The hematologic consequences of novel Anti-seizure medications (ASMs) are rarely reported.

Whether coagulation dysfunctions increase the risk of peri-operative bleeding remains controversial.

The research is performed to investigated the incidence and risk factors of preoperative coagulation dysfunction in children undergoing surgery for epilepsy and their impact on surgery.

Epilepsy is a common disease of the nervous system with severe consequences. Epidemiological surveys have shown that the prevalence of epilepsy in China is approximately 0.4-0.7%, comprising 7-10 million patients with epilepsy, most of whom are children. Although most symptoms of epilepsy can be controlled with the use of anti-seizure medications (ASMs), there are still a few patients who cannot achieve satisfactory seizure control with such medications or cannot tolerate their side effects, thus requiring surgical treatment. Surgical treatment of epilepsy has been recognized as a valuable treatment option for carefully selected patients to achieve better seizure control and quality of life. Compared to adults, children with epilepsy with indications for surgery usually have a better prognosis after surgical treatment. Many children undergoing surgery for epilepsy have a long history of using ASMs. Moreover, ASM therapy usually consists of multiple varieties of drugs, thereby bringing significant attention to the side effects of ASMs, especially those that may be relevant in the perioperative surgical setting.

ASMs have been associated with multiple adverse effects on platelets and the coagulation system. Valproic acid (VPA), one of the most commonly used traditional ASM, has been reported to cause multiple hematologic abnormalities, including thrombocytopenia, platelet aggregation dysfunction, fibrinogen (FBG) depletion, bone marrow suppression, decreased factor XIII, and acquired von Willebrand disease. However, the wide use of novel ASMs in recent decades has led to decreased reports of adverse events. The hematologic consequences of these novel ASMs or combined therapies are rarely reported. Few studies have suggested that levetiracetam (LEV) does not cause clinically significant or relevant hematological disorders.

Such reported side effects may be more significant in pediatric patients with epilepsy due to individual differences in age, weight, and pharmacokinetic action of the body on the drugs. The incidence of coagulopathies has been reported to be higher in children than in adults, especially hypofibrinogenemia. Nevertheless, whether these coagulation dysfunctions increase the risk of peri-operative bleeding remains controversial. Most investigators suggest that ASMs, including VPA, are not associated with surgery-related blood loss or transfusion requirements. However, a few studies have suggested that considering the extra risk of peri-operative bleeding, VPA should be discontinued before surgery.

This retrospective analysis of 390 children with epilepsy systematically investigated the incidence and risk factors of preoperative coagulation dysfunction in children undergoing surgery for epilepsy and their impact on surgery, with the objective to provide detailed and valuable clinical information.

Inclusion Criteria:

• Age<18 years
• A discharge diagnosis of "epilepsy" according to the International Classification of Diseases (ICD-10)
• Received surgical treatment for epilepsy during the hospitalization
• Hospitalized between January 2015 and December 2021 at the Neurosurgery Department of Children's Hospital of Fudan University
• Non-epileptic children who underwent non-epilepsy neurological surgery by the same surgeon and were admitted at the same period for control

Exclusion Criteria:

• The clinical information or laboratory examinations were incomplete
• Had concomitant diseases affecting coagulation or liver function
• Patients or parents refused to be enrolled

The study population were children who were hospitalized between January 2015 and December 2021 at the Neurosurgery Department of Children's Hospital of Fudan University, including non-epileptic children who underwent non-epilepsy neurological surgery by the same surgeon and were admitted at the same period for control.

• 319 patients with epilepsy who administered Anti-seizure Medications (ASMs);
• 71 patients with epilepsy who were not administered ASMs;
• 104 non-epileptic children who underwent neurosurgical operations and had never taken any ASMs.

According to the Ethic Board of Children's Hospital of Fudan University, the clinical data of patients could not been shared without permission.