Assessment of need for hemostatic evaluation in patients taking valproic acid: A retrospective cross-sectional study

Abstract

Introduction: Valproic acid (VPA) is a frequently prescribed anti-epileptic drug. Since its introduction side effects on hemostasis are reported. However, studies show conflicting results, and the clinical relevance is questioned. We aimed to determine the coagulopathies induced by VPA in patients who undergo high-risk surgery. The study results warrant attention to this issue, which might contribute to reducing bleeding complications in future patients.

Methods: Between January 2012 and August 2020, 73 consecutive patients using VPA were retrospectively included. Extensive laboratory hemostatic assessment (including platelet function tests) was performed before elective high-risk surgery. Patient characteristics, details of VPA treatment, and laboratory results were extracted from medical records.

Results: 46.6% of the patients using VPA (n = 73) showed coagulopathy. Mainly, platelet function disorder was found (36.4%). Thrombocytopenia was seen in 9.6% of the patients. Data suggested that the incidence of coagulopathies was almost twice as high in children as compared to adults and hypofibrinogenemia was only demonstrated in children. No association was found between the incidence of coagulopathies and VPA dosage (mg/kg/day).

Conclusion: A considerable number of patients using VPA were diagnosed with coagulopathy, especially platelet function disorder. Further prospective studies are needed to confirm the need for comprehensive laboratory testing before elective high-risk surgery in these patients.

Fig 1. Number of patients with the different combinations of abnormalities in LTA (maximal aggregation) using valproic acid.

Abbreviations: AA = arachidonic acid 1 mmol/L; ADP-5 = adenosine diphosphate 5 μmol/L; ADP-10 = adenosine diphosphate 10 μmol/L; COL-1 = collagen 1 μg/mL; COL-4 = collagen 4 μg/mL; EPI = epinephrine; LTA = light transmission aggregometry; RIST = ristocetine; TRAP = thrombin receptor activating peptide.

Fig 2. Level of fibrinogen (g/L) in children and adults using valproic acid.

The bars represent the mean value and standard variation. Mean values did not differ significantly (p-value 0.283).

Fig 3

a. Graph of the platelet count (x 10⁹/L) in patients in the low dosage (0.1–20 mg/kg/day) and high dosage (>20 mg/kg/day) valproic acid (VPA) group. Bars are representing the mean value and standard deviation. Mean values did not differ significantly (p-value 0.064). b. Scatter plot of the dosage VPA (mg/kg/day) versus the platelet count (x 10 /L) (Pearson’s ρ 0.015, p-value 0.901).