Woolley S, Burger H R, Zellweger U
Medizinische Abteilung des Regionalspitals Ilanz.
Dtsch Med Wochenschr. 1995 Nov 3;120(44):1507-10. doi: 10.1055/s-2008-1055506.
A 78-year-old woman had 4 years age received phenprocoumon as prophylaxis against thromboembolism after implantation of a left total knee prosthesis. Ten weeks later she developed hepatitis with negative hepatitis serology. 6 weeks before her latest hospitalisation a right total knee implantation had been performed and she again received phenprocoumon. She was admitted now because of cholestatic jaundice with rapid deterioration of her general state. There were no significant abnormal findings other than jaundiced skin and sclerae.
Bilirubin concentration was clearly elevated to 11.5 mg/dl, and the transaminase activities were increased, together with raised gamma-GT and alkaline phosphatase levels. The Quick value was below 8%. Hepatitis serology was positive for hepatitis A antibodies, but negative for B and C antibodies. No antigens were demonstrated. The eosinophil count was elevated in the differential blood count. Sonography showed a normal-sized liver with slightly dense echo pattern, but no evidence of abscess or dilatation of the bile duct system. Liver biopsy revealed severe acute hepatitis of viral type and discrete eosinophilic infiltration.
After all medication had been discontinued, transaminase activities decreased while bilirubin concentration rose. Thus, prednisone treatment was started (initially 50 mg/d), the dose then gradually reduced. The cholestasis parameters became normal and the patient's general state was much improved so that she could be discharged.
Cholestatic hepatitis is a rare side effect of phenprocoumon. The associated eosinophilia suggests the cause to be an allergic genesis in the sense of a hypersensitivity reaction.
一名78岁女性在4年前因左全膝关节置换术后接受苯丙香豆素预防血栓栓塞。10周后，她出现肝炎，肝炎血清学检查呈阴性。在她最近一次住院前6周，进行了右全膝关节置换术，她再次接受了苯丙香豆素治疗。她因胆汁淤积性黄疸伴全身状况迅速恶化而入院。除皮肤和巩膜黄疸外，无明显异常发现。
胆红素浓度明显升高至11.5mg/dl，转氨酶活性增加，γ-谷氨酰转移酶和碱性磷酸酶水平也升高。凝血酶原时间（Quick值）低于8%。肝炎血清学检查甲型肝炎抗体呈阳性，但乙型和丙型肝炎抗体呈阴性。未检测到抗原。血常规分类计数中嗜酸性粒细胞计数升高。超声检查显示肝脏大小正常，回声略密集，但未发现脓肿或胆管系统扩张的迹象。肝活检显示为严重的急性病毒性肝炎和散在的嗜酸性粒细胞浸润。
停用所有药物后，转氨酶活性下降而胆红素浓度上升。因此，开始使用泼尼松治疗（初始剂量为50mg/d），随后逐渐减量。胆汁淤积参数恢复正常，患者的全身状况明显改善，得以出院。
胆汁淤积性肝炎是苯丙香豆素罕见的副作用。相关的嗜酸性粒细胞增多提示病因是超敏反应意义上的过敏反应。
