved to make recommendation on perioperative hemostatic strategy.
BACKGROUND:Valproic acid is one of the most commonly used antiseizure medications. Multiple hematologic abnormalities have been reported with the use of valproic acid, which may be particularly relevant in the perioperative surgical setting. The incidence of these abnormalities and prevalence of periprocedural hemorrhage vary significantly in the published literature. In this article we analyze the prevalence and possible etiology of coagulopathy and hemorrhage in patients receiving valproic acid. METHODS: A literature search was completed using "VPA," "coagulopathy," and "surgery." The available published data from case reports to large case series were reviewed. RESULTS:Thrombocytopenia was noted to be the most common laboratory abnormality associated with valproic acid. An association between valproic acid and acquired von Willebrand disease has also been suggested. There are case reports describing bleeding in the setting of hypofibrinogenemia and factor XIII deficiency. Perioperative hemorrhage was reported in pediatric studies of orthopedic procedures, but not in adult cohorts undergoing neurosurgical interventions. CONCLUSIONS: VPA use can cause thrombocytopenia and other coagulation abnormalities. Rigorous, prospective trials are needed to better assess the association between valproic acid and clinically significant coagulopathy. Until such data are available, physicians need to be aware of the potential risk of bleeding in patients receiving valproic acid. A hemostatic evaluation should be considered in symptomatic patients, and may be considered for patients taking VPA who are scheduled for surgery. If an abnormality is detected, hematologists should be involved to make recommendation on perioperative hemostatic strategy.