Valproic acid-associated low fibrinogen and delayed intracranial hemorrhage: case report and mini literature review
A 41-year-old male had suffered from gradual hearing loss in his right ear for 2 years. Head computed tomography and magnetic resonance imaging scans showed a neoplasm in the cerebellopontine angle region, which was suspected to be acoustic neurilemmoma. Preoperative routine coagulation tests of APTT, PT, thrombin time, Fbg, and platelet count (Plt) were within the normal ranges, and he had no history of bleeding since birth. Clinical examination, biochemistry analysis, and kidney function were normal. The echocardiogram showed normal sinus rhythm. The patient had a history of hepatitis B 20 years before; however, liver enzymes and synthesis function were normal before surgery.\nResection of the neoplasm was successfully performed and blood loss was not excessive during the operation. The results of the pathological examination confirmed the diagnosis of acoustic neurilemmoma. VPA was administered at 20 mg/kg/day to prevent seizures after surgery. Twelve days after surgery, the patient reported headache and examination suggested suspected re-bleeding from the surgical site. This was confirmed in the second surgery. He was treated by decompressive craniotomy to relieve the high pressure.\nAfter the second surgery, a drainage tube was inserted in the incision, since interim bleeding was present (). He received daily transfusions of fresh plasma and cryoprecipitate to improve coagulation function, but the volume of drainage from surgical lesions remained about 30 mL/d. His coagulation function was again tested and he was found to have normal PT, APTT, TT, D-dimer, coagulation factors, and Plt, but a low Fbg level (0.8–1.6 g/L; reference value, 2–4 g/L), high tissue-type plasminogen activator (t-PA) activity (5,400 U/mL; reference value, 300–600 U/mL), and high fibrinogen/fibrin degradation product (FDP) level (60 mg/L; reference value, <10 mg/L). Meanwhile, his biochemistry results, kidney function, and liver function remained normal.\nThe patient was referred to the Department of Hematology for further management on 30 days following his first surgery. With a supplement of daily Fbg (3 g/d) and use of antifibrinolytic agents for 5 days, the amount of bleeding from the drainage tube decreased gradually and the patient felt his headache relieved without VPA. Coagulation was tested daily and results showed that the Fbg gradually returned to normal within 5 days: from 0.8 g/L on the first day to 1.2 g/L on the second day of treatment, 1.8 g/L on the third day, 2.3 g/L on the fourth day, and 3.5 g/L on the fifth. Coagulation parameters were maintained at normal levels in a week without Fbg transfusion.\nFollowing this, the patient was referred again to the Department of Neurosurgery and VPA treatment was resumed. Amazingly, his Fbg level decreased over time, reaching the minimum level of 0.53 g/L on the fifth day of VPA re-administration. Fortunately, the patient had no bleeding symptoms or manifestation. VPA-associated hypofibrinogenemia was suspected, so the treatment discontinued. Following this, his Fbg level returned to normal and remained stable. The drainage tube was removed 61 days after his first surgery. At follow-up at 6 months, the patient’s hemostatic parameters including Fbg were normal and no symptoms of bleeding were found.