Successful management of Mallory‐Weiss syndrome in a haemophilia A patient with inhibitor by recombinant activated factor VII

Abstract

The development of factor VIII (FVIII) inhibitors is the most serious clinical complication in the replacement therapy with FVIII concentrates for haemophilia A patients. Except for the case with low responding inhibitor, the main haemostatic treatment for acute bleeding is a bypassing therapy with either activated prothrombin complex concentrates (APCCs) or recombinant activated factor VII (rFVIIa). Upper gastrointestinal (GI) tract haemorrhage is not rare and is life-threatening in some cases because of massive bleeding. In such cases, effective bypassing therapy should be initiated immediately. However, there are few practical guidelines and recommendations for the bypassing therapy in such a severe bleeding from upper GI tract. Mallory-Weiss syndrome is a relatively rare bleeding condition in patients with haemophilia, characterized by bleeding from tears in the mucosa at the junction of the stomach and oesophagus, resulting from abrupt increase of intraperitoneal pressure usually caused by severe coughing or vomiting. The syndrome is often associated with a history of heavy alcohol use [1]. Hiatal hernia and ageing have been reported as predisposing factors [2]. In this report, we present a young haemophilia A patient with inhibitor in whom Mallory-Weiss syndrome occurred without any trigger, history of alcohol consumption or cirrhosis. A 21-year-old haemophilia A patient with hightitre inhibitor presented nausea and vomiting without blood in the evening of September 5, 2007. As the patient had developed inhibitor at 7 years of age, he had been treated with APCC. Afterwards, immune tolerance induction therapy was provided but without success. The patient had received regular infusion of rFVIIa (94 lg kg thrice weekly) because of frequent episodes of joint bleeding. The following morning, a tarry stool developed. As hematemesis developed in the evening, the patient was admitted to Akashi Municipal Hospital with the clinical diagnosis of upper GI haemorrhage. His body weight was 51.0 kg. Physical findings at admission were not remarkable and digestive symptoms such as vomiting and haematochezia were not significant. Haemoglobin level was 12.0 g dL on admission, suggesting blood loss from GI tract was mild. The patient had no history of alcohol consumption, liver cirrhosis, or viral hepatitis. Bolus infusion of rFVIIa was administered at the dose of 6.0 mg (118 lg kg). Famotidine, a histamine H2-receptor antagonist, was also given intravenously. Furthermore, to be on a safer side, FEIBA (3000 U) was administered twice, at midnight and on the next morning as it was still possible that rFVIIa had not been enough to restrain upper GI haemorrhage. The patient complained of no nausea or abdominal pain during this time, which indicated that the haemostatic therapy was effective. Oral ingestion was started from the noon meal on the following day. However, bloody vomit developed again in the late afternoon and a blood test revealed progressive anaemia (Hb 8.2 g dL). The history of initial vomiting of non-bloody emesis followed by recurrent episodes of hematemesis was suggestive of Mallory-Weiss syndrome. Emergency endoscopy of the upper GI tract revealed haemorrhage at gastro-oesophageal junction, which led to the diagnosis of Mallory-Weiss syndrome (Fig. 1 left). Two Correspondence: Yoshihiko Sakurai, MD, PhD, Department of Pediatrics, Nara Medical University School of Medicine, 840 Shijo-cho, Kashihara, Nara 634-8522, Japan. Tel.: +81 744 29 8881; fax: +81 744 24 9222; e-mail: ysakurai@naramed-u.ac.jp