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Sequential therapy with activated prothrombin complex concentrate (FEIBA) and recombinant factor VIIa in a patient with severe haemophilia A, inhibitor presence and refractory bleeding

Patients with haemophilia A are at risk for developing inhibitors which render conventional factor replacement therapy ineffective. In such cases, bypassing the inhibitor is required to achieve haemostasis. Both activated prothrombin complex concentrates (aPCC) and recombinant factor VIIa (rVIIa) have demonstrated efficacy in treating bleeds in patients with inhibitor presence [1,2]. However, clinical response may be variable between patients or between bleeding episodes and, in some cases, either therapeutic intervention may fail. Sequential use of multiple bypassing agents has been shown in vitro to provide a mechanism to increase efficacy but has not met with wide clinical use because of concern regarding the possibility of thrombosis [3]. The present case report concerns a 13-year-old boy with severe haemophilia A, haemophilic arthropathy and inhibitor presence not responding to previous therapy with retuximab. The patient was admitted to the paediatric surgery department because of abdominal pain, with a possible diagnosis of acute appendicitis. He underwent surgery, receiving rVIIa (90 lg kg) prior to and following operation, however, diagnosis of appendicitis was not confirmed in the operating room. Laboratory work up on admission was as follows: Hb 12.6 g dL, WBC 14 300 mm [3] (63% neutropohils), PLT 559 000 mm and FVIII antibody titre 6 BU. Postoperatively, the patient presented with severe haematuria and rectum bleeding. Despite continuous treatment with rVIIa (90 lg kg every 2 h), bleeding persisted. On the fifth postoperative day laboratory examination showed: aPTT 63.6¢¢/31¢¢, INR 0.67, fibrinogen 201 mg dL, D-dimers > 1000 mg L. The haemoglobin level dropped to 5.6 g dL, the patient requiring multiple packed red cell transfusions. CT scan revealed multiple blood collections: in the chest (haemothorax), around the liver and spleen, in the small pelvis, in the small and large intestine, in the left kidney and the right perinephral area (Figs 1 and 2). Still on monotherapy with rFVII, the patient was transferred to the paediatric department on the 10th postoperative day where, because of refractory bleeding, a combined bypassing agent therapy was decided. The initial regimen consisted of 90 lg kg of rFVIIa given two hourly and 50 U kg of Factor